Use of human stem cells in Huntington disease modeling and translational research.
Abstract Huntington disease (HD) is a devastating neurological disorder caused by an extended CAG repeat in exon 1 of the gene that encodes the huntingtin (HTT) protein. HD pathology involves a loss of striatal medium spiny neurons (MSNs) and progressive neurodegeneration affects the striatum and other brain regions. Because HTT is involved in multiple cellular processes, the molecular mechanisms of HD pathogenesis should be investigated on multiple levels. On the cellular level, in vitro stem cell models, such as induced pluripotent stem cells (iPSCs) derived from HD patients and HD embryonic stem cells (ESCs), h...
Source: Experimental Neurology - January 27, 2016 Category: Neurology Authors: Golas MM, Sander B Tags: Exp Neurol Source Type: research

Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease.
This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD. PMID: 26825854 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 26, 2016 Category: Neurology Authors: Garcia-Miralles M, Ooi J, Bardile CF, Tan LJ, George M, Drum CL, Lin RY, Hayden MR, Pouladi MA Tags: Exp Neurol Source Type: research

Respiratory outcomes after mid-cervical transplantation of embryonic medullary cells in rats with cervical spinal cord injury.
Abstract Respiratory motor output after cervical spinal cord injury (cSCI) is profoundly influenced by spinal serotonin. We hypothesized that intraspinal transplantation of embryonic midline brainstem (MB) cells rich in serotonergic raphé neurons would improve respiratory outcomes after cSCI. One week after hemisection of the 2nd cervical segment (C2Hx) a suspension of either embryonic (E14) MB cells, fetal spinal cord cells (FSC), or media only (sham) was delivered to the dorsal C3 spinal cord of adult male rats. Six weeks later, ventilation was evaluated using plethysmography; phrenic nerve activity was e...
Source: Experimental Neurology - January 22, 2016 Category: Neurology Authors: Dougherty BJ, Gonzalez-Rothi EJ, Lee KZ, Ross HH, Reier PJ, Fuller DD Tags: Exp Neurol Source Type: research

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury.
Abstract Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months. Within one week after injury, rats developed consistent forepaw pain-rel...
Source: Experimental Neurology - January 22, 2016 Category: Neurology Authors: Lee-Kubli CA, Ingves M, Henry KW, Shiao R, Collyer E, Tuszynski MH, Campana WM Tags: Exp Neurol Source Type: research

Anti-glycan antibodies halt axon regeneration in a model of guillain Barrè syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK-dependent inactivation of CRMP-2.
Anti-glycan antibodies halt axon regeneration in a model of guillain Barrè syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK-dependent inactivation of CRMP-2. Exp Neurol. 2016 Jan 21; Authors: Salvador VR, Heredia F, Berardo A, Palandri A, Wojnacki J, Vivinetto AL, Sheikh KA, Caceres A, Lopez PH Abstract Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derive...
Source: Experimental Neurology - January 21, 2016 Category: Neurology Authors: Salvador VR, Heredia F, Berardo A, Palandri A, Wojnacki J, Vivinetto AL, Sheikh KA, Caceres A, Lopez PH Tags: Exp Neurol Source Type: research

Postnatal glucocorticoid-induced hypomyelination, gliosis, and neurologic deficits are dose-dependent, preparation-specific, and reversible.
PMID: 26795086 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 18, 2016 Category: Neurology Authors: Malaeb SN, Stonestreet BS Tags: Exp Neurol Source Type: research

The use of the rat as a model for studying peripheral nerve regeneration and sprouting after complete and partial nerve injuries.
Abstract Rat models of complete and partial injuries are the most frequently used models for analysis of the cellular and molecular processes of nerve regeneration and axon sprouting. Studies of nerve regeneration and axon sprouting after complete and partial nerve injuries, respectively, are reviewed. Special consideration is made of the peripheral nerves chosen for the studies and the outcome measures that were utilized in the studies. The studies have made important contributions to our knowledge of the degenerative and regenerative processes that occur after the peripheral nerve injuries, why functional recove...
Source: Experimental Neurology - January 18, 2016 Category: Neurology Authors: Gordon T, Borschel GH Tags: Exp Neurol Source Type: research

Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses.
Abstract Central nervous system (CNS) regeneration is restricted by both the lack of neurotrophic responses and the presence of inhibitory factors. As of yet, a common mediator of these two pathways has not been identified. Microtubule dynamics is responsible for several key processes after CNS injuries: intracellular trafficking of receptors for neurotrophic factors, axonal retraction by inhibitory factors, and secondary tissue damages by inflammation and scarring. Kinases regulating microtubule organization, such as Cdk5 or GSK3β, may play pivotal roles during CNS recovery, but the molecular mechanisms rema...
Source: Experimental Neurology - January 18, 2016 Category: Neurology Authors: Nagai J, Owada K, Kitamura Y, Goshima Y, Ohshima T Tags: Exp Neurol Source Type: research

Systemic inflammation affects reperfusion following transient cerebral ischaemia.
Abstract Reperfusion after stroke is critical for improved patient survival and recovery and can be achieved clinically through pharmacological (recombinant tissue plasminogen activator) or physical (endovascular intervention) means. Yet these approaches remain confined to a small percentage of stroke patients, often with incomplete reperfusion, and therefore there is an urgent need to learn more about the mechanisms underlying the no-reflow phenomenon that prevents restoration of adequate microvascular perfusion. Recent evidence suggests systemic inflammation as an important contributor to no-reflow and to furthe...
Source: Experimental Neurology - January 18, 2016 Category: Neurology Authors: Burrows F, Haley MJ, Scott E, Coutts G, Lawrence CB, Allan SM, Schiessl I Tags: Exp Neurol Source Type: research

Neuroinflammation in primary blast neurotrauma: Time course and prevention by torso shielding.
In this study, we investigated the temporal dynamics of microglial activation in the brain of mice exposed to mild-moderate blast in a shock tube. Because, in our previous work, we had found that torso shielding with rigid Plexiglas attenuates traumatic axonal injury in the brain, we also evaluated neuroinflammatory microglial responses in animals with torso protection at 7days post blast injury. Because of the prominent involvement of the visual system in blast TBI in rodents, activated microglial cells were counted in the optic tract at various time points post-injury with stereological methods. Cell counts (activated mi...
Source: Experimental Neurology - January 16, 2016 Category: Neurology Authors: Xu L, Schaefer ML, Linville RM, Aggarwal A, Mbuguiro W, Wester BA, Koliatsos VE Tags: Exp Neurol Source Type: research

Generation of Highly Enriched V2a Interneurons from Mouse Embryonic Stem Cells.
In this study, we employed a genetic strategy to obtain large quantities of highly enriched mouse embryonic stem cell (ESC)-derived V2a INs, an excitatory glutamatergic IN population that is defined by expression of the homeodomain protein Chx10 during development. Puromycin N-acetyltransferase expression was driven by the native gene regulatory elements of Chx10 in the transgenic ESC line, resulting in positive selection of V2a INs after induction and treatment with puromycin. Directly after selection, approximately 80% of cells are Chx10(+), with 94% Lhx3(+); after several weeks, cultures remain free of proliferative cel...
Source: Experimental Neurology - January 16, 2016 Category: Neurology Authors: Iyer NR, Huettner JE, Butts JC, Brown CR, Sakiyama-Elbert SE Tags: Exp Neurol Source Type: research

The role of endoplasmic reticulum stress in hippocampal insulin resistance.
Abstract Metabolic syndrome, which includes hypertension, hyperglycemia, obesity, insulin resistance, and dyslipidemia, has a negative impact on cognitive health. Endoplasmic reticulum (ER) stress is activated during metabolic syndrome, however it is not known which factor associated with metabolic syndrome contributes to this stress. ER stress has been reported to play a role in the development of insulin resistance in peripheral tissues. The role of ER stress in the development of insulin resistance in hippocampal neurons is not known. In the current study, we investigated ER stress in the hippocampus of 3 diffe...
Source: Experimental Neurology - January 13, 2016 Category: Neurology Authors: Sims-Robinson C, Bakeman A, Glasser R, Boggs J, Pacut C, Feldman EL Tags: Exp Neurol Source Type: research

Submembranous molecular complex stabilizes nodes of Ranvier.
Abstract Rapid action potential propagation along myelinated axons requires voltage-gated Na(+) (Nav) channel clustering at nodes of Ranvier. At paranodes flanking nodes, myelinating glial cells interact with axons to form junctions. The regions next to the paranodes called juxtaparanodes are characterized by high concentrations of voltage-gated K(+) channels. Paranodal axoglial junctions function as barriers to restrict the position of these ion channels. These specialized domains along the myelinated nerve fiber are formed by multiple molecular mechanisms including interactions between extracellular matrix, cell...
Source: Experimental Neurology - January 13, 2016 Category: Neurology Authors: Susuki K, Otani Y, Rasband MN Tags: Exp Neurol Source Type: research

Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS).
In this study, we evaluate inflammatory and glial responses near NMJs in the limb muscle collected from a rat model of familial ALS (SOD1(G93A) transgenic rats) during disease progression and following hMSC-GDNF transplantation. Muscle samples were collected from pre-symptomatic, symptomatic, and end-stage animals. A significant increase in the expression of microglial inflammatory markers (CD11b and CD68) occurred in the skeletal muscle of symptomatic and end-stage SOD1(G93A) rats. Inflammation was confirmed by ELISA for inflammatory cytokines interleukin 1 β (IL-1β) and tumor necrosis factor-α (TNF-&alpha...
Source: Experimental Neurology - January 13, 2016 Category: Neurology Authors: Dyke JM, Smit-Oistad IM, Macrandar C, Krakora D, Meyer MG, Suzuki M Tags: Exp Neurol Source Type: research

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.
This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Ta...
Source: Experimental Neurology - January 7, 2016 Category: Neurology Authors: Thyrion L, Raedt R, Portelli J, Van Loo P, Wadman WJ, Glorieux G, Lambrecht B, Janssens S, Vonck K, Boon P Tags: Exp Neurol Source Type: research

Enduring Changes in Tonic GABAA Receptor Signaling in Dentate Granule Cells After Controlled Cortical Impact Brain Injury in Mice.
Abstract Changes in functional GABAAR signaling in hippocampus have previously been evaluated using pre-clinical animal models of either diffuse brain injury or extreme focal brain injury that precludes measurement of cells located ipsilateral to injury. As a result, there is little information about the status of functional GABAAR signaling in dentate granule cells (DGCs) located ipsilateral to focal brain injury, where significant cellular changes have been documented. We used whole-cell patch-clamp recordings from hippocampal slices to measure changes in GABAARs in dentate granule cells (DGCs) at 1-2 weeks and ...
Source: Experimental Neurology - January 6, 2016 Category: Neurology Authors: Boychuk JA, Butler CR, Halmos KC, Smith BN Tags: Exp Neurol Source Type: research

Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord.
In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -β, IL-1β) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2...
Source: Experimental Neurology - January 6, 2016 Category: Neurology Authors: Hu JG, Shi LL, Chen YJ, Xie XM, Zhang N, Zhu AY, Jiang ZS, Feng YF, Zhang C, Xi J, Lü HZ Tags: Exp Neurol Source Type: research

Chronic stress regulates NG2(+) cell maturation and myelination in the prefrontal cortex through induction of death receptor 6.
Abstract Chronic stress significantly affects neuron morphometry and function in the prefrontal cortex, a brain region controlling cognition and emotion. However, whether and how chronic stress regulates the maturation of NG2-expressing oligodendrocyte precursor cells (NG2(+) cells) and the importance of these changes remained unknown. Here, we report that exposing adult mice to chronic stress results in NG2(+) cells atrophy and myelination arrested in the medial prefrontal cortex (mPFC), and impaired mPFC-dependent functions. These alterations, are phenocopied by overexpression of death receptor 6 (DR6) in NG2(+)...
Source: Experimental Neurology - January 6, 2016 Category: Neurology Authors: Yang Y, Zhang Y, Luo F, Li B Tags: Exp Neurol Source Type: research

Introduction to special issue on traumatic brain injury.
PMID: 26694827 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 27, 2015 Category: Neurology Authors: Symes A, Diaz-Arrastia R Tags: Exp Neurol Source Type: research

CNS consequences of perinatal peripheral injuries.
PMID: 26689323 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 24, 2015 Category: Neurology Authors: Erzurumlu RS Tags: Exp Neurol Source Type: research

Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway.
Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway. Exp Neurol. 2015 Dec 11; Authors: Xia C, Shen S, Hashmi F, Qiao LY Abstract Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent neurons in the dorsal root ganglia (DRG) plays essen...
Source: Experimental Neurology - December 11, 2015 Category: Neurology Authors: Xia C, Shen S, Hashmi F, Qiao LY Tags: Exp Neurol Source Type: research

Subcortical evoked activity and motor enhancement in Parkinson's disease.
Abstract Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related p...
Source: Experimental Neurology - December 11, 2015 Category: Neurology Authors: Anzak A, Tan H, Pogosyan A, Khan S, Javed S, Gill SS, Ashkan K, Akram H, Foltynie T, Limousin P, Zrinzo L, Green AL, Aziz T, Brown P Tags: Exp Neurol Source Type: research

Buspirone requires the intact nigrostriatal pathway to reduce the activity of the subthalamic nucleus via 5-HT1A receptors.
This study examined the effect of buspirone on STN neuron activity. Cell-attached recordings in parasagittal slices from naïve rats showed that whilst serotonin excited the majority of STN neurons, buspirone showed an inhibitory main effect but only in a 27% of the studied cells which was prevented by the 5-HT1A receptor selective antagonist WAY-100,635. Conversely, single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with L-DOPA, 6-OHDA lesioned and lesioned treated with L-DOPA (dyskinetic) rats. In control animals, systemic-buspiron...
Source: Experimental Neurology - December 11, 2015 Category: Neurology Authors: Sagarduy A, Llorente J, Miguelez C, Morera-Herreras T, Ruiz-Ortega JA, Ugedo L Tags: Exp Neurol Source Type: research

Rescuing Effects of RXR Agonist Bexarotene on Aging-related Synapse Loss Depend on Neuronal LRP1.
Abstract Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (...
Source: Experimental Neurology - December 11, 2015 Category: Neurology Authors: Tachibana M, Shinohara M, Yamazaki Y, Liu CC, Rogers J, Bu G, Kanekiyo T Tags: Exp Neurol Source Type: research

Involvement of aberrant calcium signalling in herpetic neuralgia.
Abstract Alpha-herpesviruses, herpes simplex viruses (HSV) and varicella zoster virus (VZV), are pathogens of the peripheral nervous system. After primary infection, these viruses establish latency within sensory ganglia, while retaining the ability to reactivate. Reactivation of VZV results in herpes zoster, a condition characterized by skin lesions that leads to post-herpetic neuralgia. Recurrent reactivations of HSV, which cause mucocutaneous lesions, may also result in neuralgia. During reactivation of alpha-herpesviruses, satellite glial cells (SGCs), which surround neurons in sensory ganglia, become infected...
Source: Experimental Neurology - December 9, 2015 Category: Neurology Authors: Warwick RA, Hanani M Tags: Exp Neurol Source Type: research

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.
om VJ Abstract Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)(+) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)(-) and some contain detectable dopamine decarboxylase (DDC), suggestin...
Source: Experimental Neurology - December 2, 2015 Category: Neurology Authors: Hou S, Carson DM, Wu D, Klaw MC, Houlé JD, Tom VJ Tags: Exp Neurol Source Type: research

Introduction to glyco-neuroscience.
PMID: 26652599 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - December 1, 2015 Category: Neurology Authors: Kamiguchi H, Kadomatsu K Tags: Exp Neurol Source Type: research

Drosophila models of neurologic disease.
PMID: 26566006 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - November 15, 2015 Category: Neurology Authors: Wu MN, Lloyd TE Tags: Exp Neurol Source Type: research

Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease.
In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 μg / 4 μl) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 hours after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic teminals inherent in the striatum, and attenuated ...
Source: Experimental Neurology - November 7, 2015 Category: Neurology Authors: Sasaki T, Liu K, Agari T, Yasuhara T, Morimoto J, Okazaki M, Takeuchi H, Toyoshima A, Sasada S, Shinko A, Kondo A, Kameda M, Miyazaki I, Asanuma M, Borlongan CV, Nishibori M, Date I Tags: Exp Neurol Source Type: research

Dysfunction in Amygdala-Prefrontal Plasticity and Extinction-Resistant Avoidance: A model for anxiety disorder vulnerability.
Abstract Individuals exhibiting an anxiety disorder are believed to possess an innate vulnerability that makes them susceptible to the disorder. Anxiety disorders are also associated with abnormalities in the interconnected brain regions of the amygdala and prefrontal cortex (PFC). However, the link between anxiety vulnerability and amygdala-PFC dysfunction is currently unclear. Accordingly, the present study sought to determine if innate dysfunction within the amygdala to PFC projection underlies the susceptibility to develop anxiety-like behavior, using an anxiety vulnerable rodent model. The inbred Wistar Kyoto...
Source: Experimental Neurology - November 4, 2015 Category: Neurology Authors: Fragale JE, Khariv V, Gregor DM, Smith IM, Jiao X, Elkabes S, Servatius RJ, Pang KC, Beck KD Tags: Exp Neurol Source Type: research

Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.
Abstract Oxaliplatin (OXA) is the common and extremely potent anti-advanced colorectal cancer chemotherapeutic. Accumulating evidence reveals that OXA evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome and dose-limiting adverse effects is poorly understood. It is well known that cyclooxygenase-2 (COX-2) as well as phosphoinositide 3-kinase (PI3K)/Akt signaling mediate the neuropathic pain. But it is still unclear whether COX-2 or PI3K/Akt signaling participates in the regulation of OXA-induced hypersensitivity, as well as the linkage between COX-2 and PI3K/Akt signaling...
Source: Experimental Neurology - November 3, 2015 Category: Neurology Authors: Jiang SP, Zhang ZD, Kang LM, Wang QH, Zhang L, Chen HP Tags: Exp Neurol Source Type: research

Sirtuin-2 mediates male specific neuronal injury following experimental cardiac arrest through activation of TRPM2 ion channels.
CONCLUSIONS: In summary, we observed a male specific activation of SIRT2 that contributes to neuronal injury and functional deficits after ischemia specifically in males. These results are consistent with a role of SIRT2 in activating TRPM2 following global ischemia in a sex specific manner. These results support the growing body of literature showing that oxidative stress mechanisms predominate in males and converge on TRPM2 activation as a mediator of cell death. PMID: 26522013 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 30, 2015 Category: Neurology Authors: Shimizu K, Quillinan N, Orfila JE, Herson PS Tags: Exp Neurol Source Type: research

Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.
Abstract To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7days after the insult. Neuroprotection was associated ...
Source: Experimental Neurology - October 27, 2015 Category: Neurology Authors: Amantea D, Certo M, Petrelli F, Tassorelli C, Micieli G, Corasaniti MT, Puccetti P, Fallarino F, Bagetta G Tags: Exp Neurol Source Type: research

JNK-mediated activation of ATF2 contributes to dopaminergic neurodegeneration in the MPTP mouse model of Parkinson's disease.
In this study, we confirm that JNK but not p38 is activated in dopaminergic neurons after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxication. Furthermore, within the dopaminergic neurons of the substantia nigra in MPTP-treated mice, JNK2/3 phosphorylates threonine 69 (Thr69) of Activating transcription factor-2 (ATF2), a transcription factor of the ATF/CREB family, whereas the phosphorylation of Thr71 is constitutive and remains unchanged. The increased phosphorylation of ATF2 on Thr69 by JNK in the MPTP mouse model suggests a functional relationship between the transcriptional activation of ATF2 and dopamine...
Source: Experimental Neurology - October 26, 2015 Category: Neurology Authors: Huang Q, Du X, He X, Yu Q, Hu K, Breitwieser W, Shen Q, Ma S, Li M Tags: Exp Neurol Source Type: research

Amyloid-β suppresses AMP-activated protein kinase (AMPK) signaling and contributes to α-synuclein-induced cytotoxicity.
Amyloid-β suppresses AMP-activated protein kinase (AMPK) signaling and contributes to α-synuclein-induced cytotoxicity. Exp Neurol. 2015 Oct 26; Authors: Lin CL, Cheng YS, Li HH, Chiu PY, Chang YT, Ho YJ, Lai TJ Abstract Dementia with Lewy bodies (DLB) is a neurodegenerative disorder caused by abnormal accumulation of Lewy bodies, which are intracellular deposits composed primarily of aggregated α-synuclein (αSyn). Although αSyn has been strongly implicated to induce neurotoxicity, overexpression of wild-type αSyn is shown to be insufficient to trigger formation of p...
Source: Experimental Neurology - October 26, 2015 Category: Neurology Authors: Lin CL, Cheng YS, Li HH, Chiu PY, Chang YT, Ho YJ, Lai TJ Tags: Exp Neurol Source Type: research

The molecular physiology of the axo-myelinic synapse.
Abstract Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons in vitro. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by G...
Source: Experimental Neurology - October 26, 2015 Category: Neurology Authors: Micu I, Plemel JR, Lachance C, Proft J, Jansen AJ, Cummins K, van Minnen J, Stys PK Tags: Exp Neurol Source Type: research

Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.
Abstract Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebral...
Source: Experimental Neurology - October 26, 2015 Category: Neurology Authors: Srivastava AK, Bulte CA, Shats I, Walczak P, Bulte JW Tags: Exp Neurol Source Type: research

Phosphodiesterase-5 inhibition promotes remyelination by MCP-1/CCR-2 and MMP-9 regulation in a cuprizone-induced demyelination model.
Peixoto CA PMID: 26515692 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 26, 2015 Category: Neurology Authors: de Santana Nunes AK, Rapôso C, de Oliveira WH, Thomé R, Verinaud L, Tovar-Moll F, Peixoto CA Tags: Exp Neurol Source Type: research

BAG2 expression dictates a functional intracellular switch between the p38-dependent effects of nicotine on tau phosphorylation levels via the α7 nicotinic receptor.
BAG2 expression dictates a functional intracellular switch between the p38-dependent effects of nicotine on tau phosphorylation levels via the α7 nicotinic receptor. Exp Neurol. 2015 Oct 20; Authors: de Oliveira AS, Santiago FE, Balioni LF, de Fatima Ramires Ferrari M, Almeida MC, Carrettiero DC Abstract The histopathological hallmarks present in Alzheimer's disease (AD) brain are plaques of Aβ peptide, neurofibrillary tangles of hyperphosphorylated tau protein, and a reduction in nicotinic acetylcholine receptor (nAChR) levels. The role of nAChRs in AD is particularly controversial. Tau pr...
Source: Experimental Neurology - October 20, 2015 Category: Neurology Authors: de Oliveira AS, Santiago FE, Balioni LF, de Fatima Ramires Ferrari M, Almeida MC, Carrettiero DC Tags: Exp Neurol Source Type: research

Cortical electroconvulsive stimulation alleviates breeding-induced prepulse inhibition deficit in rats.
PMID: 26476178 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 14, 2015 Category: Neurology Authors: John N, Theilmann W, Frieling H, Krauss JK, Alam M, Schwabe K, Brandt C Tags: Exp Neurol Source Type: research

Thidoredxin-2 overexpression fails to rescue chronic high calorie diet induced hippocampal dysfunction.
Abstract A high calorie diet (HCD) diet can impair hippocampal synaptic plasticity and cognitive function in animal models. Mitochondrial thioredoxin 2 (TRX-2) is critical for maintaining intracellular redox status, but whether it can protect against HCD-induced impairment of synaptic plasticity is unknown. We found that levels of TRX-2 are reduced in the hippocampus of wild type mice maintained for 8months on a HCD, and that the mice on the HCD exhibit impaired hippocampal synaptic plasticity (long-term potentiation at CA1 synapses) and cognitive function (novel object recognition). Transgenic mice overexpressing...
Source: Experimental Neurology - October 14, 2015 Category: Neurology Authors: Liu Y, Yang Y, Dong H, Cutler RG, Strong R, Mattson MP Tags: Exp Neurol Source Type: research

The transition from naïve to primed nociceptive state: A novel wind-up protocol in mice.
The transition from naïve to primed nociceptive state: A novel wind-up protocol in mice. Exp Neurol. 2015 Oct 3; Authors: Ziv NY, Tal M, Shavit Y Abstract Wind-up (WU) is a progressive, frequency-dependent facilitation of spinal cord neurons in response to repetitive nociceptive stimulation of constant intensity. We identified a new WU-associated phenomenon in naïve mice (not exposed to noxious stimulation immediately prior to WU stimulation), which were subjected to a novel experimental protocol composed of three consecutive trains of WU stimulation. The 1st train produced a typical linear ...
Source: Experimental Neurology - October 3, 2015 Category: Neurology Authors: Ziv NY, Tal M, Shavit Y Tags: Exp Neurol Source Type: research

Ziram, a pesticide associated with increased risk for Parkinson's disease, differentially affects the presynaptic function of aminergic and glutamatergic nerve terminals at the Drosophila neuromuscular junction.
Abstract Multiple populations of aminergic neurons are affected in Parkinson's disease (PD), with serotonergic and noradrenergic loci responsible for some non-motor symptoms. Environmental toxins, such as the dithiocarbamate fungicide ziram, significantly increase the risk of developing PD and the attendant spectrum of both motor and non-motor symptoms. The mechanisms by which ziram and other environmental toxins increase the risk of PD, and the potential effects of these toxins on aminergic neurons, remain unclear. To determine the relative effects of ziram on the synaptic function of aminergic versus non-aminerg...
Source: Experimental Neurology - October 3, 2015 Category: Neurology Authors: Martin CA, Myers KM, Chen A, Martin NT, Barajas A, Schweizer FE, Krantz DE Tags: Exp Neurol Source Type: research

Brainstem node for loss of consciousness due to GABAA receptor-active anesthetics.
Abstract The molecular agents that induce loss of consciousness during anesthesia are classically believed to act by binding to cognate transmembrane receptors widely distributed in the CNS and critically suppressing local processing and network connectivity. However, previous work has shown that microinjection of anesthetics into a localized region of the brainstem mesopontine tegmentum (MPTA) rapidly and reversibly induces anesthesia in the absence of global spread. This implies that functional extinction is determined by neural pathways rather than vascular distribution of the anesthetic agent. But does clinica...
Source: Experimental Neurology - October 2, 2015 Category: Neurology Authors: Minert A, Devor M Tags: Exp Neurol Source Type: research

Overexpression of the monocyte chemokine CCL2 in dorsal root ganglion neurons causes a conditioning-like increase in neurite outgrowth and does so via a STAT3 dependent mechanism.
Abstract Neuroinflammation plays a critical role in the regeneration of peripheral nerves following axotomy. An injury to the sciatic nerve leads to significant macrophage accumulation in the L5 DRG, an effect not seen when the dorsal root is injured. We recently demonstrated that this accumulation around axotomized cell bodies is necessary for a peripheral conditioning lesion response to occur. Here we asked whether overexpression of the monocyte chemokine CCL2 specifically in DRG neurons of uninjured mice is sufficient to cause macrophage accumulation and to enhance regeneration or whether other injury-derived s...
Source: Experimental Neurology - September 29, 2015 Category: Neurology Authors: Niemi JP, DeFrancesco-Lisowitz A, Cregg J, Howarth M, Zigmond RE Tags: Exp Neurol Source Type: research

Long term study of deoxyribozyme administration to XT-1 mRNA promotes corticospinal tract regeneration and improves behavioral outcome after spinal cord injury.
PMID: 26428904 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 28, 2015 Category: Neurology Authors: Koenig B, Pape D, Chao O, Bauer J, Grimpe B Tags: Exp Neurol Source Type: research

Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration.
Abstract We previously demonstrated that mice with reduced expression of the vesicular monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the catecholamine-producing neurons of the substantia nigra pars compacta and locus ceruleus and exhibit motor disturbances and depressive-like behavior. In this work, we investigated the effects of reduced vesicular transport on the function and viability of serotonin neurons in these mice. Adult (2months of age), VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as measured by fast scan cyclic voltammetry. We observed changes in s...
Source: Experimental Neurology - September 28, 2015 Category: Neurology Authors: Alter SP, Stout KA, Lohr KM, Taylor TN, Shepherd KR, Wang M, Guillot TS, Miller GW Tags: Exp Neurol Source Type: research

Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis.
Abstract Human immunodeficiency virus (HIV) rapidly penetrates into the brain and establishes a persistent infection of macrophages/microglia. Activation of these cells by HIV results in the secretion of soluble factors that destabilize neuronal calcium homeostasis, encourage oxidative stress and result in neural damage. This damage is thought to underlie the cognitive-motor dysfunction that develops in many HIV-infected patients. Studies have suggested that neurotrophins may protect neurons from the toxic effects of HIV-associated proteins. To better understand the pathogenic mechanisms and the neuroprotective po...
Source: Experimental Neurology - September 27, 2015 Category: Neurology Authors: Meeker RB, Poulton W, Clary G, Schriver M, Longo FM Tags: Exp Neurol Source Type: research

Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.
In this study, an analysis of TSC morphology and number was performed in relation to NMJ innervation status in mice which express the G93A SOD1 mutation. At P30, all NMJs of the fast medial gastrocnemius (MG) muscle were fully innervated by a single motor axon but 50% of NMJs lacked TSC cell bodies and were instead covered by the processes of Schwann cells with cell bodies located on the preterminal axons. NMJs in P30 slow soleus muscles were also fully innervated by single motor axons and only 5% of NMJs lacked a TSC cell body. At P60, about 25% of MG NMJs were denervated and lacked labeling for TSCs while about 60% of in...
Source: Experimental Neurology - September 25, 2015 Category: Neurology Authors: Carrasco DI, Seburn KL, Pinter MJ Tags: Exp Neurol Source Type: research

An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior.
Abstract Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8a(med) and Scn8a(med-jo) mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding posi...
Source: Experimental Neurology - September 24, 2015 Category: Neurology Authors: Makinson CD, Dutt K, Lin F, Papale LA, Shankar A, Barela AJ, Liu R, Goldin AL, Escayg A Tags: Exp Neurol Source Type: research