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Experimental Neurology

Maurine C Braun, Alexandra Castillo-Ruiz, Premananda Indic, Dae Young Jung, Jason K Kim, Robert H Brown, Steven J Swoap, William J Schwartz
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 human SOD1 gene, using implantable temperature data loggers to continuously record Tb for up to 85 days...
July 18, 2018: Experimental Neurology
Huinan Zhang, Jun Wang, Jing Huang, Tingyu Shi, Xue Ma, Xiaoxing Luo, Xia Li, Mingkai Li
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-glucose deprivation (OGD) injury...
July 17, 2018: Experimental Neurology
Jingang Li, Tamara Yawno, Amy E Sutherland, Shanti Gurung, Madison Paton, Courtney McDonald, Abhilasha Tiwari, Yen Pham, Margie Castillo-Melendez, Graham Jenkin, Suzanne L Miller
INTRODUCTION: Preterm infants are at high risk for white matter injury and subsequent neurodevelopmental impairments. Mesenchymal stem/stromal cells (MSC) have anti-inflammatory/immunomodulatory actions and are of interest for neural repair in adults and newborns. 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...
July 13, 2018: Experimental Neurology
Lorraine Siebold, Andre Obenaus, Ravi Goyal
Traumatic brain injury (TBI) is a major health concern in the United States resulting in a substantial number of hospitalizations and in a broad spectrum of symptoms and disabilities. In the clinical setting, neurological responsiveness and structural imaging are used to classify mild, moderate and severe TBI. To evaluate the complex secondary and severity-specific injury response, investigators have relied on pre-clinical rodent models. The controlled cortical impact (CCI) model in mice is a widely used to study TBI...
July 12, 2018: Experimental Neurology
Muhammad M Hossain, Blair Weig, Kenneth Reuhl, Marla Gearing, Long-Jun Wu, Jason R Richardson
Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Nav ), which may contribute to its reported neuroprotective role in preclinical models of PD...
July 12, 2018: Experimental Neurology
Dan-Yang Liu, Tian-Yan Chi, Xue-Fei Ji, Peng Liu, Xiao-Xiao Qi, Lin Zhu, Zi-Qi Wang, Lin-Li, Ling Chen, Li-Bo Zou
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, PRE084 and BD1047 group; 29-35 mice for each group), and treated with agonist PRE084 (1 mg/kg) and/or antagonist BD1047 (1 mg/kg) for 7 days intraperitoneally once a day after BCCAO...
July 10, 2018: Experimental Neurology
Todd Yecies, Shun Li, Yan Zhang, Haotian Cai, Bing Shen, Jicheng Wang, James Roppolo, William de Groat, Changfeng Tai
This study examined the mechanisms underlying pudendal and tibial neuromodulation of bladder function at the single neuron level in the spinal cord. A microelectrode was inserted into the S2 spinal cord of anesthetized cats to record single neuron activity induced by bladder distention over a range of constant intravesical pressures (10-40 cmH2 O). Pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) was applied at 5 Hz frequency and 0.2 ms pulse width and at multiples of the threshold (T) intensities for inducing anal or toe twitches...
July 7, 2018: Experimental Neurology
Susu Mao, Shanshan Zhang, Zhenyu Zhou, Xiangxiang Shi, Tao Huang, Wei Feng, Chun Yao, Xiaosong Gu, Bin Yu
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 injury repair by RNA sequencing (RNA-Seq) and replicate multivariate analysis of transcript splicing (rMATS)...
July 4, 2018: Experimental Neurology
Amber R Hackett, Stephanie L Yahn, Kirill Lyapichev, Angela Dajnoki, Do-Hun Lee, Mario Rodriguez, Natasha Cammer, Ji Pak, Saloni T Mehta, Olaf Bodamer, Vance P Lemmon, Jae K Lee
The glial scar is comprised of a heterogeneous population of reactive astrocytes. NG2 glial cells (also known as oligodendrocyte progenitor cells or polydendrocytes) may contribute to this heterogeneity by differentiating into astrocytes in the injured CNS, but there have been conflicting reports about whether astrocytes comprise a significant portion of the NG2 cell lineage. By using genetic fate mapping after spinal cord injury (SCI) and experimental autoimmune encephalomyelitis (EAE) in mice, the goal of this study was to confirm and extend upon previous findings, which have shown that NG2 cell plasticity varies across CNS injuries...
July 3, 2018: Experimental Neurology
Zhuoyu Zhang, Yijue Shen, Hang Luo, Fen Zhang, Li Jing, Yuanyuan Wu, Xiaofei Xia, Yunping Song, Wei Li, Lingjing Jin
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 cell line-derived neurotrophic factor (GDNF) and its related neurturin (NRTN) can protect DA neurons in the neurotoxin but not α-synuclein animal models of PD, it failed in the clinical trials. Since α-synuclein model can better mimic the progression of human PD, in our study we overexpressed MANF specifically in DA neurons by using an α-synuclein Caenorhabditis elegans (C...
June 27, 2018: Experimental Neurology
P Capetian, N Stanslowsky, E Bernhardi, K Grütz, A Domingo, N Brüggemann, M Naujock, P Seibler, C Klein, F Wegner
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)...
June 23, 2018: Experimental Neurology
Marianna Kouskou, David M Thomson, Ros R Brett, Lee Wheeler, Rothwelle J Tate, Judith A Pratt, Luke H Chamberlain
Protein S-acylation is a widespread post-translational modification that regulates the trafficking and function of a diverse array of proteins. This modification is catalysed by a family of twenty-three zDHHC enzymes that exhibit both specific and overlapping substrate interactions. Mutations in the gene encoding zDHHC9 cause mild-to-moderate intellectual disability, seizures, speech and language impairment, hypoplasia of the corpus callosum and reduced volume of sub-cortical structures. 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...
June 23, 2018: Experimental Neurology
Eunjoo Lancaster, Jian Li, Taleen Hanania, Ronald Liem, Mark A Scheideler, Steven S Scherer
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)...
June 22, 2018: Experimental Neurology
Jinkun Wen, Dandan Tan, Lixia Li, Xianghai Wang, Mengjie Pan, Jiasong Guo
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...
June 22, 2018: Experimental Neurology
Zahra Jafari, Bryan E Kolb, Majid H Mohajerani
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...
June 21, 2018: Experimental Neurology
Renata Maciel, Dana Bis, Adriana P Rebelo, Cima Saghira, Stephan Züchner, Mario A Saporta
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...
June 20, 2018: Experimental Neurology
Tomomi Shijo, Hitoshi Warita, Naoki Suzuki, Kensuke Ikeda, Shio Mitsuzawa, Tetsuya Akiyama, Hiroya Ono, Ayumi Nishiyama, Rumiko Izumi, Yasuo Kitajima, Masashi Aoki
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...
June 19, 2018: Experimental Neurology
Sheng Yi, Lai Xu, Xiaosong Gu
Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft...
June 2, 2018: Experimental Neurology
Hale Yapıcı-Eser, Buket Dönmez-Demir, Kıvılcım Kılıç, Emine Eren-Koçak, Turgay Dalkara
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 aura and a measure of cortical excitability. CSD was induced by increasing concentrations of KCl applied over the dura with 5-minute intervals and recorded from parieto-occipital cortex to assess the CSD-induction threshold in acutely-stressed, chronically-stressed and naive mice...
May 29, 2018: Experimental Neurology
Jian-Long Zou, Jia-Hui Sun, Shuai Qiu, Shi-Hao Chen, Fu-Lin He, Jia-Chun Li, Hai-Quan Mao, Xiao-Lin Liu, Da-Ping Quan, Yuan-Shan Zeng, Qing-Tang Zhu
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...
May 29, 2018: Experimental Neurology
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