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Neuromolecular Medicine

Saif Ahmad, Kanchan Bhatia, Adam Kindelin, Andrew F Ducruet
The complement system is a key regulator of the innate immune response against diseased tissue that functions across multiple organ systems. Dysregulation of complement contributes to the pathogenesis of a number of neurological diseases including stroke. The C3a anaphylatoxin, via its cognate C3a receptor (C3aR), mediates inflammation by promoting breakdown of the blood-brain barrier and the massive infiltration of leukocytes into ischemic brain in experimental stroke models. Studies utilizing complement deficient mice as well as pharmacologic C3aR antagonists have shown a reduction in tissue injury and mortality in murine stroke models...
May 17, 2019: Neuromolecular Medicine
Yuki Kishimoto, Wandi Zhu, Waki Hosoda, Jyoti M Sen, Mark P Mattson
Emerging findings suggest that Parkinson's disease (PD) pathology (α-synuclein accumulation) and neuronal dysfunction may occur first in peripheral neurons of the autonomic nervous system including the enteric branches of the vagus nerve. The risk of PD increases greatly in people over the age of 65, a period of life in which chronic inflammation is common in many organ systems including the gut. Here we report that chronic mild focal intestinal inflammation accelerates the age of disease onset in α-synuclein mutant PD mice...
May 11, 2019: Neuromolecular Medicine
Koteswara Rao Nalamolu, Ishwarya Venkatesh, Adithya Mohandass, Jeffrey D Klopfenstein, David M Pinson, David Z Wang, Adinarayana Kunamneni, Krishna Kumar Veeravalli
Emerging stroke literature suggests that treatment of experimentally induced stroke with stem cells offered post-stroke neuroprotection via exosomes produced by these cells. Treatment with exosomes has great potential to overcome the limitations associated with cell-based therapies. However, in our preliminary studies, we noticed that the exosomes released from human umbilical cord blood-derived mesenchymal stem cells (MSCs) under standard culture conditions did not improve the post-stroke neurological outcome...
May 10, 2019: Neuromolecular Medicine
Zhen Xu, Yan-Ning Rui, John P Hagan, Dong H Kim
Intracranial aneurysms (IA) are local dilatations in cerebral arteries that predominantly affect the circle of Willis. Occurring in approximately 2-5% of adults, these weakened areas are susceptible to rupture, leading to subarachnoid hemorrhage (SAH), a type of hemorrhagic stroke. Due to its early age of onset and poor prognosis, SAH accounts for > 25% of years lost for all stroke victims under the age of 65. In this review, we describe the cerebrovascular pathology associated with intracranial aneurysms...
May 4, 2019: Neuromolecular Medicine
Mohd Tayyab, Shirin Farheen, Mubeena Mariyath P M, Nabeela Khanam, M Mobarak Hossain, Mehdi Hayat Shahi
Depression is one of the most prevalent and crucial public health problem connected to significant mortality and co-morbidity. Recently, numerous studies suggested that dietary flavanones exhibit neuroprotective and antidepressant effects against various psycho-physiological conditions including depression. The present study is focused on the antidepressant and neuroprotective effects of naringenin (NAR) and the involvement of sonic hedgehog (Shh) signaling in the chronic unpredictable mild stress (CUMS)-induced depression...
April 29, 2019: Neuromolecular Medicine
Wei-Wen Zhu, Min Ning, Yi-Zhu Peng, Yi-Yun Tang, Xuan Kang, Ke-Bin Zhan, Wei Zou, Ping Zhang, Xiao-Qing Tang
It has been previously demonstrated that hydrogen sulfide (H2 S) prevents formaldehyde (FA)-induced neurotoxicity. However, the exact mechanisms underlying this protection remain to be fully elucidated. Neuronal senescence is involved in FA-induced neurotoxicity. Leptin signaling has anti-aging function. The present work was to investigate the protection of H2 S against FA-induced neuronal senescence and the mediatory role of leptin signaling. FA-exposed HT-22 cells were used as the vitro model of FA-induced neuronal senescence...
April 12, 2019: Neuromolecular Medicine
Abhishek Jauhari, Sanjay Yadav
Studies from last two decades have established microRNAs (miRNAs) as the most influential regulator of gene expression, especially at the post-transcriptional stage. The family of small RNA molecules including miRNAs is highly conserved and expressed throughout the multicellular organism. MiRNAs regulate gene expression by binding to 3' UTR of protein-coding mRNAs and initiating either decay or movement of mRNAs to stress granules. Tissues or cells, which go through cell fate transformation like stem cells, brain cells, iPSCs, or cancer cells show very dynamic expression profile of miRNAs...
April 8, 2019: Neuromolecular Medicine
Saranya Suriyanarayanan, Alaa Othman, Bianca Dräger, Anja Schirmacher, Peter Young, Lejla Mulahasanovic, Konstanze Hörtnagel, Saskia Biskup, Arnold von Eckardstein, Thorsten Hornemann, Museer A Lone
Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare, autosomal dominantly inherited, slowly progressive and length-dependent axonal peripheral neuropathy. HSAN1 is associated with several mutations in serine-palmitoyltransferase (SPT), the first enzyme in the de novo sphingolipid biosynthetic pathway. HSAN1 mutations alter the substrate specificity of SPT, which leads to the formation of 1-deoxysphingolipids, an atypical and neurotoxic subclass of sphingolipids. This study describes the clinical and neurophysiological phenotype of a German family with a novel SPTCL2 mutation (c...
April 6, 2019: Neuromolecular Medicine
Stefano Pianta, Jea Young Lee, Julian P Tuazon, Vanessa Castelli, Leigh Monica Mantohac, Naoki Tajiri, Cesar V Borlongan
Stroke remains a significant unmet clinical need with limited therapeutic options. The peculiar feature of ischemic stroke is the interruption in brain circulation, resulting in a cascade of detrimental cerebrovasculature alterations. Treatment strategies designed to maintain potency of the cerebrovasculature may protect against stroke. The present study assessed the effects of short bouts of exercise prior to stroke induction and characterized cerebral blood flow and motor functions in vivo. Adult Sprague-Dawley rats were exposed to a single short bout of exercise (30-min or 60-min forced running wheel) then subjected to transient middle cerebral artery occlusion (MCAO)...
April 2, 2019: Neuromolecular Medicine
Shaho Parvin, Maryam Rezazadeh, Hassan Hosseinzadeh, Mohsen Moradi, Shadi Shiva, Jalal Gharesouran
Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders caused by mutations in fourteen distinct ceroid lipofuscinoses, neuronal (CLN) genes described with various severe symptoms such as seizures, visual failure, motor decline, and progressive cognitive deterioration. The current research represents novel CLN5 (c.741G > A) and CLN8 (c.565delT) mutations in two different Iranian families with late-infantile NCL (LINCL) and their relatives by using whole-exome sequencing (WES)...
March 27, 2019: Neuromolecular Medicine
Shyanne Page, Snehal Raut, Abraham Al-Ahmad
The blood-brain barrier (BBB) plays an important role in brain homeostasis. Hypoxia/ischemia constitutes an important stress factor involved in several neurological disorders by inducing the disruption of the BBB, ultimately leading to cerebral edema formation. Yet, our current understanding of the cellular and molecular mechanisms underlying the BBB disruption following cerebral hypoxia/ischemia remains limited. Stem cell-based models of the human BBB present some potentials to address such issues. Yet, such models have not been validated in regard of its ability to respond to hypoxia/ischemia as existing models...
March 26, 2019: Neuromolecular Medicine
Brian B Griffiths, Peyman Sahbaie, Anand Rao, Oiva Arvola, Lijun Xu, Deyong Liang, Yibing Ouyang, David J Clark, Rona G Giffard, Creed M Stary
Mild traumatic brain injury (mTBI) can result in permanent impairment in memory and learning and may be a precursor to other neurological sequelae. Clinical treatments to ameliorate the effects of mTBI are lacking. Inhibition of microRNA-181a (miR-181a) is protective in several models of cerebral injury, but its role in mTBI has not been investigated. In the present study, miR-181a-5p antagomir was injected intracerebroventricularly 24 h prior to closed-skull cortical impact in young adult male mice. Paw withdrawal, open field, zero maze, Y maze, object location and novel object recognition tests were performed to assess neurocognitive dysfunction...
March 21, 2019: Neuromolecular Medicine
Micaela Fredi, Ilaria Cavazzana, Giorgio Biasiotto, Massimiliano Filosto, Alessandro Padovani, Eugenio Monti, Angela Tincani, Franco Franceschini, Isabella Zanella
The commonest genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a large hexanucleotide expansion within the non-coding region of the C9orf72 gene. The pathogenic mechanisms of the mutation seem toxic gain of functions, while haploinsufficiency alone appears insufficient to cause neurodegeneration. C9orf72-/- mice rather develop features of autoimmunity. Immune-mediated dysfunctions are involved in the pathogenesis of ALS and FTD and high prevalence of autoimmune disease has recently been observed in C9orf72 expansion-positive patients...
March 11, 2019: Neuromolecular Medicine
Joseph Kamtchum-Tatuene, Glen C Jickling
Biomarkers are objective indicators used to assess normal or pathological processes, evaluate responses to treatment and predict outcomes. Many blood biomarkers already guide decision-making in clinical practice. In stroke, the number of candidate biomarkers is constantly increasing. These biomarkers include proteins, ribonucleic acids, lipids or metabolites. Although biomarkers have the potential to improve the diagnosis and the management of patients with stroke, there is currently no marker that has demonstrated sufficient sensitivity, specificity, rapidity, precision, and cost-effectiveness to be used in the routine management of stroke, thus highlighting the need for additional work...
March 4, 2019: Neuromolecular Medicine
Xiao Miao, Bin Fan, Rongqun Li, Shaoping Zhang, Honghuang Lin
Major depressive disorder is a common debilitating disorder that is associated with increased morbidity and mortality. However, the molecular mechanism underlying depression remains largely unknown. The current study investigated the association of depression with blood gene expression using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Depression was measured by the geriatric depression scale, and the blood gene expression was measured by the Affymetrix Human Genome U219 Array. Linear regression was used to test the association between gene expression and depression, and the model was adjusted for age and sex...
March 1, 2019: Neuromolecular Medicine
Gahee Bahn, Dong-Gyu Jo
The nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2) is a master transcription factor that regulates oxidative stress-related genes containing the antioxidant response element (ARE) in their promoters. The damaged function and altered localization of NRF2 are found in most neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis. These neurodegenerative diseases developed from various risk factors such as accumulated oxidative stress and genetic and environmental elements...
March 2019: Neuromolecular Medicine
Elham Sadat Sayed Javad Javaheri, Mohammad Reza Bigdeli, Mohammad Ismail Zibaii, Leila Dargahi, Hamid Reza Pouretemad
Epigenetic agents, such as neonatal isolation during neurodevelopmental period of life, can change various regions of the brain. It may further induce psychological disorders such as autistic-like phenomena. This study indicated the role of chronic increased anterior cingulate cortex (ACC) output on alteration of caudate putamen (CPu) as a main behavior regulator region of the brain in adult maternal deprived (MD) rats. For making an animal model, neonates were isolated from their mothers in postnatal days (PND 1-10, 3 h/day)...
February 19, 2019: Neuromolecular Medicine
Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K Sumbria
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia...
January 17, 2019: Neuromolecular Medicine
Djenifer B Kappel, Jaqueline B Schuch, Diego L Rovaris, Bruna S da Silva, Diana Müller, Vitor Breda, Stefania P Teche, Rudimar S Riesgo, Lavínia Schüler-Faccini, Luís A Rohde, Eugenio H Grevet, Claiton H D Bau
Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD)...
January 16, 2019: Neuromolecular Medicine
Hareram Birla, Sachchida Nand Rai, Saumitra Sen Singh, Walia Zahra, Arun Rawat, Neeraj Tiwari, Rakesh K Singh, Abhishek Pathak, Surya Pratap Singh
Parkinson's disease (PD), a neurodegenerative central nervous system disorder, is characterised by progressive loss of nigrostriatal neurons in basal ganglia. Previous studies regarding PD have suggested the role of oxidative stress along with neuroinflammation in neurodegeneration. Accordingly, our study explore the anti-inflammatory activity of Tinospora cordifolia aqueous extract (TCAE) in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)-intoxicated Parkinsonian mouse model. MPTP-intoxicated mice showed significant behavioral and biochemical abnormalities which were effectively reversed by TCAE...
January 14, 2019: Neuromolecular Medicine
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