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ASN Neuro

Jingjing Cheng, Qingqing Lu, Li Song, Margaret S Ho
Protein aggregation and accumulation are common pathological hallmarks in neurodegenerative diseases. To efficiently clear and eliminate such aggregation becomes an important cellular strategy for cell survival. Lewy bodies inclusion and aggregation of α-Synuclein (α-Syn) during the pathogenesis of Parkinson's disease (PD) serve as a good example and are potentially linked to other pathological PD features such as progressive dopaminergic neuron cell death, behavioral defects, and nonmotor symptoms like anosmia, cognitive impairment, and depression...
January 2018: ASN Neuro
Yixian Huang, Haiyang Shu, Li Li, Tili Zhen, Junyan Zhao, Xianju Zhou, Weifeng Luo
Levodopa (L-DOPA) is still the most effective drug for the treatment of Parkinson's disease (PD). However, the long-term therapy often triggers L-DOPA-induced dyskinesia (LID). Metabotropic glutamate receptor type 5 (mGluR5) is abundant in the basal ganglia, and its inhibition is thought to modulate postsynaptic excitatory synaptic transmission and glutamate hyperactivity in PD and LID. In this report, we examined the effects of mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on LID and synaptic components in the PD model rat...
January 2018: ASN Neuro
Ji Heun Jeong, Do Kyung Kim, Nam-Seob Lee, Young-Gil Jeong, Ho Won Kim, Jong-Seok Kim, Seung-Yun Han
Hyperammonemia associated with overt hepatic encephalopathy (OHE) causes excitotoxic neuronal death through activation of the cytochrome C (CytC)-mediated mitochondria-dependent apoptotic pathway. We tested the therapeutic effect of nortriptyline (NT), a mitochondrial permeability transition pore (mPTP) blocker that can possibly inhibit mitochondrial CytC efflux to the cytosol on in vivo and in vitro OHE models. After ensuring the generation of OHE rats, established by bile duct ligation (BDL), they were intraperitoneally administered either 20 mg/kg NT (i...
January 2018: ASN Neuro
Danielle C Robinson, Anna E Mammel, Anne M Logan, Aubree A Larson, Eric J Schmidt, Alec F Condon, Fred L Robinson
Charcot-Marie-Tooth Disorder Type 4B (CMT4B) is a demyelinating peripheral neuropathy caused by mutations in myotubularin-related (MTMR) proteins 2, 13, or 5 (CMT4B1/2/3), which regulate phosphoinositide turnover and endosomal trafficking. Although mouse models of CMT4B2 exist, an in vitro model would make possible pharmacological and reverse genetic experiments needed to clarify the role of MTMR13 in myelination. We have generated such a model using Schwann cell-dorsal root ganglion (SC-DRG) explants from Mtmr13-/- mice...
January 2018: ASN Neuro
Maham Rais, Devin K Binder, Khaleel A Razak, Iryna M Ethell
Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability. It is a leading known genetic cause of autism. In addition to cognitive, social, and communication deficits, humans with FXS demonstrate abnormal sensory processing including sensory hypersensitivity. Sensory hypersensitivity commonly manifests as auditory, tactile, or visual defensiveness or avoidance. Clinical, behavioral, and electrophysiological studies consistently show auditory hypersensitivity, impaired habituation to repeated sounds, and reduced auditory attention in humans with FXS...
January 2018: ASN Neuro
Xinze Peng, Abdullah M Madany, Jessica C Jang, Joseph M Valdez, Zuivanna Rivas, Abigail C Burr, Yelena Y Grinberg, Tara M Nordgren, Meera G Nair, David Cocker, Monica J Carson, David D Lo
Continuous exposure to aerosolized fine (particle size ≤2.5 µm) and ultrafine (particle size ≤0.1 µm) particulates can trigger innate inflammatory responses in the lung and brain depending on particle composition. Most studies of manmade toxicants use inhalation exposure routes, whereas most studies of allergens use soluble solutions administered via intranasal or injection routes. Here, we tested whether continuous inhalation exposure to aerosolized Alternaria alternata particulates (a common fungal allergen associated with asthma) would induce innate inflammatory responses in the lung and brain...
January 2018: ASN Neuro
Irene L Gutiérrez, Marta González-Prieto, Borja García-Bueno, Javier R Caso, Juan C Leza, José L M Madrigal
Fluoro-Jade is a fluorescein-derived fluorochrome which specifically binds to damaged neurons. Due to this characteristic, it is commonly used for the histochemical detection and quantification of neurodegeneration in mounted brain sections. Here, we describe an alternative and simpler histochemistry protocol based on the use of free-floating brain sections. For this purpose, we have used brain slices from wild-type and 5xFAD mice as well as from mice that received an intracerebral injection of oligomeric amyloid beta peptides...
January 2018: ASN Neuro
Eric M Gold, Vitaly Vasilevko, Jonathan Hasselmann, Casey Tiefenthaler, Danny Hoa, Kasuni Ranawaka, David H Cribbs, Brian J Cummings
An estimated 5.3 million Americans are living with a disability from a traumatic brain injury (TBI). There is emerging evidence of the detrimental effects from repeated mild TBIs (rmTBIs). rmTBI manifests its own unique set of behavioral and neuropathological changes. A subset of individuals exposed to rmTBI develop permanent behavioral and pathological consequences, defined postmortem as chronic traumatic encephalopathy. We have combined components of two classic rodent models of TBI, the controlled cortical impact model and the weight drop model, to develop a repeated mild closed head injury (rmCHI) that produces long-term deficits in several behaviors that correlate with neuropathological changes...
January 2018: ASN Neuro
T N Seyfried, H Choi, A Chevalier, D Hogan, Z Akgoc, J S Schneider
Parkinson's disease (PD) is a neurodegenerative movement disorder involving the selective loss of dopamine-producing neurons in the substantia nigra (SN). Differences in disease presentation, prevalence, and age of onset have been reported between males and females with PD. The content and composition of the major glycosphingolipids, phospholipids, and cholesterol were evaluated in the SN from 12 PD subjects and in 18 age-matched, neurologically normal controls. Total SN ganglioside sialic acid content and water content (%) were significantly lower in the male PD subjects than in the male controls...
January 2018: ASN Neuro
Rui-Ming Guo, Cheng-Bin Zhao, Peng Li, Liang Zhang, Su-Hua Zang, Bo Yang
C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients' prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan-Meier survival and the Cox proportional hazard model...
January 2018: ASN Neuro
Xian-Si Zeng, Wen-Shuo Geng, Jin-Jing Jia
Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies...
January 2018: ASN Neuro
James Cao, Yanping Hu, Mohammed Salman Shazeeb, Carlos E Pedraza, Nilesh Pande, Daniel Weinstock, Gregory H Polites, Wenfei Zhang, Karen J Chandross, Xiaoyou Ying
The compact myelin sheath is important for axonal function, and its loss can lead to neuronal cell death and irreversible functional deficits. Myelin is vulnerable to a variety of metabolic, toxic, and autoimmune insults. In diseases like multiple sclerosis, there is currently no therapy to stop myelin loss, underscoring the need for neuroprotective and remyelinating therapies. Noninvasive, robust techniques are also needed to confirm the effect of such therapies in animal models. This article describes the generation, characterization, and potential uses for a myelin basic protein-luciferase (MBP-luci) transgenic mouse model, in which the firefly luciferase reporter gene is selectively controlled by the MBP promoter...
January 2018: ASN Neuro
Kyoko Mashima, Shinichi Takahashi, Kazushi Minami, Yoshikane Izawa, Takato Abe, Naoki Tsukada, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki
Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice...
January 2018: ASN Neuro
Emin Fidan, Lesley M Foley, Lee Ann New, Henry Alexander, Patrick M Kochanek, T Kevin Hitchens, Hülya Bayır
Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes using diffusion tensor imaging of the whole brain and proton magnetic resonance spectroscopy of the hippocampi at 7 Tesla in 18-day-old male rats at 7 days after mTBI and rmTBI...
January 2018: ASN Neuro
Ryan B Griggs, Leonid M Yermakov, Domenica E Drouet, Duc V M Nguyen, Keiichiro Susuki
Nodes of Ranvier and associated paranodal and juxtaparanodal domains along myelinated axons are essential for normal function of the peripheral and central nervous systems. Disruption of these domains as well as increases in the reactive carbonyl species methylglyoxal are implicated as a pathophysiology common to a wide variety of neurological diseases. Here, using an ex vivo nerve exposure model, we show that increasing methylglyoxal produces paranodal disruption, evidenced by disorganized immunostaining of axoglial cell-adhesion proteins, in both sciatic and optic nerves from wild-type mice...
January 2018: ASN Neuro
(no author information available yet)
Lavezzi, A. M., Ferrero, S., Roncati, L., Piscioli, F., Matturri, L. & Pusiol, T. (2017). Nicotinic receptor abnormalities in the cerebellar cortex of sudden unexplained fetal and infant death victims-possible correlation with maternal smoking. ASN Neuro, 9, 1-10. DOI: 10.1177/1759091417720582 In figure 4, one of the labels mentioned at the bottom of graph is incorrect. Instead of "BDNF-index classes", the label should be " nAChR-index". The correct figure is shown below.
January 2018: ASN Neuro
Angela M Muller, Naznin Virji-Babul
Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions ( n = 6) and a group of healthy adolescent athletes ( n = 6)...
January 2018: ASN Neuro
Michael Rudy, Margot Mayer-Proschel
Iron deficiency (ID) affects more than three billion people worldwide making it the most common micronutrient deficiency. ID is most prevalent during gestation and early life, which is of particular concern since its impact on the developing central nervous system is associated with an increased risk of a wide range of different psychiatric disorders later in life. The cause for this association is not known, but many of these same disorders are also associated with an imbalance between excitation and inhibition (E/I) within the brain...
November 2017: ASN Neuro
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
Erica M Weekman, Abigail E Woolums, Tiffany L Sudduth, Donna M Wilcock
High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr...
November 2017: ASN Neuro
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