Disruption of normal circadian clock function in a mouse model of tauopathy.
Abstract Disruption of normal circadian rhythm physiology is associated with neurodegenerative disease. In Alzheimer's disease (AD), circadian dysfunction has been attributed to β-amyloidosis. However, it is presently unclear whether tauopathy, another AD-associated neuropathology, also contributes to the disruption of normal circadian clock function. We demonstrate changes in normal circadian clock function in a transgenic mouse model of tauopathy (Tg4510) through assessment of both molecular and behavioral rhythms. We show that Tg4510 mice display a long free-running period at an age when tauopathy is prese...
Source: Experimental Neurology - April 28, 2017 Category: Neurology Authors: Stevanovic K, Yunus A, Joly-Amado A, Gordon M, Morgan D, Gulick D, Gamsby J Tags: Exp Neurol Source Type: research

Refining environmental enrichment to advance rehabilitation based research after experimental traumatic brain injury.
Abstract The typical environmental enrichment (EE) paradigm, which consists of continuous exposure after experimental traumatic brain injury (TBI), promotes behavioral and histological benefits. However, rehabilitation is often abbreviated in the clinic and administered in multiple daily sessions. While recent studies have demonstrated that a once daily 6-hr bout of EE confers benefits comparable to continuous EE, breaking the therapy into two shorter sessions may increase novelty and ultimately enhance recovery. Hence, the aim of the study was to test the hypothesis that functional and histological outcomes will ...
Source: Experimental Neurology - April 27, 2017 Category: Neurology Authors: Radabaugh HL, LaPorte MJ, Greene AM, Bondi CO, Lajud N, Kline AE Tags: Exp Neurol Source Type: research

Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.
ister S Abstract Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14days the ra...
Source: Experimental Neurology - April 27, 2017 Category: Neurology Authors: Ücal M, Haindl MT, Adzemovic MZ, Strasser J, Theisl L, Zeitelhofer M, Kraitsy K, Ropele S, Schäfer U, Fazekas F, Hochmeister S Tags: Exp Neurol Source Type: research

Maternal IL-17A in autism.
Abstract Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental factors. Immune dysregulation has gained significant attention as a causal mechanism in ASD pathogenesis. ASD has been associated with immune abnormalities in the brain and periphery, including inflammatory disorders and autoimmunity in not only the affected individuals but also their mothers. Prenatal exposure to maternal immune activation (MIA) has been implicated as an environmental risk factor for ASD. In support of this notion, animal...
Source: Experimental Neurology - April 25, 2017 Category: Neurology Authors: Wong H, Hoeffer C Tags: Exp Neurol Source Type: research

Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion.
a ALR Abstract Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESCs/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal surv...
Source: Experimental Neurology - April 24, 2017 Category: Neurology Authors: Araújo MR, Kyrylenko S, Spejo AB, de Castro MV, Junior RSF, Barraviera B, de Oliveira ALR Tags: Exp Neurol Source Type: research

The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury.
Abstract Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI. To test this hypothesis,...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Stivers NS, Pelisch N, Orem BC, Williams J, Nally JM, Stirling DP Tags: Exp Neurol Source Type: research

Altered somatosensory cortex neuronal activity in a rat model of Parkinson's disease and levodopa-induced dyskinesias.
In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under urethane (1.4g/kg, i.p.) anesthesia. Further, gene expression patterns of distinct markers for inhibitory GABAergic neurons were analyzed in both cortical regions. While firing frequency and burst activity of S1FL-Ctx inhibitory i...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Alam M, Rumpel R, Jin X, von Wrangel C, Tschirner S, Krauss JK, Grothe C, Ratzka A, Schwabe K Tags: Exp Neurol Source Type: research

Trumping neurodegeneration: Targeting common pathways regulated by autosomal recessive Parkinson's disease genes.
Abstract Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis. Understanding how aber...
Source: Experimental Neurology - April 23, 2017 Category: Neurology Authors: Scott L, Dawson VL, Dawson TM Tags: Exp Neurol Source Type: research

Worms on the spectrum - C. elegans models in autism research.
Abstract The small non-parasitic nematode Caenorhabditis elegans is widely used in neuroscience thanks to its well-understood development and lineage of the nervous system. Furthermore, C. elegans has been used to model many human developmental and neurological conditions to better understand disease mechanisms and identify potential therapeutic strategies. Autism spectrum disorder (ASD) is the most prevalent of all neurodevelopmental disorders, and the C. elegans system may provide opportunities to learn more about this complex disorder. Along with a repertoire of behaviours, since basic cell biology and biochemi...
Source: Experimental Neurology - April 20, 2017 Category: Neurology Authors: Schmeisser K, Alex Parker J Tags: Exp Neurol Source Type: research

Supraspinal respiratory plasticity following acute cervical spinal cord injury.
Abstract Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm - a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks. Although many studies have shown such plasticity at the level of the spinal cor...
Source: Experimental Neurology - April 19, 2017 Category: Neurology Authors: Bezdudnaya T, Marchenko V, Zholudeva LV, Spruance VM, Lane MA Tags: Exp Neurol Source Type: research

Role of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson's disease model.
Abstract A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40days after PD-induction. The functional deficiency is restored 60days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before, and then 40 and 60days after bilateral 6-OHDA (24&mu...
Source: Experimental Neurology - April 18, 2017 Category: Neurology Authors: Oliveira LM, Tuppy M, Moreira TS, Takakura AC Tags: Exp Neurol Source Type: research

Mice with conditional NeuroD1 knockout display reduced aberrant hippocampal neurogenesis but no change in epileptic seizures.
Abstract Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiat...
Source: Experimental Neurology - April 18, 2017 Category: Neurology Authors: Brulet R, Zhu J, Aktar M, Hsieh J, Cho KO Tags: Exp Neurol Source Type: research

Inflammation-induced GluA1 trafficking and membrane insertion of Ca(2+) permeable AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis factor, PI3 kinase and protein kinase A.
Abstract Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls. In the same tissue, GluA...
Source: Experimental Neurology - April 12, 2017 Category: Neurology Authors: Wigerblad G, Huie JR, Yin HZ, Leinders M, Pritchard RA, Koehrn FJ, Xiao WH, Bennett GJ, Huganir RL, Ferguson AR, Weiss JH, Svensson CI, Sorkin LS Tags: Exp Neurol Source Type: research

Hypersociability in the Angelman syndrome mouse model.
We report that mice with maternally-inherited Ube3a gene deletion (Ube3a(mKO)) have a prolonged preference for, and interaction with, social stimuli in the three chamber social approach task. By contrast, interactions with a novel object are reduced. Further, ultrasonic vocalizations and physical contacts are increased in male and female Ube3a(mKO) mice paired with an unfamiliar genotype-matched female. Single housing wild type mice increased these same social behavior parameters to levels observed in Ube3a(mKO) mice where this effect was partially occluded. These results indicate sociability is repressed by social experie...
Source: Experimental Neurology - April 11, 2017 Category: Neurology Authors: Stoppel DC, Anderson MP Tags: Exp Neurol Source Type: research

Human stem cell modeling in neurofibromatosis type 1 (NF1).
Abstract The future of precision medicine is heavily reliant on the use of human tissues to identify the key determinants that account for differences between individuals with the same disorder. This need is exemplified by the neurofibromatosis type 1 (NF1) neurogenetic condition. As such, individuals with NF1 are born with a germline mutation in the NF1 gene, but may develop numerous distinct neurological problems, ranging from autism and attention deficit to brain and peripheral nerve sheath tumors. Coupled with accurate preclinical mouse models, the availability of NF1 patient-derived induced pluripotent stem c...
Source: Experimental Neurology - April 6, 2017 Category: Neurology Authors: Wegscheid ML, Anastasaki C, Gutmann DH Tags: Exp Neurol Source Type: research

A rapid chemical-genetic screen utilizing impaired movement phenotypes in C. elegans: Input into genetics of neurodevelopmental disorders.
In this study, we present a screening approach of potential C. elegans mutants as potential ASD models. We screened these mutants for motor-deficiency phenotypes, which can be exploited to study underlying mechanisms of the disorder. Selected motor-deficient mutants were then used in a comprehensive drug screen of over 3900 compounds, including many FDA-approved and natural molecules, that were analyzed for their ability to suppress motility defects caused by ASD-associated gene orthologues. This genetic-chemical approach, i.e. establishing C. elegans models for ASD and screening of a well-characterized compound library, m...
Source: Experimental Neurology - March 31, 2017 Category: Neurology Authors: Schmeisser K, Fardghassemi Y, Alex Parker J Tags: Exp Neurol Source Type: research

Early-life febrile seizures worsen adult phenotypes in Scn1a mutants.
Abstract Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Nav1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS). Patients with SCN1A mutations often experience prolonged early-life febrile seizures (FSs), raising the possibility that these events may influence epileptogenesis and lead to more severe adult phenotypes. To test this hypothesis, we subjected 21-23-day-old mice expressing the human SCN1A GEFS+ mutation R1648H to prolonged hyperthermia, and then examined seizure and behavioral...
Source: Experimental Neurology - March 31, 2017 Category: Neurology Authors: Dutton SB, Dutt K, Papale LA, Helmers S, Goldin AL, Escayg A Tags: Exp Neurol Source Type: research

Pioglitazone treatment following spinal cord injury maintains acute mitochondrial integrity and increases chronic tissue sparing and functional recovery.
Abstract Pioglitazone is an FDA-approved PPAR-γ agonist drug used to treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice. Mice received either vehicle or pioglitazo...
Source: Experimental Neurology - March 30, 2017 Category: Neurology Authors: Patel SP, Cox DH, Gollihue JL, Bailey WM, Geldenhuys WJ, Gensel JC, Sullivan PG, Rabchevsky AG Tags: Exp Neurol Source Type: research

Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.
Abstract Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde ...
Source: Experimental Neurology - March 30, 2017 Category: Neurology Authors: Saito H, Katagiri A, Okada S, Mikuzuki L, Kubo A, Suzuki T, Ohara K, Lee J, Gionhaku N, Iinuma T, Bereiter DA, Iwata K Tags: Exp Neurol Source Type: research

Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast.
Abstract Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal sli...
Source: Experimental Neurology - March 30, 2017 Category: Neurology Authors: Vogel EW, Morales FN, Meaney DF, Bass CR, Morrison B Tags: Exp Neurol Source Type: research

TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.
CONCLUSIONS: TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats. PMID: 28365474 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 29, 2017 Category: Neurology Authors: Ma XD, Hang LH, Shao DH, Shu WW, Hu XL, Luo H Tags: Exp Neurol Source Type: research

2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington's disease.
In this study, we evaluated the effects of chronic administration of DNP at three doses (0.5, 1, 5mg/kg/day) on mHtt-induced behavioral deficits and cellular abnormalities in the N171-82Q HD mouse model. DNP at a low dose (1mg/kg/day) significantly improved motor function and preserved medium spiny neuronal marker DARPP32 and postsynaptic protein PSD95 in the striatum of HD mice. Further mechanistic study suggests that DNP at this dose reduced oxidative stress in HD mice, which was indicated by reduced levels of F2-isoprostanes in the brain of HD mice treated with DNP. Our data indicated that DNP provided behavioral benefi...
Source: Experimental Neurology - March 27, 2017 Category: Neurology Authors: Wu B, Jiang M, Qi P, Li G, Hou Z, Milne GL, Mori S, Alonso R, Geisler JG, Duan W Tags: Exp Neurol Source Type: research

Bilateral tactile hypersensitivity and neuroimmune responses after spared nerve injury in mice lacking vasoactive intestinal peptide.
Abstract Vasoactive intestinal peptide (VIP) is one of the neuropeptides showing the strongest up-regulation in the nociceptive pathway after peripheral nerve injury and has been proposed to support neuropathic pain. Nevertheless, the story may be more complicated considering the known suppressive effects of the peptide on the immune reactivity of microglial cells, which have been heavily implicated in the onset and maintenance of pain after nerve injury. We here used mice deficient in VIP and the model of spared nerve injury, characterized by persistent tactile hypersensitivity. While tactile hypersensitivity dev...
Source: Experimental Neurology - March 27, 2017 Category: Neurology Authors: Gallo A, Leerink M, Michot B, Ahmed E, Forget P, Mouraux A, Hermans E, Deumens R Tags: Exp Neurol Source Type: research

A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
oni P Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 ALS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology. We...
Source: Experimental Neurology - March 25, 2017 Category: Neurology Authors: Marcuzzo S, Bonanno S, Figini M, Scotti A, Zucca I, Minati L, Riva N, Domi T, Fossaghi A, Quattrini A, Galbardi B, D'Alessandro S, Bruzzone MG, García-Verdugo JM, Moreno-Manzano V, Mantegazza R, Bernasconi P Tags: Exp Neurol Source Type: research

BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section.
Abstract Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was...
Source: Experimental Neurology - March 24, 2017 Category: Neurology Authors: Meng L, Huang T, Sun C, Hill DL, Krimm R Tags: Exp Neurol Source Type: research

Spinal cord injury in hypertonic newborns after antenatal hypoxia-ischemia in a rabbit model of cerebral palsy.
This study examined whether hypertonia in rabbits was accompanied by changes in spinal architecture. Rabbit dams underwent global fetal H-I at embryonic day 25 for 40min. High resolution diffusion tensor imaging was performed on fixed neonatal CNS. Fractional anisotropy (FA) and regional volumetric measurements were compared between kits with and without hypertonia after H-I and sham controls using Tract Based Spatial Statistics. Hypertonic kits showed evidence of damage from hypoxia not only in the brain, but in spinal cord as well. Hypertonic kits showed reduced FA and thickness in corticospinal tracts, external capsule,...
Source: Experimental Neurology - March 24, 2017 Category: Neurology Authors: Drobyshevsky A, Quinlan KA Tags: Exp Neurol Source Type: research

Subthalamic nucleus beta and gamma activity is modulated depending on the level of imagined grip force.
Abstract Motor imagery involves cortical networks similar to those activated by real movements, but the extent to which the basal ganglia are recruited is not yet clear. Gamma and beta oscillations in the subthalamic nucleus (STN) vary with the effort of sustained muscle activity. We recorded local field potentials in Parkinson's disease patients and investigated if similar changes can be observed during imagined gripping at three different 'forces'. We found that beta activity decreased significantly only for imagined grips at the two stronger force levels. Additionally, gamma power significantly scaled with incr...
Source: Experimental Neurology - March 22, 2017 Category: Neurology Authors: Fischer P, Pogosyan A, Cheeran B, Green AL, Aziz TZ, Hyam J, Little S, Foltynie T, Limousin P, Zrinzo L, Hariz M, Samuel M, Ashkan K, Brown P, Tan H Tags: Exp Neurol Source Type: research

RNAi of arcRNA hsr ω affects sub-cellular localization of Drosophila FUS to drive neurodiseases.
RNAi of arcRNA hsrω affects sub-cellular localization of Drosophila FUS to drive neurodiseases. Exp Neurol. 2017 Mar 22;: Authors: Piccolo LL, Yamaguchi M Abstract Defective RNA metabolism is common pathogenic mechanisms involved in neurological disorders. Indeed, a conspicuous feature of some neurodegenerative diseases is the loss of nuclear activities of RNA-binding proteins (RBPs) like Fused in sarcoma (FUS) and eventually, their accumulation in cytoplasmic proteinaceous inclusions. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes,...
Source: Experimental Neurology - March 22, 2017 Category: Neurology Authors: Piccolo LL, Yamaguchi M Tags: Exp Neurol Source Type: research

Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia.
Abstract l-DOPA remains the benchmark treatment for Parkinson's disease (PD) motor symptoms, but chronic use leads to l-DOPA-induced dyskinesia (LID). The serotonin (5-HT) system has been established as a key modulator of LID and 5-HT1A receptors (5-HT1AR) stimulation has been shown to convey anti-dyskinetic effects. However, 5-HT1AR agonists often compromise clinical efficacy or display intrinsic side effects and their site(s) of actions remain debatable. Recently, highly selective G-protein biased 5-HT1AR agonists, F13714 and F15599, were shown to potently target 5-HT1A auto- or hetero-receptors, respectively. T...
Source: Experimental Neurology - March 22, 2017 Category: Neurology Authors: Meadows SM, Chambers N, Conti MM, Bossert SC, Tasber C, Sheena E, Varney M, Newman-Tancredi A, Bishop C Tags: Exp Neurol Source Type: research

Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.
Abstract Downregulation in the astroglial glutamate transporter EAAT2 in amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 mouse models of ALS is believed to contribute to the death of motor neurons by excitotoxicity. We previously reported that caspase-3 cleaves EAAT2 at a unique cleavage consensus site located in its c-terminus domain, a proteolytic cleavage that also occurs in vivo in the mutant SOD1 mouse model of ALS and leads to accumulation of a sumoylated EAAT2 C-Terminus fragment (CTE-SUMO1) beginning around onset of disease. CTE-SUMO1 accumulates in PML nuclear bodies of astrocytes and causes ...
Source: Experimental Neurology - March 22, 2017 Category: Neurology Authors: Rosenblum LT, Shamamandri-Markandaiah S, Ghosh B, Foran E, Lepore AC, Pasinelli P, Trotti D Tags: Exp Neurol Source Type: research

Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion.
Abstract A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid-induced 1) increases in norepinephrine (NE) release in the medial prefrontal cortex (mPFC); 2) desensitization of cortical α2-adrenoceptor-mediated effects; 3) activation of c-Fos in brainstem locus coeruleus (LC) noradrenergic neurons; and 4) increases in anxiety-like behaviors. In the present study, we soug...
Source: Experimental Neurology - March 21, 2017 Category: Neurology Authors: Reyes BA, Carvalho AF, Szot P, Kalamarides DJ, Wang Q, Kirby LG, Van Bockstaele EJ Tags: Exp Neurol Source Type: research

Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats.
Abstract Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2weeks) and then either left untrained or step...
Source: Experimental Neurology - March 21, 2017 Category: Neurology Authors: Chen K, Marsh BC, Cowan M, Al'Joboori YD, Gigout S, Smith CC, Messenger N, Gamper N, Schwab ME, Ichiyama RM Tags: Exp Neurol Source Type: research

Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.
This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. PMID: 28336394 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 20, 2017 Category: Neurology Authors: Shimohata A, Ishihara K, Hattori S, Miyamoto H, Morishita H, Ornthanalai G, Raveau M, Ebrahim AS, Amano K, Yamada K, Sago H, Akiba S, Mataga N, Murphy NP, Miyakawa T, Yamakawa K Tags: Exp Neurol Source Type: research

Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD1 mouse model of amyotrophic lateral sclerosis.
an CF Abstract Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects upper and lower motoneurones. The underlying pathophysiology of the disease is complex but electrophysiological studies of peripheral nerves in ALS patients as well as human autopsy studies indicate that a potassium channel dysfunction/loss is present early in the symptomatic phase. It remains unclear to what extent potassium channel abnormalities reflect a specific pathogenic mechanism in ALS. The aim of this study was therefore to investigate the temporal changes in the expression and/or function o...
Source: Experimental Neurology - March 16, 2017 Category: Neurology Authors: Maglemose R, Hedegaard A, Lehnhoff J, Dimintiyanova KP, Moldovan M, Grøndahl L, Meehan CF Tags: Exp Neurol Source Type: research

Corrigendum to "Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons" (Exp. Neurol. 289, Pages 31-45).
Corrigendum to "Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons" (Exp. Neurol. 289, Pages 31-45). Exp Neurol. 2017 Mar 12;: Authors: Bodrikov V, Pauschert A, Kochlamazashvili G, Stuermer CA PMID: 28292530 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 12, 2017 Category: Neurology Authors: Bodrikov V, Pauschert A, Kochlamazashvili G, Stuermer CA Tags: Exp Neurol Source Type: research

Corrigendum to "Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus" [Exp. Neurol. 271 (2015) 319-328].
Corrigendum to "Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus" [Exp. Neurol. 271 (2015) 319-328]. Exp Neurol. 2017 Mar 11;: Authors: Ortiz F, Gutiérrez R PMID: 28291520 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 11, 2017 Category: Neurology Authors: Ortiz F, Gutiérrez R Tags: Exp Neurol Source Type: research

Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.
In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rC...
Source: Experimental Neurology - March 8, 2017 Category: Neurology Authors: Bimpisidis Z, M Öberg C, Maslava N, Cenci MA, Lundblad C Tags: Exp Neurol Source Type: research

Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.
Abstract Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific m...
Source: Experimental Neurology - March 7, 2017 Category: Neurology Authors: Pan M, Wang X, Chen Y, Cao S, Wen J, Wu G, Li Y, Li L, Qian C, Qin Z, Li Z, Tan D, Fan Z, Wu W, Guo J Tags: Exp Neurol Source Type: research

Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse.
In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro dat...
Source: Experimental Neurology - March 6, 2017 Category: Neurology Authors: Ye X, Shen T, Hu J, Zhang L, Zhang Y, Bao L, Cui C, Jin G, Zan K, Zhang Z, Yang X, Shi H, Zu J, Yu M, Song C, Wang Y, Qi S, Cui G Tags: Exp Neurol Source Type: research

Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration).
The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7J, and post-TBI outcomes were assessed over an acute period of 14days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astroglios...
Source: Experimental Neurology - March 5, 2017 Category: Neurology Authors: Namjoshi DR, Cheng WH, Bashir A, Wilkinson A, Stukas S, Martens KM, Whyte T, Abebe ZA, McInnes KA, Cripton PA, Wellington CL Tags: Exp Neurol Source Type: research

Diabetic aggravation of stroke and animal models.
Abstract Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia...
Source: Experimental Neurology - March 5, 2017 Category: Neurology Authors: Rehni AK, Liu A, Perez-Pinzon MA, Dave KR Tags: Exp Neurol Source Type: research

Inhibition of Drp1 hyper-activation is protective in animal models of experimental multiple sclerosis.
Abstract Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and...
Source: Experimental Neurology - February 23, 2017 Category: Neurology Authors: Luo F, Herrup K, Qi X, Yang Y Tags: Exp Neurol Source Type: research

Asymmetric dopaminergic degeneration and levodopa alter functional corticostriatal connectivity bilaterally in experimental parkinsonism.
Abstract Asymmetric dopamine loss is commonly found in early Parkinson's disease (PD), but its effects on functional networks have been difficult to delineate in PD patients because of variations in age, disease duration and therapy. Here we used unilateral 6-hydroxydopamine-lesioned (6-OHDA) rats and controls and treated them with a single intraperitoneal injection of levodopa (L-DOPA) before performing diffusion weighted MRI and resting state functional MRI (rs-fMRI). In accordance with a neurodegeneration of the nigrostriatal dopaminergic pathway, diffusion tensor imaging showed increased radial diffusivity and...
Source: Experimental Neurology - February 18, 2017 Category: Neurology Authors: Monnot C, Zhang X, Nikkhou-Aski S, Damberg P, Svenningsson P Tags: Exp Neurol Source Type: research

Nanoconjugate-bound adenosine A1 receptor antagonist enhances recovery of breathing following acute cervical spinal cord injury.
The objective of the present study was to test the hypothesis that intradiaphragmatic administration of nanoconjugate-bound DPCPX, enhances recovery of ventilation following SCI in the unanesthetized rat. To that end, Sprague-Dawley rats underwent C2 spinal cord hemisection (C2Hx) on day 0 and received either: (i) 0.15μg/kg of nanoconjugate-bound DPCPX or (ii) vehicle control (50μl distilled water). To assess ventilation, unrestrained whole body plethysmography (WBP) was performed on day 0 (immediately before the surgery) and 3, 7, 14, 21 and 28days following the SCI. Frequency, tidal volume, and minute ventilation d...
Source: Experimental Neurology - February 18, 2017 Category: Neurology Authors: Minic Z, Wilson S, Liu F, Sankari A, Mao G, Goshgarian H Tags: Exp Neurol Source Type: research

Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy.
Abstract The molecular determinants of pathogenic leukocyte migration across the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are unknown. Specific disease modifying therapies for CIDP are also lacking. Fibronectin connecting segment-1 (FNCS1), an alternatively spliced fibronectin variant expressed by microvascular endothelial cells at sites of inflammation in vitro and in situ, is a counterligand for leukocyte α4 integrin (also known as CD49d) implicated in pathogenic leukocyte trafficking in multiple sclerosis and inflammatory bowel disease. We sought to det...
Source: Experimental Neurology - February 16, 2017 Category: Neurology Authors: Dong C, Greathouse KM, Beacham RL, Palladino SP, Scott Helton E, Ubogu EE Tags: Exp Neurol Source Type: research

IgG-degrading enzyme of Streptococcus pyogenes (IdeS) prevents disease progression and facilitates improvement in a rabbit model of Guillain-Barr é syndrome.
In this study, using a rabbit model of axonal GBS, acute motor axonal neuropathy (AMAN), we demonstrated that IdeS treatment significantly reduced the disruption of Nav channels as well as activated C3 deposition at the anterior spinal root nodes of Ranvier in AMAN rabbits. IdeS significantly promoted the clinical recovery of AMAN rabbits and there were significant lower frequencies of axonal degeneration in anterior spinal roots of AMAN rabbits with IdeS treatment compared to the saline controls. Our data support that IdeS treatment is a promising therapeutic strategy for GBS. PMID: 28214515 [PubMed - as supplied by ...
Source: Experimental Neurology - February 15, 2017 Category: Neurology Authors: Wang Y, Shi Q, Lv H, Hu M, Wang W, Wang Q, Qiao B, Zhang G, Lv Z, Kjellman C, Järnum S, Winstedt L, Zhang Y, Wen J, Hao Y, Yuki N Tags: Exp Neurol Source Type: research

Saturation of long-term potentiation in the dorsal cochlear nucleus and its pharmacological reversal in an experimental model of tinnitus.
Abstract Animal models have demonstrated that tinnitus is a pathology of dysfunctional excitability in the central auditory system, in particular in the dorsal cochlear nucleus (DCN) of the brainstem. We used a murine model and studied whether acoustic over-exposure leading to hearing loss and tinnitus, affects long-term potentiation (LTP) at DCN multisensory synapses. Whole cell and field potential recordings were used to study the effects on release probability and synaptic plasticity, respectively in brainstem slices. Shifts in hearing threshold were quantified by auditory brainstem recordings, and gap-induced ...
Source: Experimental Neurology - February 15, 2017 Category: Neurology Authors: Tagoe T, Deeping D, Hamann M Tags: Exp Neurol Source Type: research

Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats.
Abstract Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar p...
Source: Experimental Neurology - February 9, 2017 Category: Neurology Authors: Alam M, Garcia-Alias G, Jin B, Keyes J, Zhong H, Roy RR, Gerasimenko Y, Lu DC, Edgerton VR Tags: Exp Neurol Source Type: research

Progressive leukoencephalopathy impairs neurobehavioral development in sialin-deficient mice.
e R Abstract Slc17a5(-/-) mice represent an animal model for the infantile form of sialic acid storage disease (SASD). We analyzed genetic and histological time-course expression of myelin and oligodendrocyte (OL) lineage markers in different parts of the CNS, and related this to postnatal neurobehavioral development in these mice. Sialin-deficient mice display a distinct spatiotemporal pattern of sialic acid storage, CNS hypomyelination and leukoencephalopathy. Whereas few genes are differentially expressed in the perinatal stage (p0), microarray analysis revealed increased differential gene expression in later p...
Source: Experimental Neurology - February 9, 2017 Category: Neurology Authors: Stroobants S, Van Acker NG, Verheijen FW, Goris I, Daneels GF, Schot R, Verbeek E, Knaapen MW, De Bondt A, Göhlmann HW, Crauwels ML, Mancini GM, Andries LJ, Moechars DW, D'Hooge R Tags: Exp Neurol Source Type: research

Optimization of trophic support for neural stem cell grafts in sites of spinal cord injury.
Abstract Previously we utilized fibrin matrices and a cocktail of nine growth factors and a cell death inhibitor to promote survival and fill of neural stem cell (NSC) or neural progenitor cell (NPC) grafts to sites of spinal cord injury (SCI). In the current study, we examined whether the number of growth factors in a supportive matrix could be reduced to a more clinically practical number while retaining extensive NPC survival and fill of a spinal cord lesion site. NPCs derived from embryonic day 14 Fischer 344 rat spinal cords expressing green fluorescent protein (GFP) were embedded in fibrin matrices containin...
Source: Experimental Neurology - February 8, 2017 Category: Neurology Authors: Robinson J, Lu P Tags: Exp Neurol Source Type: research