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

The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression.
CONCLUSION: MFB DBS in the FSL animals selectively affected certain types of behaviors. Exploration and vocalization remained unaltered, but cognitive performance such as speed and precision of memory recall improved compared to unstimulated and stimulated controls. Future studies should focus on the mechanisms of action of MFB DBS, and in particular on the role of dopamine in the stimulation-dependent phenotype changes. PMID: 29428214 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: Thiele S, Furlanetti L, Pfeiffer LM, Coenen VA, Döbrössy MD Tags: Exp Neurol Source Type: research

Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats.
Abstract Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood. In the present study, we examined the theory that PKC activatio...
Source: Experimental Neurology - February 8, 2018 Category: Neurology Authors: An K, Rong H, Ni H, Zhu C, Xu L, Liu Q, Chen Y, Zheng Y, Huang B, Yao M Tags: Exp Neurol Source Type: research

Sox9 knockout mice have improved recovery following stroke.
Abstract The partial recovery that can occur after a stroke has been attributed to structural and functional plasticity that compensate for damage and lost functions. This plasticity is thought to be limited in part by the presence of growth inhibitors in the central nervous system. Blocking or reducing signals from inhibitors of axonal sprouting such as Nogo and chondroitin sulfate proteoglycans (CSPGs) increases post-stroke axonal sprouting and improves recovery. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and demonstrated that conditional Sox9 ablation leads t...
Source: Experimental Neurology - February 6, 2018 Category: Neurology Authors: Xu X, Bass B, McKillop WM, Mailloux J, Liu T, Geremia NM, Hryciw T, Brown A Tags: Exp Neurol Source Type: research

Secreted amyloid precursor protein alpha activates neuronal insulin receptors and prevents diabetes-induced encephalopathy.
In this study, in vitro analysis of cortical neuronal cultures revealed that exogenous sAPPα increased IR phosphorylation in the absence of insulin. Furthermore, in an APP overexpressing mouse model, sAPPα bound IRs in the cortex with significantly greater binding in hypoinsulinemic animals. To further examine the effects of sAPPα on the diabetic brain, we next rendered sAPPα overexpressing mice insulin depleted and found that sAPPα blocked aberrant tau phosphorylation (T231) in cortical tissue after 16 weeks diabetes. sAPPα overexpression also prevented hyperphosphorylation of AKT/GSK...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Aulston BD, Shapansky J, Huang Y, Odero GL, Glazner GW Tags: Exp Neurol Source Type: research

Neuronal-specific impairment of heparan sulfate degradation in Drosophila reveals pathogenic mechanisms for Mucopolysaccharidosis type IIIA.
Abstract Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder resulting from the deficit of the N-sulfoglucosamine sulfohydrolase (SGSH) enzyme that leads to accumulation of partially-degraded heparan sulfate. MPS IIIA is characterized by severe neurological symptoms, clinically presenting as Sanfilippo syndrome, for which no effective therapy is available. The lysosomal SGSH enzyme is conserved in Drosophila and we have identified increased levels of heparan sulfate in flies with ubiquitous knockdown of SGSH/CG14291. Using neuronal specific knockdown of SGSH/CG14291 we have also observed a h...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Webber DL, Choo A, Hewson LJ, Trim PJ, Snel MF, Hopwood JJ, Richards RI, Hemsley KM, O'Keefe LV Tags: Exp Neurol Source Type: research

Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats.
In this study, we investigated the effects of epothilone D (Epo D), an analog of Epo B with a possible greater therapeutic index, on fibrotic scarring, axonal sprouting and functional recovery after SCI. Delayed systemic administration of Epo D after a moderate contusion injury (150 kDyn) in female Fischer 344 rats resulted in a reduced number of footfalls when crossing a horizontal ladder at 4 and 8 weeks post-injury. Hindlimb motor function assessed with the BBB open field locomotor rating scale and Catwalk gait analysis were not significantly altered. Moreover, formation of laminin positive fibrotic scar tissue and ...
Source: Experimental Neurology - February 1, 2018 Category: Neurology Authors: Sandner B, Puttagunta R, Motsch M, Bradke F, Ruschel J, Blesch A, Weidner N Tags: Exp Neurol Source Type: research

Dissipation of transmembrane potassium gradient is the main cause of cerebral ischemia-induced depolarization in astrocytes and neurons.
Abstract Membrane potential (VM) depolarization occurs immediately following cerebral ischemia and is devastating for the astrocyte homeostasis and neuronal signaling. Previously, an excessive release of extracellular K+ and glutamate has been shown to underlie an ischemia-induced VM depolarization. Ischemic insults should impair membrane ion channels and disrupt the physiological ion gradients. However, their respective contribution to ischemia-induced neuronal and glial depolarization and loss of neuronal excitability are unanswered questions. A short-term oxygen-glucose deprivation (OGD) was used for the purpos...
Source: Experimental Neurology - January 30, 2018 Category: Neurology Authors: Du Y, Wang W, Lutton AD, Kiyoshi CM, Ma B, Taylor AT, Olesik JW, McTigue DM, Askwith CC, Zhou M Tags: Exp Neurol Source Type: research

TREM2 overexpression attenuates neuroinflammation and protects dopaminergic neurons in experimental models of Parkinson's disease.
Abstract Triggering receptor expressed on myeloid cells-2 (TREM2) was a newly identified receptor expressed on microglia. Several observations support the hypothesis that TREM2 variation may confer susceptibility to Parkinson's disease (PD). Therefore, in this paper, we explored the role of TREM2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results revealed that overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo. Further mechanistic study revealed that TREM2 inhibited neuroinflammatio...
Source: Experimental Neurology - January 27, 2018 Category: Neurology Authors: Ren M, Guo Y, Wei X, Yan S, Qin Y, Zhang X, Jiang F, Lou H Tags: Exp Neurol Source Type: research

Diverse functions of protein tyrosine phosphatase σ in the nervous and immune systems.
Diverse functions of protein tyrosine phosphatase σ in the nervous and immune systems. Exp Neurol. 2018 Jan 25;: Authors: Ohtake Y, Saito A, Li S Abstract Tyrosine phosphorylation is a common means of regulating protein functions and signal transduction in multiple cells. Protein tyrosine phosphatases (PTPs) are a large family of signaling enzymes that remove phosphate groups from tyrosine residues of target proteins and change their functions. Among them, receptor-type PTPs (RPTPs) exhibit a distinct spatial pattern of expression and play essential roles in regulating neurite outgrowth, axon gu...
Source: Experimental Neurology - January 25, 2018 Category: Neurology Authors: Ohtake Y, Saito A, Li S Tags: Exp Neurol Source Type: research

Zn2+-induced disruption of neuronal mitochondrial function: Synergism with Ca2+, critical dependence upon cytosolic Zn2+ buffering, and contributions to neuronal injury.
Abstract Excitotoxic Zn2+ and Ca2+ accumulation contributes to neuronal injury after ischemia or prolonged seizures. Synaptically released Zn2+ can enter postsynaptic neurons via routes including voltage sensitive Ca2+ channels (VSCC), and, more rapidly, through Ca2+ permeable AMPA channels. There are also intracellular Zn2+ binding proteins which can either buffer neuronal Zn2+ influx or release bound Zn2+ into the cytosol during pathologic conditions. Studies in culture highlight mitochondria as possible targets of Zn2+; cytosolic Zn2+ can enter mitochondria and induce effects including loss of mitochondrial mem...
Source: Experimental Neurology - January 17, 2018 Category: Neurology Authors: Ji SG, Weiss JH Tags: Exp Neurol Source Type: research

Interaction of DCF1 with ATP1B1 induces impairment in astrocyte structural plasticity via the P38 signaling pathway.
Abstract Astrocytes are known to regulate and support neuronal and synaptic functions. Changes in their size and morphology in mouse models result in mental retardation. However, the mechanism underlying these morphological changes remains unclear. In the present study, abnormal astrocyte morphology was found in the mouse brain following knockout of dendritic cell factor 1 (Dcf1). Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an interaction between these two proteins, with asparagine residue 266 of ATP1B1 ...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Wang J, Zhou F, Wang D, Li J, Lu D, Li Q, Zhou H, Li W, Wang Q, Wu Y, Xie J, Wen T Tags: Exp Neurol Source Type: research

Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists.
Abstract Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistent...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Brys I, Halje P, Scheffer-Teixeira R, Varney M, Newman-Tancredi A, Petersson P Tags: Exp Neurol Source Type: research

Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to painful neuropathy induced by bortezomib.
Abstract Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bort...
Source: Experimental Neurology - January 12, 2018 Category: Neurology Authors: Liu CC, Huang ZX, Li X, Shen KF, Liu M, Ouyang HD, Zhang SB, Ruan YT, Zhang XL, Wu SL, Xin WJ, Ma C Tags: Exp Neurol Source Type: research

The role of Hedgehog-responsive fibroblasts in facial nerve regeneration.
CONCLUSION: These findings describe a key signaling pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts that reside within the nerve respond to injury and may represent a novel therapeutic target in the context of facial nerve regeneration after transection injury. PMID: 29337143 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Bobarnac Dogaru GL, Juneja SC, Shokrani A, Hui RY, Chai Y, Pepper JP Tags: Exp Neurol Source Type: research

Early activation of Egr-1 promotes neuroinflammation and dopaminergic neurodegeneration in an experimental model of Parkinson's disease.
Abstract The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak indu...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Yu Q, Huang Q, Du X, Xu S, Li M, Ma S Tags: Exp Neurol Source Type: research

Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating G αi/Gαq-CK2 signaling in ischemic stroke.
Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gαi/Gαq-CK2 signaling in ischemic stroke. Exp Neurol. 2018 Jan 11;: Authors: Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y, Bai B Abstract Cerebral ischemia/reperfusion (I/R) injury-induced neuronal apoptosis contributes to the death and disability in patients with ischemic stroke. However, underlying mechanisms remain elusive and it lacks effective treatment. Here we reported that the expression of casein kinase 2 (CK2) was significantly reduced in brains of middle cerebral artery occlusion/reperfusion (MACO/R) model ra...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y, Bai B Tags: Exp Neurol Source Type: research

Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons.
Abstract Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood (Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5 of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's identified by tdT expression and retrograde labeling with fluorogold (FG) were significantly enlarged four months following PTEN deletion, and c...
Source: Experimental Neurology - January 11, 2018 Category: Neurology Authors: Gallent EA, Steward O Tags: Exp Neurol Source Type: research

An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites.
Abstract Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4-/- neonates in vivo compared with Nrg4+/+ littermates. Neocortical pyramidal neurons cultured from Nrg4-/- embryos had significantly shorter and l...
Source: Experimental Neurology - January 6, 2018 Category: Neurology Authors: Paramo B, Wyatt S, Davies AM Tags: Exp Neurol Source Type: research

Activation of NPY-Y2 receptors ameliorates disease pathology in the R6/2 mouse and PC12 cell models of Huntington's disease.
Abstract Huntington's disease (HD) is a monogenic inherited polyglutamine-mediated neurodegenerative disorder for which effective therapies are currently unavailable. Neuropeptide Y (NPY) has been implicated as a potential therapeutic target in several neurodegenerative diseases, including HD. However, its mechanisms of action in the context of HD pathology remain unknown. Here, we investigated the beneficial effects of Y2 receptor (Y2R) activation with NPY or Y2R selective agonist NPY13-36 in the R6/2 mouse and PC12 cell models of HD. Also, we explored the effects of selective pharmacological blockage of Y2R usin...
Source: Experimental Neurology - January 5, 2018 Category: Neurology Authors: Fatoba O, Kloster E, Reick C, Saft C, Gold R, Epplen JT, Arning L, Ellrichmann G Tags: Exp Neurol Source Type: research

Decreased glutathione levels cause overt motor neuron degeneration in hSOD1WT over-expressing mice.
Abstract Mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Several lines of evidence have shown that SOD1 mutations cause ALS through a gain of a toxic function that remains to be fully characterized. A significant share of our understanding of the mechanisms underlying the neurodegenerative process in ALS comes from the study of rodents over-expressing ALS-linked mutant hSOD1. These mutant hSOD1 models develop an ALS-like phenotype. On the other hand, hemizygous mice over-expressing w...
Source: Experimental Neurology - January 4, 2018 Category: Neurology Authors: Killoy KM, Harlan BA, Pehar M, Helke KL, Johnson JA, Vargas MR Tags: Exp Neurol Source Type: research

Neuroprotective effect of acute ethanol intoxication in TBI is associated to the hierarchical modulation of early transcriptional responses.
, Roselli F Abstract Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients. We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (-30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs). We de...
Source: Experimental Neurology - January 4, 2018 Category: Neurology Authors: Chandrasekar A, Aksan B, Heuvel FO, Förstner P, Sinske D, Rehman R, Palmer A, Ludolph A, Huber-Lang M, Böckers T, Mauceri D, Knöll B, Roselli F Tags: Exp Neurol Source Type: research

The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson's disease.
Abstract Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6-OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions. T...
Source: Experimental Neurology - January 3, 2018 Category: Neurology Authors: Lima JC, Oliveira LM, Botelho MT, Moreira TS, Takakura AC Tags: Exp Neurol Source Type: research