Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid.
Abstract Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice wit...
Source: Experimental Neurology - December 1, 2014 Category: Neurology Authors: Iyengar SS, LaFrancois JJ, Friedman D, Drew LJ, Denny CA, Burghardt NS, Wu MV, Hsieh J, Hen R, Scharfman HE Tags: Exp Neurol Source Type: research

Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia.
Abstract MiR-181 has deleterious effects on stroke outcome, and reducing miR-181a levels prior to middle cerebral artery occlusion (MCAO) was shown previously to be protective. Here we tested the effect of post-ischemic treatment with miR-181a antagomir by intracerebroventricular and intravenous routes of administration on infarct size, neurological outcome, inflammatory response and long term behavioral outcome. Post-treatment with miR-181a antagomir significantly reduced infarction size, improved neurological deficits and reduced NF-κB activation, numbers of infiltrating leukocytes and levels of Ibal. Targ...
Source: Experimental Neurology - November 26, 2014 Category: Neurology Authors: Xu LJ, Ouyang YB, Xiong X, Stary CM, Giffard RG Tags: Exp Neurol Source Type: research

Nrf2-ARE Activator Carnosic Acid Decreases Mitochondrial Dysfunction, Oxidative Damage and Neuronal Cytoskeletal Degradation Following Traumatic Brain Injury in Mice.
This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. PMID: 25432068 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - November 25, 2014 Category: Neurology Authors: Miller DM, Singh IN, Wang JA, Hall ED Tags: Exp Neurol Source Type: research

Neuroepigenetics: Introduction to the special issue on epigenetics in neurodevelopment and neurological diseases.
PMID: 25432069 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - November 25, 2014 Category: Neurology Authors: Ming GL Tags: Exp Neurol Source Type: research

Application of neurophysiological biomarkers for Huntington's disease: Evaluating a phosphodiesterase 9A inhibitor.
e;s M Abstract Several neurophysiological abnormalities have been described in Huntington's disease, including auditory gating deficit, which are considered to reflect impaired brain information-processing. Since transgenic animal models of Huntington's disease capture basic neuropathology of the disorder, auditory gating was studied in BACHD (line5) transgenic rats and Q175 transgenic mice, together with local field gamma power in the hippocampus and primary auditory cortex. Using clinically equivalent acoustic-stimulation paradigms, impaired auditory gating was detected in transgenic BACHD rats under anesthesia ...
Source: Experimental Neurology - October 11, 2014 Category: Neurology Authors: Nagy D, Tingley FD, Stoiljkovic M, Hajós M Tags: Exp Neurol Source Type: research

The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis.
s E Abstract Vasoactive intestinal peptide (VIP) has potent immune modulatory actions that may influence the course of neurodegenerative disorders associated with chronic inflammation. Here, we show the therapeutic benefits of a modified peptide agonist stearyl-norleucine-VIP (SNV) in a transgenic rat model of amyotrophic lateral sclerosis (mutated superoxide dismutase 1, hSOD1(G93A)). When administered by systemic every-other-day intraperitoneal injections during a period of 80days before disease, SNV delayed the onset of motor dysfunction by no less than three weeks, while survival was extended by nearly two mon...
Source: Experimental Neurology - October 10, 2014 Category: Neurology Authors: Goursaud S, Schäfer S, Dumont AO, Vergouts M, Gallo A, Desmet N, Deumens R, Hermans E Tags: Exp Neurol Source Type: research

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease.
Abstract The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess...
Source: Experimental Neurology - October 5, 2014 Category: Neurology Authors: Bradbury AM, Gray-Edwards HL, Shirley JL, McCurdy VJ, Colaco AN, Randle AN, Christopherson PW, Bird AC, Johnson AK, Wilson DU, Hudson JA, De Pompa NL, Sorjonen DC, Brunson BL, Jeyakumar M, Platt FM, Baker HJ, Cox NR, Sena-Esteves M, Martin DR Tags: Exp Neurol Source Type: research

Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP(+) toxicity.
Abstract Exercise induces oxidative stress, which may activate adaptive antioxidant responses. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the defense of oxidative stress by regulating the expression of antioxidant enzymes, gamma-glutamylcysteine ligase (γGCL) and heme oxygenase-1 (HO-1). We investigated whether treadmill exercise protects dopaminergic neurons by regulating the Nrf2 antioxidant system in a 1-methyl-4-phenylpyridine (MPP(+))-induced parkinsonian rat model. We found that MPP(+) induced early decreases in total glutathione level and Nrf2/γGCLC (catalytic ...
Source: Experimental Neurology - October 5, 2014 Category: Neurology Authors: Tsou YH, Shih CT, Ching CH, Huang JY, Jen CJ, Yu L, Kuo YM, Wu FS, Chuang JI Tags: Exp Neurol Source Type: research

Early life seizures: Evidence for chronic deficits linked to autism and intellectual disability across species and models.
Abstract Recent work in Exp Neurol by Lugo et al. (2014b) demonstrated chronic alterations in sociability, learning and memory following multiple early life seizures (ELSs) in a mouse model. This work adds to the growing body of evidence supporting the detrimental nature of ELSs on the developing brain to contribute to aspects of an autistic phenotype with intellectual disability. Review of the face validity of behavioral testing and the construct validity of the models used informs the predictive ability and thus the utility of these models to translate underlying molecular and cellular mechanisms into future hum...
Source: Experimental Neurology - October 2, 2014 Category: Neurology Authors: Bernard PB, Benke TA Tags: Exp Neurol Source Type: research

NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke.
NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke. Exp Neurol. 2014 Sep 30; Authors: Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, Zhao LR Abstract Chronic stroke is the phase of brain recovery and repair generally beginning 3 months after stroke onset. No pharmaceutical approach is currently available to enhance brain repair in the chronic stroke. We have previously determined the therapeutic effects of stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) alone or in combination (SCF+G-CSF) in an animal mo...
Source: Experimental Neurology - September 30, 2014 Category: Neurology Authors: Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, Zhao LR Tags: Exp Neurol Source Type: research

Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats.
Abstract Previously, we showed that activation of the spinal CXCL9, 10/CXCR3 pathway mediated bone cancer pain (BCP) in rats. However, the cellular mechanism involved is poorly understood. Here, we found that the activated CXCR3 was co-localized with either neurons, microglia, and astrocytes in the spinal cord, or non-peptidergic-, peptidergic-, and A-type neurons in the dorsal root ganglion. The inoculation of Walker-256 mammary gland carcinoma cells into the rat's tibia induced a time-dependent phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2) in the spinal cord, and CXCR3 was necessary f...
Source: Experimental Neurology - September 30, 2014 Category: Neurology Authors: Guan XH, Fu QC, Shi D, Bu HL, Song ZP, Xiong BR, Shu B, Xiang HB, Xu B, Manyande A, Cao F, Tian YK Tags: Exp Neurol Source Type: research

Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells via Wnt / GSK3β signaling.
Electric Signals Regulate Directional Migration of Ventral Midbrain Derived Dopaminergic Neural Progenitor Cells via Wnt / GSK3β signaling. Exp Neurol. 2014 Sep 26; Authors: Liu J, Zhu B, Zhang G, Wang J, Tian W, Ju G, Wei X, Song B Abstract Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulat...
Source: Experimental Neurology - September 26, 2014 Category: Neurology Authors: Liu J, Zhu B, Zhang G, Wang J, Tian W, Ju G, Wei X, Song B Tags: Exp Neurol Source Type: research

Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism.
In this study, we investigated the neuroprotective mechanism and therapeutic effect of ALDH2 in rotenone models for parkinsonism. Overexpression of wild-type ALDH2 gene, but not the enzymatically deficient mutant ALDH2*2 (E504K), reduced rotenone-induced cell death. Application of a potent activator of ALDH2, Alda-1, was effective in protecting against rotenone-induced apoptotic cell death in both SH-SY5Y cells and primary cultured substantia nigra (SN) dopaminergic neurons. In addition, intraperitoneal administration of Alda-1 significantly reduced rotenone- or MPTP-induced death of SN tyrosine hydroxylase (TH)-positive d...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CS Tags: Exp Neurol Source Type: research

Epigenetic Mechanisms of Neuroplasciticy and the Implications for Stroke Recovery.
Abstract Ischemic stroke is a devastating brain injury and an important cause of neurologic disability worldwide and across the lifespan. Despite the physical, social, and economic burdens of this disease there is only a single approved medicine for the treatment of acute stroke, and its use is unfortunately limited to the small fraction of patients presenting within the narrow therapeutic window. Following stroke, there is a period of plasticity involving cell genesis, axon growth, and synaptic modulation that is essential to spontaneous recovery. Treatments focusing on neuroprotection and enhancing recovery have...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Felling RJ, Song H Tags: Exp Neurol Source Type: research

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible.
Abstract Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurolo...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Zia MT, Vinukonda G, Vose L, Bhimavarapu BB, Iacobas S, Pandey NK, Beall AM, Dohare P, LaGamma EF, Iacobas DA, Ballabh P Tags: Exp Neurol Source Type: research

Behavioral effects and mechanisms of migraine pathogenesis following estradiol exposure in a multibehavioral model of migraine in rat.
Abstract Migraine is one of the most common neurological disorders, leading to more than 1% of total disability reported and over 68 million visits to emergency rooms or physician's offices each year in the United States. Three times as many women as men have migraine, and while the mechanism behind this is not well understood, 17β-estradiol (estradiol) has been implicated to play a role. Studies have demonstrated that exposure to estrogen can lead to activation of inflammatory pathways, changes in sodium gated channel activity, as well as enhanced vasodilation and allodynia. Estradiol receptors are found in ...
Source: Experimental Neurology - September 25, 2014 Category: Neurology Authors: Vermeer LM, Gregory E, Winter MK, McCarson KE, Berman NE Tags: Exp Neurol Source Type: research

The α7 nicotinic receptor agonist ABT-107 protects against nigrostriatal damage in rats with unilateral 6-hydroxydopamine lesions.
The objective of this study was twofold: first, to test the protective potential of ABT-107, an agonist with high selectivity for α7 nAChRs; and second, to investigate its cellular mechanism of action. Rats were implanted with minipumps containing ABT-107 (0.25mg/kg/d). In addition, we tested the effect of nicotine (1mg/kg/d) as a positive control, and also DMXB (2mg/kg/d) which acts primarily with α7 but also α4β2* nAChRs. Two wk after minipump placement, the rats were lesioned by unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Lesioning alone decreased cont...
Source: Experimental Neurology - September 24, 2014 Category: Neurology Authors: Bordia T, McGregor M, Papke RL, Decker MW, Michael McIntosh J, Quik M Tags: Exp Neurol Source Type: research

Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves.
Abstract The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, ...
Source: Experimental Neurology - September 24, 2014 Category: Neurology Authors: Joshi AR, Bobylev I, Zhang G, Sheikh K, Lehmann HC Tags: Exp Neurol Source Type: research

Combination of Methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system.
In conclusion, both HIV-1/gp120 and METH caused lasting behavioral impairment in association with neuropathology and altered gene expression. However, combined METH exposure and HIV-1/gp120 expression resulted in the most pronounced, long lasting pre- and post-synaptic alterations coinciding with impaired learning and memory. PMID: 25246228 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 19, 2014 Category: Neurology Authors: Hoefer MM, Sanchez AB, Maung R, de Rozieres CM, Catalan IC, Dowling CC, Thaney VE, Piña-Crespo J, Zhang D, Roberts AJ, Kaul M Tags: Exp Neurol Source Type: research

The influence of the HPG axis on stress response and depressive-like behaviour in a transgenic mouse model of Huntington's disease.
Abstract Huntington's disease (HD) is an autosomal dominant, neurodegenerative disease caused by a CAG tandem repeat mutation encoding a polyglutamine tract expansion in the huntingtin protein. Depression is among the most common affective symptoms in HD but the pathophysiology is unclear. We have previously discovered sexually dimorphic depressive-like behaviours in the R6/1 transgenic mouse model of HD at a pre-motor symptomatic age. Interestingly, only female R6/1 mice display this phenotype. Sexual dimorphism has not been explored in the human HD population despite the well-established knowledge that the clini...
Source: Experimental Neurology - September 19, 2014 Category: Neurology Authors: Du X, Pang TY, Mo C, Renoir T, Wright D, Hannan AJ Tags: Exp Neurol Source Type: research

Delivery of therapeutic protein for prevention of neurodegenerative changes: Comparison of different CSF-delivery methods.
Abstract Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute studies in mucopolysaccharidosis (MPS) type II mice revealed that intrathecally-delivered enzyme (into thoraco-lumbar CSF) accesses the brain, the impact of longer-term treatment of affected subjects via this route is unknown. This approach is presently being utilized to treat children with M...
Source: Experimental Neurology - September 19, 2014 Category: Neurology Authors: Marshall NR, Hassiotis S, King B, Rozaklis T, Trim PJ, Duplock SK, Winner LK, Beard H, Snel MF, Jolly RD, Hopwood JJ, Hemsley KM Tags: Exp Neurol Source Type: research

Over-expression of P2X7 receptors in spinal glial cells contributes to the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR) in rats.
Abstract Many patients suffer from chronic postsurgical pain (CPSP) following surgery, and the underlying mechanisms are poorly understood. In the present work, with use of skin/muscle incision and retraction (SMIR) model, the role of P2X7 receptors (P2X7Rs) in spinal glial cells in the development of CPSP was evaluated. Consistence with previous reports, we found that SMIR decreased the ipsilateral 50% paw withdrawal threshold (PWT), lasting for at least 2weeks. No injury was done to L3 dorsal root ganglia (DRG) neurons and no axonal or Schwann cell damage at the retraction site in the saphenous nerve was observe...
Source: Experimental Neurology - September 18, 2014 Category: Neurology Authors: Ying YL, Wei XH, Xu XB, She SZ, Zhou LJ, Lv J, Li D, Zheng B, Liu XG Tags: Exp Neurol Source Type: research

Improving peripheral nerve regeneration: From molecular mechanisms to potential therapeutic targets.
Abstract Peripheral nerve injury is common especially among young individuals. Although injured neurons have the ability to regenerate, the rate is slow and functional outcomes are often poor. Several potential therapeutic agents have shown considerable promise for improving the survival and regenerative capacity of injured neurons. These agents are reviewed within the context of their molecular mechanisms. The PI3K/Akt and Ras/ERK signaling cascades play a key role in neuronal survival. A number of agents that target these pathways, including erythropoietin, tacrolimus, acetyl-l-carnitine, n-acetylcysteine and ge...
Source: Experimental Neurology - September 15, 2014 Category: Neurology Authors: Chan KM, Gordon T, Zochodne DW, Power HA Tags: Exp Neurol Source Type: research

Increased neurotrophic factor levels in ventral mesencephalic cultures do not explain the protective effect of osteopontin and the synthetic 15-mer RGD domain against MPP+toxicity.
Abstract The synthetic 15-mer arginine-glycine-aspartic acid (RGD) domain of osteopontin (OPN) is protective in vitro and in vivo against dopaminergic cell death and this protective effect may be mediated through an interaction with integrin receptors to regulate neurotrophic factor levels (Iczkiewicz, 2010). We now examine this concept in rat primary ventral mesencephalic (VM) cultures. 1-methyl-4-phenylpyridinium (MPP+) exposure reduced tyrosine hydroxylase (TH)-positive cell number and activated glial cells as shown by increased glial fibrillary acidic protein (GFAP), oxycocin-42 (OX-42) and Ectodermal dysplasi...
Source: Experimental Neurology - September 11, 2014 Category: Neurology Authors: Broom L, Jenner P, Rose S Tags: Exp Neurol Source Type: research

Sucrose consumption test reveals pharmacoresistant depression-associated behavior in two mouse models of temporal lobe epilepsy.
In conclusion, our findings show for the first time that the SCT is suited for detection of depression-like behavior in mouse models of temporal-lobe epilepsy. Both models might serve as tools to further investigate the neurobiology and pharmacology of epilepsy-associated pharmacoresistant depression. PMID: 25220610 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 11, 2014 Category: Neurology Authors: Klein S, Bankstahl JP, Löscher W, Bankstahl M Tags: Exp Neurol Source Type: research

Repurposing of sodium channel antagonists as potential new anti-myotonic drugs.
Abstract Myotonia is often a painful and disabling symptom which can interfere with daily motor function resulting in significant morbidity. Since myotonic disorders are rare it has generally proved difficult to obtain class I level evidence for anti-myotonic drug efficacy by performing randomized placebo controlled trials. Current treatment guidance is therefore largely based on anecdotal reports and physician experience. Despite the genetic channel heterogeneity of the myotonic disorders the sodium channel antagonists have become the main focus of pharmacological interest. Mexiletine is currently regarded as the...
Source: Experimental Neurology - September 10, 2014 Category: Neurology Authors: Matthews E, Hanna MG Tags: Exp Neurol Source Type: research

Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice.
Abstract Olfactomedin 2 (Olfm2) is a secretory glycoprotein belonging to the family of olfactomedin domain-containing proteins. A previous study has shown that a mutation in OLFM2 is associated with primary open angle glaucoma in Japanese patients. In the present study, we generated Olfm2 deficient mice by replacing the Olfm2 gene with the LacZ gene. The loss of Olfm2 resulted in no gross abnormalities. However, Olfm2 null mice showed reduced exploration, locomotion, olfactory sensitivity, abnormal motor coordination, and anxiety related behavior. The pattern of the Olfm2 gene expression was studied in the brain a...
Source: Experimental Neurology - September 10, 2014 Category: Neurology Authors: Sultana A, Nakaya N, Dong L, Abu-Asab M, Qian H, Tomarev SI Tags: Exp Neurol Source Type: research

The effects of early life stress on the epigenome: From the womb to adulthood and even before.
der E Abstract Exposure to early life stress (ELS), such as childhood abuse and neglect is a well established major risk factor for developing psychiatric and behavioral disorders later in life. Both prenatal and postnatal stressors have been shown to have a long-lasting impact on adult pathological states where the type and timing of the stressor are important factors to consider. There is a growing body of evidence suggesting that epigenetic mechanisms play a major role in the biological embedding of ELS. A number of studies now indicate that the epigenome is responsive to external environmental exposures, inclu...
Source: Experimental Neurology - September 9, 2014 Category: Neurology Authors: Provençal N, Binder E Tags: Exp Neurol Source Type: research

Beta Oscillatory Neurons in the Motor Thalamus of Movement Disorder and Pain Patients.
Abstract Excessive beta oscillations (15-25Hz) in the basal ganglia have been linked to the akineto-rigid symptoms of Parkinson's disease (PD) although it remains unclear whether the underlying mechanism is causative or associative. While a number of studies have reported beta activity in the subthalamic nucleus and globus pallidus internus, relatively little is known about the beta rhythm of the motor thalamus and its relation to movement disorders. To test whether thalamic beta oscillations are related to parkinsonian symptoms, we examined the spectral properties of neuronal activity in the ventral thalamic nucl...
Source: Experimental Neurology - September 6, 2014 Category: Neurology Authors: Basha D, Dostrovsky JO, Lopez Rios AL, Hodaie M, Lozano AM, Hutchison WD Tags: Exp Neurol Source Type: research

Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.
In this study, we use Drosophila photoreceptors to investigate the cell-autonomous effects of neuronal Na(+)/K(+) ATPase. Loss of ATPα, an α subunit of Na(+)/K(+)-ATPase, in photoreceptors through UAS/Gal4-mediated RNAi eliminated the light-triggered depolarization of the photoreceptors, rendering the fly virtually blind in behavioral assays. Intracellular recordings indicated that ATPα knockdown photoreceptors were already depolarized in the dark, which was due to a loss of intracellular K(+). Importantly, ATPα knockdown resulted in the degeneration of photoreceptors in older flies. This degenerati...
Source: Experimental Neurology - September 6, 2014 Category: Neurology Authors: Luan Z, Reddig K, Li HS Tags: Exp Neurol Source Type: research

Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys.
olo T Abstract Subthalamotomy allows a reduction of doses of l-DOPA in dyskinetic patients while its antiparkinsonian benefits are preserved. However, the mechanisms of the potentiation of this response to medication remain to be elucidated. Hence, dopamine D1 and D2 receptors as well as the dopamine transporter were investigated using receptor binding autoradiography. D1 receptor and D2 receptor and preproenkephalin and preprodynorphin mRNA levels were measured by in situ hybridization. Four dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys that underwent unilateral subthalamotom...
Source: Experimental Neurology - August 27, 2014 Category: Neurology Authors: Jourdain VA, Morin N, Morissette M, Grégoire L, Di Paolo T Tags: Exp Neurol Source Type: research

Adenosine A1 receptor stimulation reduces D1 receptor-mediated GABAergic transmission from striato-nigral terminals and attenuates l-DOPA-induced dyskinesia in dopamine-denervated mice.
ri NB Abstract γ-Aminobutyric acid A receptor (GABAAR)-mediated postsynaptic currents were recorded in brain slices from substantia nigra pars reticulate neurons. The selective adenosine A1 receptor (A1R) antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), increased the frequency, but not the amplitude of spontaneous inhibitory post-synaptic currents (IPSCs) in the presence of the dopamine D1 receptor agonist SKF 38393 (SKF) and phosphodiesterase 10A inhibitors (papaverine or AE90074). Under these conditions, DPCPX also increased the amplitude of evoked IPSCs (eIPSCs). The effect of DPCPX was also examin...
Source: Experimental Neurology - August 27, 2014 Category: Neurology Authors: Mango D, Bonito-Oliva A, Ledonne A, Cappellacci L, Petrelli R, Nisticò R, Berretta N, Fisone G, Mercuri NB Tags: Exp Neurol Source Type: research

The prickly, stressful business of burn pain.
PMID: 25173218 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 27, 2014 Category: Neurology Authors: Rau KK, Spears RC, Petruska JC Tags: Exp Neurol Source Type: research

Development and characterization of an aged onset model of Alzheimer's disease in Drosophila melanogaster.
We describe here the creation of an animal model for AD where age is the main factor associated with the development of disease phenotypes. PMID: 25173219 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 27, 2014 Category: Neurology Authors: Mhatre SD, Michelson SJ, Gomes J, Tabb LP, Saunders AJ, Marenda DR Tags: Exp Neurol Source Type: research

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration.
In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using minocycline to treat diabetic neuropathy. PMID: 25158309 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 23, 2014 Category: Neurology Authors: Ali S, Driscoll HE, Newton VL, Gardiner NJ Tags: Exp Neurol Source Type: research

Angiotensin type 1 receptor blockage reduces L-dopa-induced dyskinesia in the 6-OHDA model of Parkinson's disease. Involvement of Vascular Endothelial Growth Factor and interleukin-1β
In this study, we investigated whether manipulation of brain RAS is effective in preventing LID. Blocking AT1 receptors with candesartan significantly reduces LID in the 6-OHDA rat model. Chronic dopaminergic denervation induces an increase in striatal levels of VEGF and IL-1β. Dyskinetic animals showed significantly higher levels of VEGF and IL-1β in the lateral striatum and the substantia nigra, as revealed by western blot and real time-PCR analysis. Interestingly, animals treated with both candesartan and L-dopa displayed significantly lower levels of VEGF, IL-1β and dyskinesia than those treated with L-d...
Source: Experimental Neurology - August 23, 2014 Category: Neurology Authors: Muñoz A, Garrido-Gil P, Dominguez-Meijide A, Labandeira-Garcia JL Tags: Exp Neurol Source Type: research

Commentary on Myers et al.: Growing role of the innate immunity receptor CD36 in central nervous system diseases.
Abstract Activation of innate immunity by sterile inflammation has emerged as a key event in selected CNS diseases, with a defining impact on all stages of the pathological process. Due to its multiple functions and assembly with other pattern recognition receptors, the innate immunity receptor CD36 has been implicated in a wide variety of brain pathologies, ranging from acute brain injury to neurodegeneration. However, the role of CD36 is complex involving both tissue destruction, related mainly to oxidative stress and inflammation, and beneficial reparative effects due to the involvement of CD36 in tissue repair...
Source: Experimental Neurology - August 22, 2014 Category: Neurology Authors: Garcia-Bonilla L, Park L, Iadecola C Tags: Exp Neurol Source Type: research

The mixed blessing of treating symptoms in acute vestibular failure - Evidence from a 4-aminopyridine experiment.
In conclusion, this study confirms the hypothesis that early pharmacological abatement of vestibular symptoms impedes VC. PMID: 25157903 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 22, 2014 Category: Neurology Authors: Beck R, Günther L, Xiong G, Potschka H, Böning G, Bartenstein P, Brandt T, Jahn K, Dieterich M, Strupp M, la Fougère C, Zwergal A Tags: Exp Neurol Source Type: research

Special issue on amyotrophic lateral sclerosis.
PMID: 25158310 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 22, 2014 Category: Neurology Authors: Traynor BJ, Cleveland DW Tags: Exp Neurol Source Type: research

Agrin requires specific proteins to selectively activate γ-aminobutyric acid neurons for pain suppression.
Agrin requires specific proteins to selectively activate γ-aminobutyric acid neurons for pain suppression. Exp Neurol. 2014 Aug 21; Authors: Erasso D, Tender G, Levitt R, Cui JG Abstract Agrin, a heparan sulfate proteoglycan functioning as a neuro-muscular junction inducer, has been shown to inhibit neuropathic pain in sciatic nerve injury rat models, via phosphorylation of N-Methyl-d-aspartate receptor NR1 subunits in gamma-aminobutyric acid neurons. However, its effects on spinal cord injury-induced neuropathic pain, a debilitating syndrome frequently encountered after various spine traumas, a...
Source: Experimental Neurology - August 21, 2014 Category: Neurology Authors: Erasso D, Tender G, Levitt R, Cui JG Tags: Exp Neurol Source Type: research

Osteopontin Expression in Acute Immune Response Mediates Hippocampal Synaptogenesis and Adaptive Outcome Following Cortical Brain Injury.
This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1-2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived...
Source: Experimental Neurology - August 20, 2014 Category: Neurology Authors: Chan JL, Reeves TM, Phillips LL Tags: Exp Neurol Source Type: research

Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration.
n A Abstract Despite highly active antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) are still highly prevalent. Direct neurotoxicity of microglia activated by HIV-infected monocytes independent from viral replication may account for this observation. To investigate underlying molecular and viral determinants, human monocytoid cells (U937) transduced with HIV-particles were co-cultured with primary human microglia or astrocytes. Using genetically-engineered HIV-particles key steps of infection were examined. Levels of pro-inflammatory/neurotoxic cytokines were investigated in co-culture supern...
Source: Experimental Neurology - August 19, 2014 Category: Neurology Authors: Faissner S, Ambrosius B, Schanzmann I, Grewe B, Potthoff A, Münch J, Sure U, Gramberg T, Wittmann S, Brockmeyer N, Uberla K, Gold R, Grunwald T, Chan A Tags: Exp Neurol Source Type: research

A pivotal role of nonmuscle myosin II during microglial activation.
In conclusion, we propose a pivotal role of NM II in cytoskeleton organization during microglial activation. This is of great importance to understand the mechanisms of microglial action in inflammatory CNS diseases. PMID: 25150163 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 18, 2014 Category: Neurology Authors: Janßen S, Gudi V, Prajeeth CK, Singh V, Stahl K, Heckers S, Skripuletz T, Pul R, Trebst C, Tsiavaliaris G, Stangel M Tags: Exp Neurol Source Type: research

Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation.
Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation. Exp Neurol. 2014 Aug 16; Authors: Müller GJ, Hasseldam H, Rasmussen RS, Johansen FF Abstract Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI...
Source: Experimental Neurology - August 16, 2014 Category: Neurology Authors: Müller GJ, Hasseldam H, Rasmussen RS, Johansen FF Tags: Exp Neurol Source Type: research

Role of striatal NMDA receptor subunits in a model of paroxysmal dystonia.
r A Abstract Dystonia is a movement disorder in which abnormal plasticity in the basal ganglia has been hypothesized to play a critical role. In a model of paroxysmal dystonia, the dt(sz) mutant hamster, previous studies indicated striatal dysfunctions, including an increased long-term potentiation (LTP). Beneficial effects were exerted by subunit-unspecific antagonists at NMDA receptors, which blocked LTP. NR2B subtype selective antagonists aggravated dystonia after systemic treatment in dt(sz) hamsters, suggesting that beneficial effects involved the NR2A receptor subtype. In the present study, NVP-AAM077, an an...
Source: Experimental Neurology - August 16, 2014 Category: Neurology Authors: Avchalumov Y, Sander SE, Richter F, Porath K, Hamann M, Bode C, Kirschstein T, Köhling R, Richter A Tags: Exp Neurol Source Type: research

'Not-so-minor' stroke: Lasting psychosocial consequences of anterior cingulate cortical ischemia in the rat.
Abstract Patients with small, non-debilitating strokes often report a reduction in quality of life due to persistent cognitive and emotional alterations. Stroke may directly damage limbic circuitry resulting in an impaired stress response, however the possibility that this may in part explain the prevalence of stroke comorbidity with mood disorders has yet to be determined. Here we systematically examine psychosocial consequences of prefrontal lesions targeting the left anterior cingulate cortex (ACC) using hormone assays and a behavioral test battery in adult rats to probe whether a small stroke could alter stres...
Source: Experimental Neurology - August 15, 2014 Category: Neurology Authors: Hewlett KA, Kelly MH, Corbett D Tags: Exp Neurol Source Type: research

Epigenetics and sex differences in the brain: A genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice.
Abstract Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized ...
Source: Experimental Neurology - August 14, 2014 Category: Neurology Authors: Shen EY, Ahern TH, Cheung I, Straubhaar J, Dincer A, Houston I, de Vries GJ, Akbarian S, Forger NG Tags: Exp Neurol Source Type: research

Impaired Src signaling and post-synaptic actin polymerization in Alzheimer's disease mice hippocampus - Linking NMDA receptors and the reelin pathway.
In this study we analyzed the changes in GluN2B subunit phosphorylation and the levels of proteins involved in Src related signaling pathways linking the Tyr kinase to actin cytoskeleton polymerization, namely reelin, disabled-1 (Dab1) and cortactin, in hippocampal and cortical homogenates obtained from the triple transgenic mouse model of AD (3xTg-AD) that shows progression of pathology as a function of age versus age-matched wild-type mice. Moreover, we evaluated regional post-synaptic actin polymerization using phalloidin labeling in hippocampal slices. Young (3month-old) 3xTg-AD male mice hippocampus exhibited decrease...
Source: Experimental Neurology - August 13, 2014 Category: Neurology Authors: Mota SI, Ferreira IL, Valero J, Ferreiro E, Carvalho AL, Oliveira CR, Rego AC Tags: Exp Neurol Source Type: research

MicroRNAs: small molecules with big roles in neurodevelopment and diseases.
Abstract MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that play important roles in the development and functions of the brain. Extensive studies have revealed critical roles for miRNAs in brain development and function. Dysregulation or altered expression of miRNAs is associated with abnormal brain development and pathogenesis of neurodevelopmental diseases. This review serves to highlight the versatile roles of these small RNA molecules in normal brain development and their association with neurodevelopmental disorders, in particular, two closely related neuropsychiatric disorders of neurodeve...
Source: Experimental Neurology - August 12, 2014 Category: Neurology Authors: Sun E, Shi Y Tags: Exp Neurol Source Type: research

A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF.
In conclusion, autograft-based repair combined with gene therapy for three of the six growth factors investigated (BDNF, GDNF, NGF) showed considerable promise since these factors enhanced modality specific axon outgrowth in autografts. The remarkable and selective effects of BDNF, GDNF and NGF on motor or sensory regeneration will be exploited in future experiments that aim to carefully regulate their temporal and spatial expression since this has the potential to overcome the adverse effects on long-distance regeneration observed after uncontrolled delivery. PMID: 25128265 [PubMed - as supplied by publisher] (Source...
Source: Experimental Neurology - August 12, 2014 Category: Neurology Authors: Hoyng SA, De Winter F, Gnavi S, de Boer R, Boon LI, Korvers LM, Tannemaat MR, Malessy MJ, Verhaagen J Tags: Exp Neurol Source Type: research