Targeting the cytoskeleton with an FDA approved drug to promote recovery after spinal cord injury.
PMID: 29752944 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 9, 2018 Category: Neurology Authors: Vagnozzi AN, Silver J Tags: Exp Neurol Source Type: research

Oligodendrocyte-specific loss of Cdk5 disrupts the architecture of nodes of Ranvier as well as learning and memory.
Abstract Myelination of the central nervous system is important for normal motor and sensory neuronal function and recent studies also link it to efficient learning and memory. Cyclin-dependent kinase 5 (Cdk5) is required for normal oligodendrocyte development, myelination and myelin repair. Here we show that conditional deletion of Cdk5 by targeting with CNP (CNP;Cdk5 CKO) results in hypomyelination and disruption of the structural integrity of Nodes of Ranvier. In addition, CNP;Cdk5 CKO mice exhibited a severe impairment of learning and memory compared to controls that may reflect perturbed neuron-glial interact...
Source: Experimental Neurology - May 2, 2018 Category: Neurology Authors: Luo F, Zhang J, Burke K, Romito-DiGiacomo RR, Miller RH, Yang Y Tags: Exp Neurol Source Type: research

Ionic plasticity and pain: The loss of descending serotonergic fibers after spinal cord injury transforms how GABA affects pain.
Abstract Activation of pain (nociceptive) fibers can sensitize neural circuits within the spinal cord, inducing an increase in excitability (central sensitization) that can foster chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. In adult animals, the co-transporter KCC2 maintains a low intracellular concentration of the anion Cl-. As a result, when the GABA-A receptor is engaged, Cl- flows in the neuron which has a hyperpolarizing (inhibitory) effect. Spinal cord injury (SCI) can down-regulate KCC2 and reverse the flow of Cl-. Un...
Source: Experimental Neurology - May 2, 2018 Category: Neurology Authors: Huang YJ, Grau JW Tags: Exp Neurol Source Type: research

Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.
Abstract The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion. Here we examine the molecular mechanisms of stimulation-dependent CST axo...
Source: Experimental Neurology - May 2, 2018 Category: Neurology Authors: Zareen N, Dodson S, Armada K, Awad R, Sultana N, Hara E, Alexander H, Martin JH Tags: Exp Neurol Source Type: research

Neurosteroid allopregnanolone reduces ipsilateral visual cortex potentiation following unilateral optic nerve injury.
We examined visually evoked potentials (VEP) in the primary visual cortex ipsilateral and contralateral to the crushed nerve. We found that unilateral ONC induces enhancement of visual response on the side ipsilateral to the injury that is evoked by visual stimulation to the intact eye. This enhancement was associated with supranormal spatial frequency thresholds in the intact eye when tested using optomotor response. To probe whether injury-induced disinhibition caused the potentiation, we treated animals with the neurosteroid allopregnanolone, a potent agonist of the GABAA receptor, one hour after crush and on post-injur...
Source: Experimental Neurology - May 2, 2018 Category: Neurology Authors: Sergeeva EG, Espinosa-Garcia C, Atif F, Pardue MT, Stein DG Tags: Exp Neurol Source Type: research

Application of optogenetics in the study of pain modulation.
Abstract Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in the activity of nociceptive sensory afferents and dorsal horn cell populations contribute to the onset and maintenance of chronic pain. Through the application of advances in genetic techniques, there has been a surge in the success of efforts along this front. In particular, the past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents ...
Source: Experimental Neurology - May 2, 2018 Category: Neurology Authors: Xie YF, Wang J, Bonin RP Tags: Exp Neurol Source Type: research

TRPV4 inhibition prevents paclitaxel-induced neurotoxicity in preclinical models.
Abstract Paclitaxel is a cytotoxic drug which frequently causes sensory peripheral neuropathy in patients. Increasing evidence suggests that altered intracellular calcium (Ca2+) signals play an important role in the pathogenesis of this condition. In the present study, we examined the interplay between Ca2+ release channels in the endoplasmic reticulum (ER) and Ca2+ permeable channels in the plasma membrane in the context of paclitaxel mediated neurotoxicity. We observed that in small to medium size dorsal root ganglia neurons (DRGN) the inositol-trisphosphate receptor (InsP3R) type 1 was often concentrated in the...
Source: Experimental Neurology - April 28, 2018 Category: Neurology Authors: Boehmerle W, Huehnchen P, Lee SLL, Harms C, Endres M Tags: Exp Neurol Source Type: research

RhoA activation in axotomy-induced neuronal death.
Abstract After spinal cord injury (SCI) in mammals, severed axons fail to regenerate, due to both extrinsic inhibitory factors, e.g., the chondroitin sulfate proteoglycans (CSPGs) and myelin-associated growth inhibitors (MAIs), and a developmental loss of intrinsic growth capacity. The latter is suggested by findings in lamprey that the 18 pairs of individually identified reticulospinal neurons vary greatly in their ability to regenerate their axons through the same spinal cord environment. Moreover, those neurons that are poor regenerators undergo very delayed apoptosis, and express common molecular markers after...
Source: Experimental Neurology - April 28, 2018 Category: Neurology Authors: Zhang G, Hu J, Rodemer W, Li S, Selzer ME Tags: Exp Neurol Source Type: research

Epigenetic upregulation of CXCL12 expression contributes to the acquisition and maintenance of morphine-induced conditioned place preference.
Abstract Addiction and rewarding effect is a primary side effect of morphine, which is commonly used to relieve the acute or chronic pain. Several lines of evidence have suggested that inflammation response in the VTA contributes to morphine-induced reward (conditioned place preference, CPP), while the mechanism are poorly understood. The present study showed that repeated morphine conditioning persistently increased the expression of CXCL12 mRNA and protein in VTA. Furthermore, inhibition of CXCL12 prevented the acquisition and maintenance, but not the expression, of morphine-induced CPP in rodent. In addition, m...
Source: Experimental Neurology - April 28, 2018 Category: Neurology Authors: Liu H, Wei J, Liu M, Wu S, Ma C, Liu C, Huang K, Zhang X, Guo R, Zhang K, Xin W Tags: Exp Neurol Source Type: research

New HSF1 inducer as a therapeutic agent in a rodent model of Parkinson's disease.
Abstract Molecular chaperone HSP70 (HSPA1A) has therapeutic potential in conformational neurological diseases. Here we evaluate the neuroprotective function of the chaperone in a rat model of Parkinson's disease (PD). We show that the knock-down of HSP70 (HSPA1A) in dopaminergic neurons of the Substantia nigra causes an almost 2-fold increase in neuronal death and multiple motor disturbances in animals. Conversely, pharmacological activation of HSF1 transcription factor and enhanced expression of inducible HSP70 with the echinochrome derivative, U-133, reverses the process of neurodegeneration, as evidenced by а ...
Source: Experimental Neurology - April 25, 2018 Category: Neurology Authors: Ekimova IV, Plaksina DV, Pastukhov YF, Lapshina KV, Lazarev VF, Mikhaylova ER, Polonik SG, Pani B, Margulis BA, Guzhova IV, Nudler E Tags: Exp Neurol Source Type: research

The cytoskeleton in 'couch potato-ism': Insights from a murine model of impaired actin dynamics.
g G Abstract Evidence for a critical pathophysiological role of aberrant cytoskeletal dynamics is being uncovered in a growing number of neuropsychiatric syndromes. A sedentary lifestyle as well as overt psychopathology is prevalent in patients with the metabolic syndrome. Using mice deficient in gelsolin (Gsn-/-), a crucial actin-severing protein, we here investigated reduced actin turnover as a potential common driver of metabolic disturbances, sedentary behavior, and an anxious/depressive phenotype. Gelsolin deficiency resulted in reduced lifespan. As compared to wildtype controls, Gsn-/- mice (~ 9 weeks) fed a...
Source: Experimental Neurology - April 20, 2018 Category: Neurology Authors: Gertz K, Uhlemann R, Foryst-Ludwig A, Barrientos RM, Kappert K, Thöne-Reineke C, Djoufack P, Kirschbaum C, Fink KB, Heinz A, Kintscher U, Endres M, Kronenberg G Tags: Exp Neurol Source Type: research

The effect of myelotomy following low thoracic spinal cord compression injury in rats.
Abstract Myelotomy is a surgical procedure allowing removal of extravasated blood and necrotic tissue that is thought to attenuate secondary injury as well as promote recovery in experimental spinal cord injury (SCI) models and humans. Here we examined in rat whether myelotomy at 48 h after low-thoracic compressive SCI provided any benefit over a 12 week period. Compared to animals receiving SCI alone, myelotomy worsened BBB scores (p 
Source: Experimental Neurology - April 18, 2018 Category: Neurology Authors: Meyer C, Bendella H, Rink S, Gensch R, Seitz R, Stein G, Manthou M, Papamitsou T, Nakamura M, Bouillon B, Galea M, Batchelor P, Dunlop S, Angelov D Tags: Exp Neurol Source Type: research

Lysophosphatidic acid induces neuronal cell death via activation of asparagine endopeptidase in cerebral ischemia-reperfusion injury.
Abstract Lysophosphatidic acid (LPA), an extracellular signaling molecule, influences diverse biological events, including the pathophysiological process induced after ischemic brain injury. However, the molecular mechanisms mediating the pathological change after ischemic stroke remain elusive. Here we report that asparagine endopeptidase (AEP), a lysosomal cysteine proteinase, is regulated by LPA during stroke. AEP proteolytically cleaves tau and generates tauN368 fragments, triggering neuronal death. Inhibiting the generation of LPA reduces the expression of AEP and tauN368, and alleviates neuronal cell death. ...
Source: Experimental Neurology - April 16, 2018 Category: Neurology Authors: Wang C, Zhang J, Tang J, Li YY, Gu Y, Yu Y, Xiong J, Zhao X, Zhang Z, Li TT, Chen J, Wan Q, Zhang Z Tags: Exp Neurol Source Type: research

Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice.
Abstract Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time...
Source: Experimental Neurology - April 13, 2018 Category: Neurology Authors: Song J, Chu S, Cui Y, Qian Y, Li X, Xu F, Shao X, Ma Z, Xia T, Gu X Tags: Exp Neurol Source Type: research

Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2.
Abstract Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver dysfunction and severe neurological manifestations, resulting in early death. There is no effective therapy for NPC2 disease. Here, we evaluated the effectiveness of an adeno-associated virus (AAV), serotype rh.10 gene transfer vector expressing the mouse Npc2 gene (AAVrh.10-mNpc2-HA, HA tagged to facilitate analysis) to treat the disease in an Npc2-/- mouse model. A s...
Source: Experimental Neurology - April 12, 2018 Category: Neurology Authors: Markmann S, Reid J, Rosenberg JB, De BP, Kaminsky SM, Crystal RG, Sondhi D Tags: Exp Neurol Source Type: research

Glia maturation factor beta is required for reactive gliosis after traumatic brain injury in zebrafish.
Abstract Gliosis is a hallmark of neural pathology that occurs after most forms of central nervous system (CNS) injuries including traumatic brain injury (TBI). Identification of genes that control gliosis may provide novel treatment targets for patients with diverse CNS injuries. Glia maturation factor beta (GMFB) is crucial in brain development and stress response. In the present study, GMFB was found to be widely expressed in adult zebrafish telencephalon. A gmfb mutant zebrafish was created using CRISPR/cas9. In the uninjured zebrafish telencephalon, glial fibrillary acidic protein (GFAP) fibers in gmfb mutant...
Source: Experimental Neurology - April 12, 2018 Category: Neurology Authors: Yin G, Du M, Li R, Li K, Huang X, Duan D, Ai X, Yao F, Zhang L, Hu Z, Wu B Tags: Exp Neurol Source Type: research

Constraint-induced movement therapy improves efficacy of task-specific training after severe cortical stroke depending on the ipsilesional corticospinal projections.
Abstract Descending spinal pathways (corticospinal, rubrospinal, and reticulospinal) are believed to contribute to functional recovery resulting from rehabilitative training after stroke. However, the contribution of each pathway remains unclear. In the current study, we investigated rehabilitation-induced functional recovery and remodelling of the descending spinal pathways after severe cortical stroke in rats followed by 3 weeks of various rehabilitation [constraint-induced movement therapy (CIMT), skilled forelimb reaching, rotarod, and treadmill exercise]. Following photothrombotic stroke, 96% of corticospin...
Source: Experimental Neurology - April 10, 2018 Category: Neurology Authors: Okabe N, Himi N, Nakamura-Maruyama E, Hayashi N, Sakamoto I, Narita K, Hasegawa T, Miyamoto O Tags: Exp Neurol Source Type: research

Mid-cervical spinal cord contusion causes robust deficits in respiratory parameters and pattern variability.
Abstract Mid-cervical spinal cord contusion disrupts both the pathways and motoneurons vital to the activity of inspiratory muscles. The present study was designed to determine if a rat contusion model could result in a measurable deficit to both ventilatory and respiratory motor function under "normal" breathing conditions at acute to chronic stages post trauma. Through whole body plethysmography and electromyography we assessed respiratory output from three days to twelve weeks after a cervical level 3 (C3) contusion. Contused animals showed significant deficits in both tidal and minute volumes which w...
Source: Experimental Neurology - April 10, 2018 Category: Neurology Authors: Warren PM, Campanaro C, Jacono FJ, Alilain WJ Tags: Exp Neurol Source Type: research

Ketamine reduces deleterious consequences of spreading depolarizations.
Abstract Recent work has implicated spreading depolarization (SD) as a key contributor the progression of acute brain injuries, however development of interventions selectively targeting SDs has lagged behind. Initial clinical intervention efforts have focused on observations that relatively high doses of the sedative agent ketamine can completely suppress SD. However blocking propagation of SD could theoretically prevent beneficial effects of SD in surrounding brain regions. Selective targeting of deleterious consequences of SD (rather than abolition) could be a useful adjunct approach, and be achieved with lower...
Source: Experimental Neurology - April 10, 2018 Category: Neurology Authors: Reinhart KM, William Shuttleworth C Tags: Exp Neurol Source Type: research

Deletion of the insulin receptor in sensory neurons increases pancreatic insulin levels.
Abstract Insulin is known to have neurotrophic properties and loss of insulin support to sensory neurons may contribute to peripheral diabetic neuropathy (PDN). Here, genetically-modified mice were generated in which peripheral sensory neurons lacked the insulin receptor (SNIRKO mice) to determine whether disrupted sensory neuron insulin signaling plays a crucial role in the development of PDN and whether SNIRKO mice develop symptoms of PDN due to reduced insulin neurotrophic support. Our results revealed that SNIRKO mice were euglycemic and never displayed significant changes in a wide range of sensorimotor behav...
Source: Experimental Neurology - April 9, 2018 Category: Neurology Authors: Grote CW, Wilson NM, Katz NK, Guilford BL, Ryals JM, Novikova L, Stehno-Bittel L, Wright DE Tags: Exp Neurol Source Type: research

Estrogen-related receptor alpha is involved in Alzheimer's disease-like pathology.
Abstract Estrogen-related receptor alpha (ERRα) is a transcriptional factor associated with mitochondrial biogenesis and energy metabolism. However, little is known about the role of ERRα in Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, ERRα protein and mRNA were decreased in a region- and age-dependent manner. In HEK293 cells that stably express human full-length β-amyloid precursor protein (APP), overexpression of ERRα inhibited the amyloidogenic processing of APP and consequently reduced Aβ1-40/1-42 level. ERRα overexpression also ...
Source: Experimental Neurology - April 8, 2018 Category: Neurology Authors: Tang Y, Min Z, Xiang XJ, Liu L, Ma YL, Zhu BL, Song L, Tang J, Deng XJ, Yan Z, Chen GJ Tags: Exp Neurol Source Type: research

Brain pericyte activation occurs early in Huntington's disease.
l G Abstract Microvascular changes have recently been described for several neurodegenerative disorders, including Huntington's disease (HD). HD is characterized by a progressive neuronal cell loss due to a mutation in the Huntingtin (HTT) gene. However, the temporal and spatial microvascular alterations in HD remain unclear. Also, knowledge on the implication of pericytes in HD pathology is still sparse and existing findings are contradictory. Here we examine alterations in brain pericytes in the R6/2 mouse model of HD and in human post mortem HD brain sections. To specifically track activated pericytes, we cross...
Source: Experimental Neurology - April 6, 2018 Category: Neurology Authors: Padel T, Roth M, Gaceb A, Li JY, Björkqvist M, Paul G Tags: Exp Neurol Source Type: research

Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.
Abstract The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration ...
Source: Experimental Neurology - March 30, 2018 Category: Neurology Authors: Kamizato K, Marsala S, Navarro M, Kakinohana M, Platoshyn O, Yoshizumi T, Lukacova N, Wancewicz E, Powers B, Mazur C, Marsala M Tags: Exp Neurol Source Type: research

Molecular pathology of Multiple Sclerosis lesions reveals a heterogeneous expression pattern of genes involved in oligodendrogliogenesis.
Abstract Little is known about the decisive molecular factors that regulate lesion remyelination in Multiple Sclerosis. To identify such factors, we performed a differential gene expression analysis of normal appearing white matter (NAWM), active, remyelinating, and inactive demyelinated lesions. As expected, many genes involved in inflammatory processes were detected to be differentially regulated between these tissue types. Among them, we found an increased expression of members of the STAT6 pathway such as STAT6, IL4 and IL4R in active, remyelinated and inactive demyelinated lesions. This suggests that a protec...
Source: Experimental Neurology - March 26, 2018 Category: Neurology Authors: Zeis T, Howell OW, Reynolds R, Schaeren-Wiemers N Tags: Exp Neurol Source Type: research

Spontaneous respiratory plasticity following unilateral high cervical spinal cord injury in behaving rats.
Abstract Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord injury (SCI) for studying respiratory dysfunction and plasticity. However, most previous studies were performed under anesthesia, which significantly alters respiratory network. Therefore, the goal of this work was to assess spontaneous diaphragm recovery post-C2Hx in awake, freely behaving animals. Adult rats were chronically implanted with diaphragm EMG electrodes and recorded during 8 weeks post-C2Hx. Our results reveal that ipsilateral diaphragm activity partially recovers within days post-injury and reaches pre-injury ampli...
Source: Experimental Neurology - March 26, 2018 Category: Neurology Authors: Bezdudnaya T, Hormigo KM, Marchenko V, Lane MA Tags: Exp Neurol Source Type: research

Impaired social behaviors and minimized oxytocin signaling of the adult mice deficient in the N-methyl-d-aspartate receptor GluN3A subunit.
In this study, we sought to evaluate altered social activities in adult GluN3A knockout (KO) mice. GluN3A KO mice spent less time in reciprocal social interaction in the social interaction test compared to wild-type (WT) mice. A social approach test using a three-chamber system confirmed that mice lacking GluN3A had lower sociability and did not exhibit a preference for social novelty. GluN3A KO mice displayed abnormal food preference in the social transmission of food preference task and low social interaction activity in the five-trial social memory test, but without social memory deficits. Using a home cage monitoring s...
Source: Experimental Neurology - March 16, 2018 Category: Neurology Authors: Lee JH, Zhang JY, Wei ZZ, Yu SP Tags: Exp Neurol Source Type: research

Transcriptional networks of progressive diabetic peripheral neuropathy in the db/db mouse model of type 2 diabetes: An inflammatory story.
Abstract Diabetic peripheral neuropathy is the most common complication of diabetes and a source of considerable morbidity. Numerous molecular pathways are linked to neuropathic progression, but it is unclear whether these pathways are altered throughout the course of disease. Moreover, the methods by which these molecular pathways are analyzed can produce significantly different results; as such it is often unclear whether previously published pathways are viable targets for novel therapeutic approaches. In the current study we examine changes in gene expression patterns in the sciatic nerve (SCN) and dorsal root...
Source: Experimental Neurology - March 14, 2018 Category: Neurology Authors: Hinder LM, Murdock BJ, Park M, Bender DE, O'Brien PD, Rumora AE, Hur J, Feldman EL Tags: Exp Neurol Source Type: research

Persistent nature of alterations in cognition and neuronal circuit excitability after exposure to simulated cosmic radiation in mice.
Abstract Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars. Here we show that rodents exposed to the second most prevalent radiation type in sp...
Source: Experimental Neurology - March 11, 2018 Category: Neurology Authors: Parihar VK, Maroso M, Syage A, Allen BD, Angulo MC, Soltesz I, Limoli CL Tags: Exp Neurol Source Type: research

Cell based therapy enhances activation of ventral premotor cortex to improve recovery following primary motor cortex injury.
Abstract Stroke results in enduring damage to the brain which is accompanied by innate neurorestorative processes, such as reorganization of surviving circuits. Nevertheless, patients are often left with permanent residual impairments. Cell based therapy is an emerging therapeutic that may function to enhance the innate neurorestorative capacity of the brain. We previously evaluated human umbilical tissue-derived cells (hUTC) in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Injection of hUTC 24 h after injury resulted in significantly enhanced recovery of fine m...
Source: Experimental Neurology - March 11, 2018 Category: Neurology Authors: Orczykowski ME, Arndt KR, Palitz LE, Kramer BC, Pessina MA, Oblak AL, Finklestein SP, Mortazavi F, Rosene DL, Moore TL Tags: Exp Neurol Source Type: research

Mapping and neuromodulation of lower urinary tract function using spinal cord stimulation in female rats.
Abstract Spinal cord epidural stimulation (SCS) represents a form of neuromodulation for the management of spasticity and pain. This technology has recently emerged as a new approach for potentially augmenting locomotion and voiding function in humans and rodents after spinal cord injury. However, the effect of SCS on micturition has not been studied extensively. Here, SCS was first applied as a direct stimulus onto individual segmental levels of the lumbar spinal cord in rats to map evoked external urethral sphincter (EUS) electromyography activity and SCS-induced voiding contractions. SCS of L2-3 inhibited EUS t...
Source: Experimental Neurology - March 9, 2018 Category: Neurology Authors: Chang HH, Yeh JC, Ichiyama RM, Rodriguez LV, Havton LA Tags: Exp Neurol Source Type: research

Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease.
We report here that the neurotoxin 6-hydroxydopamine in rat lead to a rapid up-regulation of Nr4a1 in the substantia nigra. Genetic disruption of Nr4a1 in rat reduced neurotoxin-induced dopamine cell loss and l-Dopa-induced dyskinesia, whereas virally-driven striatal overexpression of Nr4a1 enhanced or partially restored involuntary movements induced by chronic l-Dopa in wild type and Nr4a1-deficient rats, respectively. Collectively, these results suggest that Nr4a1 is involved in dopamine cell loss and l-dopa-induced dyskinesia in experimental PD. PMID: 29530712 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 9, 2018 Category: Neurology Authors: Rouillard C, Baillargeon J, Paquet B, St-Hilaire M, Maheux J, Lévesque C, Darlix N, Majeur S, Lévesque D Tags: Exp Neurol Source Type: research

DREADDed microglia in pain: Implications for spinal inflammatory signaling in male rats.
Abstract The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq- and Gi-coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which ...
Source: Experimental Neurology - March 9, 2018 Category: Neurology Authors: Grace PM, Wang X, Strand KA, Baratta MV, Zhang Y, Galer EL, Yin H, Maier SF, Watkins LR Tags: Exp Neurol Source Type: research

Serotonin receptor and dendritic plasticity in the spinal cord following chronic serotonergic pharmacotherapy combined with exercise following complete SCI in the adult rat.
Abstract Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy...
Source: Experimental Neurology - March 8, 2018 Category: Neurology Authors: Ganzer PD, Beringer CR, Shumsky JS, Nwaobasi C, Moxon KA Tags: Exp Neurol Source Type: research

Synaptic loss and firing alterations in Axotomized Motoneurons are restored by vascular endothelial growth factor (VEGF) and VEGF-B.
We examined the trophic role of VEGF on axotomized motoneurons with recordings in alert animals using the oculomotor system as the experimental model, complemented with a synaptic study at the confocal microscopy level. Axotomy leads to drastic alterations in the discharge characteristics of abducens motoneurons, as well as to a substantial loss of their synaptic inputs. Retrograde delivery of VEGF completely restored the discharge activity and synaptically-driven signals in injured motoneurons, as demonstrated by correlating motoneuronal firing rate with motor performance. Moreover, VEGF-treated motoneurons recovered a no...
Source: Experimental Neurology - March 6, 2018 Category: Neurology Authors: Calvo PM, de la Cruz RR, Pastor AM Tags: Exp Neurol Source Type: research

C9orf72 is essential for neurodevelopment and motility mediated by cyclin G1.
Abstract Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the function of C9orf72 in neural development and the pathogenic mechanism underlying neurodegeneration are unknown. We found that disrupting C9orf72 expression by using C9orf72 constructs that lack the complete DENN domain result in reduced GTPase activity in zebrafish embryos, demonstrating the indispensability of the complete DENN domain. This effect was phenocopied by knocking down endogenous C9orf72 expression by using...
Source: Experimental Neurology - March 6, 2018 Category: Neurology Authors: Yeh TH, Liu HF, Li YW, Lu CS, Shih HY, Chiu CC, Lin SJ, Huang YC, Cheng YC Tags: Exp Neurol Source Type: research

Subacute intranasal administration of tissue plasminogen activator improves stroke recovery by inducing axonal remodeling in mice.
Abstract In addition to thrombolysis, tissue plasminogen activator (tPA) can evoke neurorestorative processes. We therefore investigated the therapeutic effect of subacute intranasal administration of tPA post stroke on neurological recovery and on corticospinal innervation in mice. A transgenic mouse line, in which the pyramidal neurons and corticospinal tract (CST) axons are specifically labeled by yellow fluorescent protein (YFP) was employed. Adult CST-YFP mice were subjected to right unilateral middle cerebral artery occlusion (MCAo), and were randomly divided into groups treated with saline or tPA intranasal...
Source: Experimental Neurology - March 5, 2018 Category: Neurology Authors: Chen N, Chopp M, Xiong Y, Qian JY, Lu M, Zhou D, He L, Liu Z Tags: Exp Neurol Source Type: research

RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats.
Abstract Receptor for activated protein kinase C 1 (RACK1) is a multifaceted scaffolding protein known to be involved in the regulation of signaling events required for neuronal protection. In the present study, we investigated the role of RACK1 in secondary brain injury in a rat traumatic brain injury (TBI) model. A weight-drop TBI model was established in Sprague Dawley rats, and RACK1 in vivo knockdown and overexpression were performed 24 h before TBI insult. The IRE1 inhibitor 3,5-dibromosalicylaldehyde (DBSA) was administered by intracerebroventricular injection 1 h after TBI insult. Real-time PCR, Wester...
Source: Experimental Neurology - March 5, 2018 Category: Neurology Authors: Ni H, Rui Q, Xu Y, Zhu J, Gao F, Dang B, Li D, Gao R, Chen G Tags: Exp Neurol Source Type: research

Interactions between the Immune and Nervous systems in Nervous System Development, Diseases and Repair Processes.
Authors: PMID: 29496111 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - March 1, 2018 Category: Neurology Tags: Exp Neurol Source Type: research

Endophilin A1 mediates seizure activity via regulation of AMPARs in a PTZ-kindled epileptic mouse model.
This study found that the expression of endophilin A1 was significantly up-regulated in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of the PTZ-kindled epileptic mouse model. Behavioral analyses indicated that knockdown of endophilin A1 in the mouse hippocampus increased the latency of the first seizure and reduced the frequency and duration of seizure activity. Whole-cell patch-clamp recordings of pyramidal neurons in the hippocampal CA3 area indicated that knockdown of endophilin A1 in the mouse hippocampus resulted in a reduced frequency of action potentials and decreased am...
Source: Experimental Neurology - February 23, 2018 Category: Neurology Authors: Yu X, Xu T, Ou S, Yuan J, Deng J, Li R, Yang J, Liu X, Li Q, Chen Y Tags: Exp Neurol Source Type: research

Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation.
Abstract The Notch1 signaling pathway is considered as one of important regulators of angiogenesis during development, but its role in cerebral ischemia-induced angiogenesis is less well understood. Here, we used human and rodent brains to explore whether Notch1 signaling was involved in the angiogenesis after focal cerebral ischemia. Using immunohistochemistry on surgically resected ischemic stroke brain tissue, we found that the area, volume, and length of the blood vessels in the peri-infarct regions were significantly increased after ischemic stroke in humans, compared with non-ischemic stroke specimens. In ad...
Source: Experimental Neurology - February 23, 2018 Category: Neurology Authors: Ren C, Yao Y, Han R, Huang Q, Li H, Wang B, Li S, Li M, Mao Y, Mao X, Xie L, Zhou L, Hu J, Ji X, Jin K Tags: Exp Neurol Source Type: research

sAPP β and sAPPα increase structural complexity and E/I input ratio in primary hippocampal neurons and alter Ca2+ homeostasis and CREB1-signaling.
sAPPβ and sAPPα increase structural complexity and E/I input ratio in primary hippocampal neurons and alter Ca2+ homeostasis and CREB1-signaling. Exp Neurol. 2018 Feb 18;: Authors: Hesse R, von Einem B, Wagner F, Bott P, Schwanzar D, Jackson RJ, Föhr KJ, Lausser L, Kroker KS, Proepper C, Walther P, Kestler HA, Spires-Jones TL, Boeckers T, Rosenbrock H, von Arnim CAF Abstract One major pathophysiological hallmark of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). In the amyloidogenic pathway, cleavage of the amyloid precursor protein (APP) is shifted tow...
Source: Experimental Neurology - February 18, 2018 Category: Neurology Authors: Hesse R, von Einem B, Wagner F, Bott P, Schwanzar D, Jackson RJ, Föhr KJ, Lausser L, Kroker KS, Proepper C, Walther P, Kestler HA, Spires-Jones TL, Boeckers T, Rosenbrock H, von Arnim CAF Tags: Exp Neurol Source Type: research

Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway.
Abstract Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating e...
Source: Experimental Neurology - February 16, 2018 Category: Neurology Authors: Ruggiero RN, Rossignoli MT, Lopes-Aguiar C, Leite JP, Bueno-Junior LS, Romcy-Pereira RN Tags: Exp Neurol Source Type: research

Modest enhancement of sensory axon regeneration in the sciatic nerve with conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult mice.
Abstract Axons within the peripheral nervous system are capable of regeneration, but full functional recovery is rare. Recent work has shown that conditional deletion of two key signaling inhibitors of the PI3K and Jak/Stat pathways-phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3), respectively-promotes regeneration of normally non-regenerative central nervous system axons. Moreover, in studies of optic nerve regeneration, co-deletion of both PTEN and SOCS3 has an even greater effect. Here, we test the hypotheses (1) that PTEN deletion enhances axon regeneration following sciati...
Source: Experimental Neurology - February 16, 2018 Category: Neurology Authors: Gallaher ZR, Steward O Tags: Exp Neurol Source Type: research

Cell-type specific expression of constitutively-active Rheb promotes regeneration of bulbospinal respiratory axons following cervical SCI.
Abstract Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Urban MW, Ghosh B, Strojny LR, Block CG, Blazejewski SM, Wright MC, Smith GM, Lepore AC Tags: Exp Neurol Source Type: research

Amelioration of progressive autoimmune encephalomyelitis by epigenetic regulation involves selective repression of mature neutrophils during the preclinical phase.
Abstract We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II+) CD11b+Ly-6G+ neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase,...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Jayaraman A, Sharma M, Prabhakar B, Holterman M, Jayaraman S Tags: Exp Neurol Source Type: research

Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.
Abstract Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if th...
Source: Experimental Neurology - February 14, 2018 Category: Neurology Authors: Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Alboghobeish S, Amirgholami N, Houshmand G, Cauli O Tags: Exp Neurol Source Type: research

Activation of liver X receptor β-enhancing neurogenesis ameliorates cognitive impairment induced by chronic cerebral hypoperfusion.
This study correlates a deficit of LXRβ in cognitive dysfunction in CCH with impaired neurogenesis in hippocampus, and LXRs may serve as a potential therapeutic target for chronic cerebral ischemia. PMID: 29447944 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 12, 2018 Category: Neurology Authors: Sun T, Li YJ, Tian QQ, Wu Q, Feng D, Xue Z, Guo YY, Yang L, Zhang K, Zhao MG, Wu YM Tags: Exp Neurol Source Type: research

Phos-tau peptide immunization of amyloid-tg-mice reduced non-mutant phos-tau pathology, improved cognition and reduced amyloid plaques.
Abstract Tau-immumotherapy has shown promising results in tangle/tauopathy-tg animal models. Here we immunized amyloid-mice (APPSwe/PSEN1dE9-tg, presenting amyloid-plaques, not neurofibrillary-tangles) with phos-tau peptides, previously shown by us to have high efficacy in mutant-tau tauopathy-mice. These amyloid-mice allowed us to test the effect of the vaccine in a model of familial AD patients with mutant amyloid plaque pathology, where tau pathology - once develops - is of non-mutant tau. Fourteen-month-old amyloid-mice were immunized with phos-tau peptides or vehicle. Eight weeks later, amelioration of cognit...
Source: Experimental Neurology - February 9, 2018 Category: Neurology Authors: Benhamron S, Rozenstein-Tsalkovich L, Nitzan K, Abramsky O, Rosenmann H Tags: Exp Neurol Source Type: research

Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.
vy OA Abstract Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes e...
Source: Experimental Neurology - February 9, 2018 Category: Neurology Authors: Sun X, Aimé P, Dai D, Ramalingam N, Crary JF, Burke RE, Greene LA, Levy OA Tags: Exp Neurol Source Type: research

Nigrostriatal proteasome inhibition impairs dopamine neurotransmission and motor function in minipigs.
In conclusion, direct injection of lactacystin into the MFB of minipigs provides a model of PD with reduced dopamine neurotransmission, TH-positive neuron reduction, microglial activation and behavioural deficits. This large animal model could be useful in studies of symptomatic and neuroprotective therapies with translatability to human PD. PMID: 29428213 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: Lillethorup TP, Glud AN, Alstrup AKO, Mikkelsen TW, Nielsen EH, Zaer H, Doudet DJ, Brooks DJ, Sørensen JCH, Orlowski D, Landau AM Tags: Exp Neurol Source Type: research