Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage.
This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was de...
Source: Experimental Neurology - August 29, 2018 Category: Neurology Authors: Yang X, Sun J, Kim TJ, Kim YJ, Ko SB, Kim CK, Jia X, Yoon BW Tags: Exp Neurol Source Type: research

Commentary on Giralt et al.: PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease.
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia and the 6th leading cause of death. Although research has revealed significant information about AD, much is yet to be discovered about the precise biological changes that cause AD and how the disease could be prevented, slowed, or stopped. Accumulating evidence suggests the involvement of the non-receptor proline-rich tyrosine kinase 2 (Pyk2) in AD, but the downstream signaling events triggered by this protein and their implications on the pathology of the disease were unclear until recently. A ...
Source: Experimental Neurology - August 29, 2018 Category: Neurology Authors: Polis B, Gil-Henn H Tags: Exp Neurol Source Type: research

Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs.
In this study, we carried out modifier screening of the dFIG4 knockdown-induced rough eye phenotype using a set of chromosomal deficiency lines on the second chromosome. By genetic screening, we detected 9 and 15 chromosomal regions whose deletions either suppressed or enhanced the rough eye phenotype induced by the dFIG4 knockdown. By further genetic screening with mutants of individual genes in one of these chromosomal regions, we identified the gene CR18854 that suppressed the rough eye phenotype and the loss-of-cone cell phenotype. The CR18854 gene encodes a long non-coding RNA (lncRNA) consisting of 2566 bases. Mutati...
Source: Experimental Neurology - August 27, 2018 Category: Neurology Authors: Muraoka Y, Nakamura A, Tanaka R, Suda K, Azuma Y, Kushimura Y, Piccolo LL, Yoshida H, Mizuta I, Tokuda T, Mizuno T, Nakagawa M, Yamaguchi M Tags: Exp Neurol Source Type: research

Dephosphorylated rather than hyperphosphorylated Tau triggers a pro-inflammatory profile in microglia through the p38 MAPK pathway.
ós M Abstract Tauopathies are a broad set of neurodegenerative dementias characterized by the aggregation of Tau protein. Activated microglia and elevated levels of pro-inflammatory molecules are also pathological hallmarks of tauopathies. In these diseases, intracellular Tau is secreted to the extracellular space, where it interacts with other cells, such as neurons and glia, promoting inflammation. However, the mechanism through which extracellular Tau triggers pro-inflammatory responses in microglia remains unknown. Primary microglia cultures were treated with extracellular Tau in its hyperphosphorylated...
Source: Experimental Neurology - August 20, 2018 Category: Neurology Authors: Perea JR, Ávila J, Bolós M Tags: Exp Neurol Source Type: research

Protective effects of Withania somnifera extract in SOD1G93A mouse model of amyotrophic lateral sclerosis.
Abstract Withania somnifera (WS; commonly known as Ashwagandha or Indian ginseng) is a medicinal plant whose extracts have been in use for centuries in various regions of the world as a rejuvenator. There is now a growing body of evidence documenting neuroprotective functions of the plant extracts or its purified compounds in several models of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Based on the extract's beneficial effect in a mouse model of ALS with TDP-43 proteinopathy, the current study was designed to test its efficacy in another model of familial ALS. Our results show that a...
Source: Experimental Neurology - August 19, 2018 Category: Neurology Authors: Dutta K, Patel P, Julien JP Tags: Exp Neurol Source Type: research

Bromodomain and extraterminal domain-containing protein inhibition attenuates acute inflammation after spinal cord injury.
In this study, we investigated the role of BETs in promoting inflammation in neural cells and the ability of the BET inhibitor JQ1 to decrease inflammation acutely after SCI. Expression of BET mRNA was assessed via qPCR in purified primary mouse macrophages, astrocytes, neurons, oligodendrocytes, and microglia, as well as in naïve, sham-injured, and contusion-injured mouse spinal cord. Brd2, Brd3, and Brd4 mRNA were expressed in all purified primary neural cells and in the uninjured and injured mouse spinal cord. BET inhibition significantly attenuated proinflammatory signaling in all activated cell populations in vit...
Source: Experimental Neurology - August 19, 2018 Category: Neurology Authors: Rudman MD, Choi JS, Lee HE, Tan SK, Ayad NG, Lee JK Tags: Exp Neurol Source Type: research

Muscle-dominant wild-type TDP-43 expression induces myopathological changes featuring tubular aggregates and TDP-43-positive inclusions.
Abstract Muscle histology of sporadic inclusion body myositis (sIBM) demonstrates inflammatory findings and degenerative features including accumulation of TAR DNA-binding protein of 43 kDa (TDP-43). However, whether sarcoplasmic accumulation of TDP-43 is a primary trigger of muscle degeneration or a secondary event resulting from muscle degeneration in the pathophysiology of sIBM remained unclear. Our study aimed to discover whether muscle-dominant expression of TDP-43 is a primary cause of muscle degeneration. We generated several lines of wild-type TDP-43 transgenic mice driven by a creatine kinase 8 promoter...
Source: Experimental Neurology - August 18, 2018 Category: Neurology Authors: Tawara N, Yamashita S, Kawakami K, Kurashige T, Zhang Z, Tasaki M, Yamamoto Y, Nishikami T, Doki T, Zhang X, Matsuo Y, Kimura E, Tawara A, Maeda Y, Hauschka SD, Maruyama H, Ando Y Tags: Exp Neurol Source Type: research

Recovery after spinal cord injury by modulation of the proteoglycan receptor PTP σ.
Recovery after spinal cord injury by modulation of the proteoglycan receptor PTPσ. Exp Neurol. 2018 Aug 14;: Authors: Rink S, Arnold D, Wöhler A, Bendella H, Meyer C, Manthou M, Papamitsou T, Sarikcioglu L, Angelov DN Abstract SCI is followed by dramatic upregulation of chondroitin sulfate proteoglycans (CSPGs) which limit axonal regeneration, oligodendrocyte replacement and remyelination. The recent discovery of the specific CSPGs signaling receptor protein tyrosine phosphatase sigma (RPTPσ) provided an opportunity to refine the therapeutic approach to overcome CSPGs inhibitory actio...
Source: Experimental Neurology - August 14, 2018 Category: Neurology Authors: Rink S, Arnold D, Wöhler A, Bendella H, Meyer C, Manthou M, Papamitsou T, Sarikcioglu L, Angelov DN Tags: Exp Neurol Source Type: research

Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson's disease model.
In conclusion, the degeneration of orexinergic neurons in this model of PD can be related to impaired chemoreceptor function in the dark phase. PMID: 30110606 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 12, 2018 Category: Neurology Authors: Oliveira LM, Falquetto B, Moreira TS, Takakura AC Tags: Exp Neurol Source Type: research

High glucose concentration suppresses a SIRT2 regulated pathway that enhances neurite outgrowth in cultured adult sensory neurons.
Abstract In peripheral nerve under hyperglycemic conditions high flux of d-glucose through the polyol pathway drives an aberrant redox state contributing to neurodegeneration in diabetic sensorimotor polyneuropathy (DSPN). Sirtuins, including SIRT2, detect the redox state via the NAD+/NADH ratio to regulate mitochondrial function via, in part, AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α). In adult dorsal root ganglia (DRG) sensory neurons mitochondrial dysfunction has been proposed as an etiological factor in dying-back neuropathy i...
Source: Experimental Neurology - August 10, 2018 Category: Neurology Authors: Schartner E, Sabbir MG, Saleh A, Silva RV, Chowdhury SR, Smith DR, Fernyhough P Tags: Exp Neurol Source Type: research

Targeting histone deacetylation for recovery of maternal deprivation-induced changes in BDNF and AKAP150 expression in the VTA.
Abstract Severe early life stressors increase the probability of developing psychiatric disorders later in life through modifications in neuronal circuits controlling brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling from the ventral tegmental area (VTA) through changes at GABAergic synapses that were reversible by in vitro histone deacetylase (HDAC) inhibition which led to restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and subsequently recovered GABAergic plasticity (Authement...
Source: Experimental Neurology - August 10, 2018 Category: Neurology Authors: Shepard RD, Gouty S, Kassis H, Berenji A, Zhu W, Cox BM, Nugent FS Tags: Exp Neurol Source Type: research

Mutation of hop-1 and pink-1 attenuates vulnerability of neurotoxicity in C. elegans: the role of mitochondria-associated membrane proteins in Parkinsonism.
Abstract Mitochondrial dysfunction is considered as a critical mechanism in the pathogenesis of Parkinson's disease (PD). Increasing evidence supports the notion of mitochondria-associated membranes (MAMs) in mitochondrial dysfunction; yet little is known about the role of MAMs-related proteins in the pathogenesis of PD. Herein we exposed the nematode Caenorhabditis elegans to 0.5-10.0 μM rotenone (RO) or 0.2-1.6 mM paraquat (PQ) for 3 days. Our results showed that both RO and PQ induced similar Parkinsonism including motor deficits and dopaminergic degeneration. RO/PQ caused mitochondrial damages charact...
Source: Experimental Neurology - August 1, 2018 Category: Neurology Authors: Wu S, Lei L, Song Y, Liu M, Lu S, Lou D, Shi Y, Wang Z, He D Tags: Exp Neurol Source Type: research

Increased expression of toll-like receptor 3, an anti-viral signaling molecule, and related genes in alzheimer's disease brains.
Abstract The focus of this study is the expression of Toll-like receptor-3 (TLR-3), a receptor for double-stranded RNA, in human brains affected by Alzheimer's disease (AD) pathology. Toll-like receptors are a family of pattern recognition molecules primarily involved in host defenses to microbial pathogens, but roles in neurodegenerative disease have also been shown, as amyloid beta (Aβ) can be a ligand for TLR-2 and -4 and α-synuclein for TLR-1 and TLR-2, while TLR-9 activation promotes Aβ removal. However, involvement of TLR-3 in AD has not been rigorously studied. Immunohistochemical analyses i...
Source: Experimental Neurology - August 1, 2018 Category: Neurology Authors: Walker DG, Tang TM, Lue LF Tags: Exp Neurol Source Type: research

Therapeutic efficacy of regulable GDNF expression for Huntington's and Parkinson's disease by a high-induction, background-free "GeneSwitch" vector.
Therapeutic efficacy of regulable GDNF expression for Huntington's and Parkinson's disease by a high-induction, background-free "GeneSwitch" vector. Exp Neurol. 2018 Aug 01;: Authors: Cheng S, Tereshchenko J, Zimmer V, Vachey G, Pythoud C, Rey M, Liefhebber J, Raina A, Streit F, Mazur A, Bähr M, Konstantinova P, Déglon N, Kügler S Abstract Gene therapy is currently an irreversible approach, without possibilities to fine-tune or halt the expression of a therapeutic gene product. Especially when expressing neurotrophic factors to treat neurodegenerative disorders, options to r...
Source: Experimental Neurology - August 1, 2018 Category: Neurology Authors: Cheng S, Tereshchenko J, Zimmer V, Vachey G, Pythoud C, Rey M, Liefhebber J, Raina A, Streit F, Mazur A, Bähr M, Konstantinova P, Déglon N, Kügler S Tags: Exp Neurol Source Type: research

Evidence of axon connectivity across a spinal cord transection in rats treated with epidural stimulation and motor training combined with olfactory ensheathing cell transplantation.
Abstract Olfactory ensheathing cells (OECs) are unique glia that support axon outgrowth in the olfactory system, and when used as cellular therapy after spinal cord injury, improve recovery and axon regeneration. Here we assessed the effects of combining OEC transplantation with another promising therapy, epidural electrical stimulation during a rehabilitative motor task. Sprague-Dawley rats received a mid-thoracic transection and transplantation of OECs or fibroblasts (FBs) followed by lumbar stimulation while climbing an inclined grid. We injected pseudorabies virus (PRV) into hindlimb muscles 7 months post-in...
Source: Experimental Neurology - July 26, 2018 Category: Neurology Authors: Thornton MA, Mehta MD, Morad TT, Ingraham KL, Khankan RR, Griffis KG, Yeung AK, Zhong H, Roy RR, Reggie Edgerton V, Phelps PE Tags: Exp Neurol Source Type: research

A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke.
Abstract Stroke is a leading cause of disability and death world-wide and nutrition is a modifiable risk factor for stroke. Metheylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of folic acid, a B-vitamin. In humans, a polymorphism in MTHFR (677C→T) is linked to increased risk of stroke, but the mechanisms remain unknown. The Mthfr+/- mice mimic a phenotype described in humans at bp677. Using this mouse model, the aim of this study was to investigate the impact of MTHFR deficiency on stroke outcome. Male Mthfr+/- and wildtype littermate control mice were aged (~1.5-year-old) and...
Source: Experimental Neurology - July 25, 2018 Category: Neurology Authors: Jadavji NM, Emmerson JT, Shanmugalingam U, MacFarlane AJ, Willmore WG, Smith PD Tags: Exp Neurol Source Type: research

Oligodendrocytic but not neuronal Nogo restricts corticospinal axon sprouting after CNS injury.
Abstract Recovery from injury to the central nervous system (CNS) is limited in the mammalian adult. Nonetheless, some degree of spontaneous recovery occurs after partial CNS injury. Compensatory axonal growth from uninjured neurons, termed sprouting, contributes to this naturally occurring recovery process and can be modulated by molecular intervention. Extensive studies have depicted a long-held hypothesis that oligodendrocyte-derived Nogo restricts axonal sprouting and functional recovery after CNS injury. However, cell type-specific function of Nogo in compensatory sprouting, spinal axon repair or functional r...
Source: Experimental Neurology - July 25, 2018 Category: Neurology Authors: Meves JM, Geoffroy CG, Kim ND, Kim JJ, Zheng B Tags: Exp Neurol Source Type: research

The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition.
Abstract The G2019S mutation in LRRK2 is one of the most common known genetic causes of neurodegeneration and Parkinson disease (PD). LRRK2 mutations are thought to enhance LRRK2 kinase activity. Efficacious small molecule LRRK2 kinase inhibitors with favorable drug properties have recently been developed for pre-clinical studies in rodent models, and inhibitors have advanced to safety trials in humans. Rats that express human G2019S-LRRK2 protein and G2019S-LRRK2 knock-in mice provide newly characterized models to better understand the ostensible target for inhibitors. Herein, we explore the relationships between...
Source: Experimental Neurology - July 23, 2018 Category: Neurology Authors: Kelly K, Wang S, Boddu R, Liu Z, Moukha-Chafiq O, Augelli-Szafran C, West AB Tags: Exp Neurol Source Type: research

Impairment of frequency-specific responses associated with altered electrical activity patterns in auditory thalamus following focal and general demyelination.
HC Abstract Multiple sclerosis is characterized by intermingled episodes of de- and remyelination and the occurrence of white- and grey-matter damage. To mimic the randomly distributed pathophysiological brain lesions observed in MS, we assessed the impact of focal white and grey matter demyelination on thalamic function by directing targeted lysolecithin-induced lesions to the capsula interna (CI), the auditory cortex (A1), or the ventral medial geniculate nucleus (vMGN) in mice. Pathophysiological consequences were compared with those of cuprizone treatment at different stages of demyelination and remyelination...
Source: Experimental Neurology - July 23, 2018 Category: Neurology Authors: Narayanan V, Cerina M, Göbel K, Meuth P, Herrmann AM, Fernandez-Orth J, Stangel M, Gudi V, Skripuletz T, Daldrup T, Lesting J, Schiffler P, Wiendl H, Seidenbecher T, Meuth SG, Budde T, Pape HC Tags: Exp Neurol Source Type: research

Wip1 knockout inhibits neurogenesis by affecting the Wnt/ β-catenin signaling pathway in focal cerebral ischemia in mice.
Wip1 knockout inhibits neurogenesis by affecting the Wnt/β-catenin signaling pathway in focal cerebral ischemia in mice. Exp Neurol. 2018 Jul 23;: Authors: Qiu CW, Liu ZY, Hou K, Liu SY, Hu YX, Zhang L, Zhang FL, Lv KY, Kang Q, Hu WY, Ma N, Jiao Y, Bai WJ, Xiao ZC Abstract Neurogenesis correlates closely with the recovery of neural function after brain ischemia but the critical proteins and signaling pathways involved remain unclear. The phosphatase WIP1 has been shown to regulate neurogenesis in models of aging. However, it is not known if WIP1 affects neurogenesis and functional recovery after ...
Source: Experimental Neurology - July 23, 2018 Category: Neurology Authors: Qiu CW, Liu ZY, Hou K, Liu SY, Hu YX, Zhang L, Zhang FL, Lv KY, Kang Q, Hu WY, Ma N, Jiao Y, Bai WJ, Xiao ZC Tags: Exp Neurol Source Type: research

Glia-neuron energy metabolism in health and diseases: New insights into the role of nervous system metabolic transporters.
This article reviews the current understanding of the long existing controversies regarding energy substrate and utilization in the nervous system and discusses the role of metabolic transporters in health and diseases of the nervous system. PMID: 30044944 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 22, 2018 Category: Neurology Authors: Jha MK, Morrison BM Tags: Exp Neurol Source Type: research

Defective daily temperature regulation in a mouse model of amyotrophic lateral sclerosis.
Abstract Current understanding of the pathogenesis of the familial form of amyotrophic lateral sclerosis has been aided by the study of transgenic mice that over-express mutated forms of the human CuZn-superoxide dismutase (SOD1) gene. While mutant SOD1 in motor neurons determines disease onset, other non-cell autonomous factors are critical for disease progression, and altered energy metabolism has been implicated as a contributing factor. Since most energy expended by laboratory mice is utilized to defend body temperature (Tb), we analyzed thermoregulation in transgenic mice carrying the G93A mutation of the hum...
Source: Experimental Neurology - July 18, 2018 Category: Neurology Authors: Braun MC, Castillo-Ruiz A, Indic P, Jung DY, Kim JK, Brown RH, Swoap SJ, Schwartz WJ Tags: Exp Neurol Source Type: research

Inhibiting Jumoji domain containing protein 3 (JMJD3) prevent neuronal apoptosis from stroke.
Abstract Control of p53 by histone methylation is closely related in the neuronal apoptosis following ischemic stroke. In mammalian cells, demethylation of methylated lysine residue of histones is catalyzed by Jumonji domain-containing proteins (JMJD) family. Among them, JMJD3 is reported to be a hypoxic target gene and expressed in all cell types of brain including neurons. However, the role of JMJD3 on process of neuronal apoptosis after ischemic stroke is still largely unknown. PCR, immunostaining and Western blotting results indicated that JMJD3 expression was upregulated in cultured neurons upon oxygen-glucos...
Source: Experimental Neurology - July 17, 2018 Category: Neurology Authors: Zhang H, Wang J, Huang J, Shi T, Ma X, Luo X, Li X, Li M Tags: Exp Neurol Source Type: research

Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development against hypoxia-ischemia.
This study examined the neuroprotective effects of allogeneic MSC, derived from preterm umbilical cord blood (UCB), in a preterm sheep model of white matter injury. METHODS: Quad-lineage differentiation, clonogenicity and self-renewal ability of UCB-derived MSC were confirmed. Chronically instrumented fetal sheep (0.7 gestation) received either 25 min hypoxia-ischemia (HI) to induce preterm brain injury, or sham-HI. Ten million MSC, or saline, were administered iv to fetuses at 12 h after HI. Fetal brains were collected 10d after HI for histopathology and immunocytochemistry. RESULTS: HI induced white matter ...
Source: Experimental Neurology - July 13, 2018 Category: Neurology Authors: Li J, Yawno T, Sutherland AE, Gurung S, Paton M, McDonald C, Tiwari A, Pham Y, Castillo-Melendez M, Jenkin G, Miller SL Tags: Exp Neurol Source Type: research

Sigma-1 receptor activation alleviates blood-brain barrier dysfunction in vascular dementia mice.
Abstract Sigma-1 receptor (Sig-1R) activation has been shown to decrease infarct volume and enhance neuronal survival after brain ischemia-reperfusion (IR) in rodent models. The present study aims to investigate first the effect of Sig-1R activation on blood-brain barrier (BBB) disruption during experimental stroke. Male C57BL/6 mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 15 min, and the worst BBB leakage was observed on the 7th day after brain IR. To confirm the BBB protective role of Sig-1R, mice were divided into five groups (sham group, BCCAO group, PRE084 group, BD1047 group...
Source: Experimental Neurology - July 10, 2018 Category: Neurology Authors: Liu DY, Chi TY, Ji XF, Liu P, Qi XX, Zhu L, Wang ZQ, Lin-Li, Chen L, Zou LB Tags: Exp Neurol Source Type: research

Alternative RNA splicing associated with axon regeneration after rat peripheral nerve injury.
Abstract The intrinsic axon regeneration capacity is crucial for peripheral nerve regeneration after injury. Identifying key molecules involved in this process makes great contribution to the investigation of peripheral nerve injury repair. Alternative splicing (AS) is an important regulation mode of eukaryotic gene expression, which has been widely studied both in physiological and pathological processes. However, less is known about the role of AS in peripheral nerve regeneration. In this work, to identify the AS events associated with axon regeneration capacity, we analyzed the AS events during sciatic nerve in...
Source: Experimental Neurology - July 4, 2018 Category: Neurology Authors: Mao S, Zhang S, Zhou Z, Shi X, Huang T, Feng W, Yao C, Gu X, Yu B Tags: Exp Neurol Source Type: research

MANF protects dopamine neurons and locomotion defects from a human α-synuclein induced Parkinson's disease model in C. elegans by regulating ER stress and autophagy pathways.
MANF protects dopamine neurons and locomotion defects from a human α-synuclein induced Parkinson's disease model in C. elegans by regulating ER stress and autophagy pathways. Exp Neurol. 2018 Jun 27;: Authors: Zhang Z, Shen Y, Luo H, Zhang F, Jing L, Wu Y, Xia X, Song Y, Li W, Jin L Abstract There are many studies have demonstrated that mesencephalic astrocyte-derived neurotrophic factor (MANF) has been shown protective effects on neurotoxin based models of Parkinson's disease (PD). It still remains unclear whether MANF can rescue dopaminergic (DA) neurons in an α-synuclein model. Glial ce...
Source: Experimental Neurology - June 27, 2018 Category: Neurology Authors: Zhang Z, Shen Y, Luo H, Zhang F, Jing L, Wu Y, Xia X, Song Y, Li W, Jin L Tags: Exp Neurol Source Type: research

Disruption of the Zdhhc9 intellectual disability gene leads to behavioural abnormalities in a mouse model.
In this study, we have undertaken behavioural phenotyping, magnetic resonance imaging (MRI) and isolation of S-acylated proteins to investigate the effect of disruption of the Zdhhc9 gene in mice in a C57BL/6 genetic background. Zdhhc9 mutant male mice exhibit a range of abnormalities compared with their wild-type littermates: altered behaviour in the open-field test, elevated plus maze and acoustic startle test that is consistent with a reduced anxiety level; a reduced hang time in the hanging wire test that suggests underlying hypotonia but which may also be linked to reduced anxiety; deficits in the Morris water maze te...
Source: Experimental Neurology - June 23, 2018 Category: Neurology Authors: Kouskou M, Thomson DM, Brett RR, Wheeler L, Tate RJ, Pratt JA, Chamberlain LH Tags: Exp Neurol Source Type: research

Altered glutamate response and calcium dynamics in iPSC-derived striatal neurons from XDP patients.
egner F Abstract X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder endemic to Panay Island (Philippines). Patients present with generalizing dystonia and parkinsonism. Genetic changes surrounding the TAF1 (TATA-box binding protein associated factor 1) gene have been associated with XDP inducing a degeneration of striatal spiny projection neurons. There is little knowledge about the pathophysiology of this disorder. Our objective was to generate and analyze an in-vitro model of XDP based on striatal neurons differentiated from induced pluripotent stem cells (iPSC). We generated iPSC from patient ...
Source: Experimental Neurology - June 23, 2018 Category: Neurology Authors: Capetian P, Stanslowsky N, Bernhardi E, Grütz K, Domingo A, Brüggemann N, Naujock M, Seibler P, Klein C, Wegner F Tags: Exp Neurol Source Type: research

RhoA regulates Schwann cell differentiation through JNK pathway.
Abstract RhoA is a small GTPase that regulates many functions of mammalian cells via actin reorganization. Lots of studies uncovered that its activation acts as a major negative regulator of neurite extension, and inhibition of RhoA activity or reduction of its expression can promote neuron survival and axonal regeneration. However, little is known about whether RhoA also exerts important functions on Schwann cells (SCs) which are the glial cells of the peripheral nervous system (PNS). Recently, we reported that RhoA plays important roles in the proliferation, migration and myelination. In the present study, using...
Source: Experimental Neurology - June 22, 2018 Category: Neurology Authors: Wen J, Tan D, Li L, Wang X, Pan M, Guo J Tags: Exp Neurol Source Type: research

Myelinated axons fail to develop properly in a genetically authentic mouse model of Charcot-Marie-Tooth disease type 2E.
Abstract We have analyzed a mouse model of Charcot-Marie-Tooth disease 2E (CMT2E) harboring a heterozygous p.Asn98Ser (p.N98S) Nefl mutation, whose human counterpart results in a severe, early-onset neuropathy. Behavioral, electrophysiological, and pathological analyses were done on separate cohorts of NeflN98S/+ mutant mice and their wild type Nefl+/+ littermates between 8 and 48 weeks of age. The motor performance of NeflN98S/+ mice, as evidenced by altered balance and gait measures, was impaired at every age examined (from 6 to 25 weeks of age). At all times examined, myelinated axons were smaller and conta...
Source: Experimental Neurology - June 22, 2018 Category: Neurology Authors: Lancaster E, Li J, Hanania T, Liem R, Scheideler MA, Scherer SS Tags: Exp Neurol Source Type: research

Chronic traffic noise stress accelerates brain impairment and cognitive decline in mice.
Abstract Although traffic noise exposure is a well-known environmental pollutant whose negative health effect has been discussed in different aspects of the human life, only a few animal studies have tackled this issue as a cohort study, which is not feasible to be addressed in human studies. In addition to the deleterious impact of the daytime noise on well-being, chronic nocturnal noise can also disturb sleep and affects physical and mental health, but to date, little research has examined the neurobiological effects light/dark cycles of traffic noise exposure. We investigated the effects of light/dark cycles an...
Source: Experimental Neurology - June 21, 2018 Category: Neurology Authors: Jafari Z, Kolb BE, Mohajerani MH Tags: Exp Neurol Source Type: research

The human motor neuron axonal transcriptome is enriched for transcripts related to mitochondrial function and microtubule-based axonal transport.
MA Abstract Local axonal translation of specific mRNA species plays an important role in axon maintenance, plasticity during development and recovery from injury. Recently, disrupted axonal mRNA transport and translation have been linked to neurodegenerative disorders. To identify mRNA species that are actively transported to axons and play an important role in axonal physiology, we mapped the axonal transcriptome of human induced pluripotent stem cell (iPSC)-derived motor neurons using permeable inserts to obtain large amounts of enriched axonal material for RNA isolation and sequencing. Motor neurons from healt...
Source: Experimental Neurology - June 20, 2018 Category: Neurology Authors: Maciel R, Bis D, Rebelo AP, Saghira C, Züchner S, Saporta MA Tags: Exp Neurol Source Type: research

Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis.
Abstract Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterized by the systemic loss of motor neurons with prominent astrocytosis and microgliosis in the spinal cord and brain. Astrocytes play an essential role in maintaining extracellular microenvironments that surround motor neurons, and are activated by various insults. Growing evidence points to a non-cell autonomous neurotoxicity caused by chronic and sustained astrocytic activation in patients with neurodegenerative diseases, including ALS. However, the mechanisms that underlie the harmful effects of astrocytosi...
Source: Experimental Neurology - June 19, 2018 Category: Neurology Authors: Shijo T, Warita H, Suzuki N, Ikeda K, Mitsuzawa S, Akiyama T, Ono H, Nishiyama A, Izumi R, Kitajima Y, Aoki M Tags: Exp Neurol Source Type: research

Memantine rescues prenatal citalopram exposure-induced striatal and social abnormalities in mice.
Abstract Prenatal exposure to citalopram (CTM), an antidepressant drug, has been associated with altered behavior, including autism-like symptoms in both human and rodent offspring. However, the neurological basis underlying these abnormal behaviors is not well understood. Here, we examined behavioral, morphological, and biochemical alterations in the male and female offspring of C57BL/6 mouse mothers that had been exposed to CTM during the last trimester of gestation. We observed abnormal behavior such as anxiety, altered locomotion and disordered social interactions in 2-5 month old offspring with prenatal CTM...
Source: Experimental Neurology - June 15, 2018 Category: Neurology Authors: Zahra A, Jiang J, Chen Y, Long C, Yang L Tags: Exp Neurol Source Type: research

Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits.
In this report, we show that intravenous (IV) CDC-EVs (0.75 mg/kg) administered 1-hour post-embolization significantly attenuate behavioral deficits following an embolic stroke in rabbits. In CDC-EV-treated rabbits, P50 (3.63 ± 1.27 mg, n = 24) was increased by 245% over vehicle control (1.05 ± 0.15 mg, n = 24); by comparison, rt-PA increased P50 by 91% (2.01 ± 0.24 mg, n = 23). Importantly, the therapy was also without adverse effects on intracerebral hemorrhage or survival rate of embolized rabbits. Thus, as a first step toward widespread use, CDC-EVs, given adjunctive...
Source: Experimental Neurology - June 13, 2018 Category: Neurology Authors: Lapchak PA, Boitano PD, de Couto G, Marbán E Tags: Exp Neurol Source Type: research

Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy.
The objective of this study is to test the feasibility of using serum neurofilament light chain (NfL) as a disease biomarker in Chemotherapy Induced Peripheral Neuropathy (CIPN) since this easy accessible biological test may have a large impact on clinical management and safety of cancer patients. We performed this preclinical study using a well-characterized rat model based on repeated administration of the cytostatic drug vincristine (VCR, 0.2 mg/kg intravenously via the tail vein once/week for 4 times). Serial NfL serum concentration measured using the in-house Simoa NfL assay and peripheral neuropathy onset was measu...
Source: Experimental Neurology - June 13, 2018 Category: Neurology Authors: Meregalli C, Fumagalli G, Alberti P, Canta A, Carozzi VA, Chiorazzi A, Monza L, Pozzi E, Sandelius Å, Blennow K, Zetterberg H, Marmiroli P, Cavaletti G Tags: Exp Neurol Source Type: research

The accumulation of enzymatically inactive cuproenzymes is a CNS-specific phenomenon of the SOD1G37R mouse model of ALS and can be restored by overexpressing the human copper transporter hCTR1.
In this study, we demonstrate that cuproenzyme dysfunction extends beyond SOD1 in SOD1G37R mice to also affect the endogenous copper-dependent ferroxidase ceruloplasmin. We show that SOD1 and ceruloplasmin both accumulate progressively in the SOD1G37R mouse spinal cord as the animals' ALS-like symptoms progress, yet the biochemical activity of the two cuproenzymes does not increase commensurately, indicating that, as per mutant SOD1, ceruloplasmin accumulates in a copper-deficient form. Consistent with this finding, we show that expression of the human copper transporter 1 (hCTR1) in SOD1G37R mice increases copper levels i...
Source: Experimental Neurology - June 12, 2018 Category: Neurology Authors: Hilton JB, Kysenius K, White AR, Crouch PJ Tags: Exp Neurol Source Type: research

Anticonvulsant agent DPP4 inhibitor sitagliptin downregulates CXCR3/RAGE pathway on seizure models.
In this study, we determined that sitagliptin remarkably attenuated the severity of seizures in a pentylenetetrazole (PTZ)-induced rat model. In addition, sitagliptin decreased epileptiform activity measured by electroencephalography (EEG) recordings and patch-clamp methods. Interestingly, sitagliptin pretreatment downregulated the RAGE-JAK2/STAT3 pathway and decreased the expression of CXCL4 and CXCR3. Moreover, CXCR3 knockdown decreased the expression of RAGE, JAK2 and STAT3 in cultured neurons, which suggests that CXCR3 is upstream of the RAGE-JAK2/STAT3 pathway. Altogether, our present data suggest that sitagliptin has...
Source: Experimental Neurology - June 6, 2018 Category: Neurology Authors: Liu Y, Hou B, Zhang Y, Fan Y, Peng B, Liu W, Han S, Yin J, He X Tags: Exp Neurol Source Type: research

Neurotrophin-3 provides neuroprotection via TrkC receptor dependent pErk5 activation in a rat surgical brain injury model.
CONCLUSIONS: Topical application of NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. The protective effect of NT-3 was possibly mediated via TrkC dependent activation of Erk5. PMID: 29883578 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 5, 2018 Category: Neurology Authors: Akyol O, Sherchan P, Yilmaz G, Reis C, Ho WM, Wang Y, Huang L, Solaroglu I, Zhang JH Tags: Exp Neurol Source Type: research

Endothelial colony-forming cell-derived exosomes restore blood-brain barrier continuity in mice subjected to traumatic brain injury.
Abstract Traumatic brain injury (TBI) tends to cause disruption of the blood-brain barrier (BBB). Previous studies have shown that intravenously or intracerebroventricularly infused human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) can home to injury sites and improve outcomes in mice subjected to experimental TBI. Several reports have demonstrated that these cells did not incorporate directly into newly formed vasculature but instead stimulated the proliferation and migration of tissue-resident endothelial cells (ECs) via paracrine mechanisms. In the present study, exosomes, which range ...
Source: Experimental Neurology - June 5, 2018 Category: Neurology Authors: Gao W, Li F, Liu L, Xu X, Zhang B, Wu Y, Yin D, Zhou S, Sun D, Huang Y, Zhang J Tags: Exp Neurol Source Type: research

Stress modulates cortical excitability via α-2 adrenergic and glucocorticoid receptors: As assessed by spreading depression.
Stress modulates cortical excitability via α-2 adrenergic and glucocorticoid receptors: As assessed by spreading depression. Exp Neurol. 2018 May 29;: Authors: Yapıcı-Eser H, Dönmez-Demir B, Kılıç K, Eren-Koçak E, Dalkara T Abstract An increase in cortical excitability may be one of the factors mediating stress-induced vulnerability to neuropsychiatric disorders. Since stress increases extracellular glutamate and predisposes to migraine with aura attacks, we aimed to study the effect of stress on cortical spreading depression (CSD), the biological substrate of migraine aur...
Source: Experimental Neurology - May 29, 2018 Category: Neurology Authors: Yapıcı-Eser H, Dönmez-Demir B, Kılıç K, Eren-Koçak E, Dalkara T Tags: Exp Neurol Source Type: research

Ezetimibe, a NPC1L1 inhibitor, attenuates neuronal apoptosis through AMPK dependent autophagy activation after MCAO in rats.
In this study, we explored whether Eze could attenuate neuronal apoptosis in the rat model of middle cerebral artery occlusion (MCAO), specifically via activation of the AMPK/ULK1/autophagy pathway. Two hundred and one male Sprague-Dawley rats were subjected to transient MCAO followed by reperfusion. Eze was administered 1 h after MCAO. To elucidate the underlying molecular mechanism, Dorsomorphin, a selective AMPK inhibitor, and 3-methyladenine (3-MA), an autophagy inhibitor, were injected intracerebroventricularly before MCAO. Infarct volume, neurological score, brain cholesterol levels, immunofluorescence staining, We...
Source: Experimental Neurology - May 28, 2018 Category: Neurology Authors: Yu J, Li X, Matei N, McBride D, Tang J, Yan M, Zhang JH Tags: Exp Neurol Source Type: research

Spatial distribution affects the role of CSPGs in nerve regeneration via the actin filament-mediated pathway.
Abstract CSPGs are components of the extracellular matrix in the nervous system, where they serve as cues for axon guidance during development. After a peripheral nerve injury, CSPGs switch roles and become axon inhibitors and become diffusely distributed at the injury site. To investigate whether the spatial distribution of CSPGs affects their role, we combined in vitro DRG cultures with CSPG stripe or coverage assays to simulate the effect of a patterned substrate or dispersive distribution of CSPGs on growing neurites. We observed neurite steering at linear CSPG interfaces and neurite inhibition when diffused C...
Source: Experimental Neurology - May 28, 2018 Category: Neurology Authors: Zou JL, Sun JH, Qiu S, Chen SH, He FL, Li JC, Mao HQ, Liu XL, Quan DP, Zeng YS, Zhu QT Tags: Exp Neurol Source Type: research

Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery.
Abstract Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by progressive neuronal demyelination and degeneration. Much of this damage can be attributed to microglia, the resident innate immune cells of the CNS, as well as monocyte-derived macrophages, which breach the blood-brain barrier in this inflammatory state. Upon activation, both microglia and macrophages release a variety of factors that greatly contribute to disease progression, and thus therapeutic approaches in MS focus on diminishing their activity. We use the CSF1R inhibitor PLX5622, administere...
Source: Experimental Neurology - May 24, 2018 Category: Neurology Authors: Nissen JC, Thompson KK, West BL, Tsirka SE Tags: Exp Neurol Source Type: research

PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease.
gon J, Girault JA Abstract Pyk2 is a Ca2+-activated non-receptor tyrosine kinase enriched in forebrain neurons and involved in synaptic regulation. Human genetic studies associated PTK2B, the gene coding Pyk2, with risk for Alzheimer's disease (AD). We previously showed that Pyk2 is important for hippocampal function, plasticity, and spine structure. However, its potential role in AD is unknown. To address this question we used human brain samples and 5XFAD mice, an amyloid mouse model of AD expressing mutated human amyloid precursor protein and presenilin1. In the hippocampus of 5XFAD mice and in human AD patient...
Source: Experimental Neurology - May 24, 2018 Category: Neurology Authors: Giralt A, de Pins B, Cifuentes-Díaz C, López-Molina L, Farah AT, Tible M, Deramecourt V, Arold S, Ginés S, Hugon J, Girault JA Tags: Exp Neurol Source Type: research

Subthalamic nucleus deep brain stimulation protects neurons by activating autophagy via PP2A inactivation in a rat model of Parkinson's disease.
Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum. PD rats were subjected to DBS of the STN (STN-DBS) and the effects on ...
Source: Experimental Neurology - May 21, 2018 Category: Neurology Authors: Du TT, Chen YC, Lu YQ, Meng FG, Yang H, Zhang JG Tags: Exp Neurol Source Type: research

Are dopamine receptor and transporter changes in Rett syndrome reflected in Mecp2-deficient mice?
idu S Abstract In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D...
Source: Experimental Neurology - May 18, 2018 Category: Neurology Authors: Wong DF, Blue ME, Brašić JR, Nandi A, Valentine H, Stansfield KH, Rousset O, Bibat G, Yablonski ME, Johnston MV, Gjedde A, Naidu S Tags: Exp Neurol Source Type: research

Hypoxic postconditioning enhances functional recovery following endothelin-1 induced middle cerebral artery occlusion in conscious rats.
Abstract Stroke is a leading cause of death and a major contributor to neurological disability in adults. Tissue plasminogen activator is the only approved treatment. However, due to its narrow therapeutic window,
Source: Experimental Neurology - May 17, 2018 Category: Neurology Authors: Nguyen HL, Ruhoff AM, Fath T, Jones NM Tags: Exp Neurol Source Type: research

Gender difference in the effect of progesterone on neonatal hypoxic/ischemic brain injury in mouse.
This study was to investigate the effects of progesterone (PROG) on neonatal hypoxic/ischemic (NHI) brain injury, the differences in effects between genders, and the underlying mechanisms. NHI brain injury was established in both male and female neonatal mice induced by occlusion of the left common carotid artery followed by hypoxia. The mice were treated with PROG or vehicle. Fluoro-Jade B staining (F-JB), long term behavior testing, and brain magnetic resonance image (MRI) were applied to evaluate neuronal death, neurological function, and brain damage. The underlying molecular mechanisms were also investigated by Wester...
Source: Experimental Neurology - May 14, 2018 Category: Neurology Authors: Dong S, Zhang Q, Kong D, Zhou C, Zhou J, Han J, Zhou Y, Jin G, Hua X, Wang J, Hua F Tags: Exp Neurol Source Type: research