Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1 α/FNDC5/BDNF Pathway
This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal PGC-1 α, FNDC5, BDNF, and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young contr...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

The Transcriptional Regulatory Properties of Amyloid Beta 1 –42 may Include Regulation of Genes Related to Neurodegeneration
AbstractOur previous study demonstrated the translocation of A β1–42 to the nucleus in response to antibiotic treatment, and interpreted it as a possible transcriptional response of Aβ1–42 to antibiotics. The present study aims to investigate how amyloid acts on the key elements of neurodegeneration and the molecules involved in the induction of Aβ1–42 production. For this purpose, we investigated the acute effect of Aβ1–42 on the transcriptional levels of genes that have roles in the mechanisms that produce Aβ itself: alpha secretase (ADAM10), beta secretase (BACE1), the ga...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

CD271+, CXCR7+, CXCR4+, and CD133+ Stem/Progenitor Cells and Clinical Characteristics of Acute Ischemic Stroke Patients
This study discovers possible activity of the CD45–CD34 + CD271+ progenitor/stem cells during the first 7 days after ischemic stroke, suggests associations of the CD45–CD34 + CD133+ cells with the neurological status of stroke patients, and some activity of the CD45–CD34 + CD133+, the CD45–CD34 + CXCR4+, and the CD45– CD34 + CXCR7+ progenitor/stem cells in the process of arterial remodeling. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Piperlongumine Improves Lipopolysaccharide-Induced Amyloidogenesis by Suppressing NF-KappaB Pathway
AbstractAmyloidogenesis is known to cause Alzheimer ’s disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF- κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i.p.) injection of LPS (...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann –Steiner Syndrome
AbstractA growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants inKMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann –Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation
AbstractReactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwag...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Potential Role of Brain-Derived Neurotrophic Factor and Dopamine Receptor D2 Gene Variants as Modifiers for the Susceptibility and Clinical Course of Wilson ’s Disease
This study aims to identify the potential association betweenBDNF andDRD2 gene polymorphisms and WD and its clinical characteristics. A total of 164 WD patients and 270 controls from India were included in this study. TwoBDNF polymorphisms [p.Val66Met (c.G196A) and c.C270T] and theDRD2 Taq1A (A2/A1 or C/T) polymorphism were examined for their association with WD and some of its clinical attributes, using polymerase chain reaction, restriction fragment length digestion, and bidirectional sequencing. The C allele and CC genotype ofBDNF C270T were significantly overrepresented among controls compared to WD patients. In additi...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Cerebrospinal Fluid C-Reactive Protein in Parkinson ’s Disease: Associations with Motor and Non-motor Symptoms
AbstractParkinson ’ disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non- motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-mot...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA
AbstractDocosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 ( ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA co uld be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditio...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Emerging Concepts in Brain Glucose Metabolic Functions: From Glucose Sensing to How the Sweet Taste of Glucose Regulates Its Own Metabolism in Astrocytes and Neurons
AbstractThe astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data i...
Source: NeuroMolecular Medicine - September 1, 2018 Category: Neurology Source Type: research

Overexpression of Human Mutant PANK2 Proteins Affects Development and Motor Behavior of Zebrafish Embryos
AbstractPantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenzyme A (CoA) biosynthesis. Most likely, an unbalance of the neuronal levels of this important cofactor represents the initial trigger of the neurodegenerative process, yet a complete understanding of the connection between PANK2 malfunctioning and neuronal death is lacking. Most PKAN patients carry muta...
Source: NeuroMolecular Medicine - August 23, 2018 Category: Neurology Source Type: research

Neuroprotective Effect of Hydrogen Sulfide in Hyperhomocysteinemia Is Mediated Through Antioxidant Action Involving Nrf2
AbstractHomocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (>  15 µM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced by auto-oxidation of Hcy have been implicated in HHcy-associated neurological conditions. Hydrog en sulfide (H2S) is emerging as a potent neuroprotective and neuromodulator molecule. The present study was aimed to evaluate the ability of NaHS (a source of H2S) to attenuate Hcy-indu...
Source: NeuroMolecular Medicine - August 13, 2018 Category: Neurology Source Type: research

DRD3 Gene and ADHD: A Pharmaco-Behavioural Genetic Study
The objective of this study is to conduct an exploratory analysis using a comprehensive approach to investigate the role of candidate genes. This approach combines a dimensional behavioural approach akin to Research Domain Criteria (RDoC), a pharmaco-dynamic evaluation of behaviours relevant to ADHD, together with association and linkage testing in a large sample of children with ADHD. Parents, teachers, and research staff evaluated children with ADHD under three experimental conditions (EC): 1  week of baseline observation, followed by 1 week of methylphenidate (MPH) and 1 week of placebo, administered in a...
Source: NeuroMolecular Medicine - July 26, 2018 Category: Neurology Source Type: research

Emerging Concepts in Brain Glucose Metabolic Functions: From Glucose Sensing to How the Sweet Taste of Glucose Regulates Its Own Metabolism in Astrocytes and Neurons
AbstractThe astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data i...
Source: NeuroMolecular Medicine - July 18, 2018 Category: Neurology Source Type: research

RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann –Steiner Syndrome
AbstractA growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants inKMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann –Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate...
Source: NeuroMolecular Medicine - July 16, 2018 Category: Neurology Source Type: research

Potential Role of Brain-Derived Neurotrophic Factor and Dopamine Receptor D2 Gene Variants as Modifiers for the Susceptibility and Clinical Course of Wilson ’s Disease
This study aims to identify the potential association betweenBDNF andDRD2 gene polymorphisms and WD and its clinical characteristics. A total of 164 WD patients and 270 controls from India were included in this study. TwoBDNF polymorphisms [p.Val66Met (c.G196A) and c.C270T] and theDRD2 Taq1A (A2/A1 or C/T) polymorphism were examined for their association with WD and some of its clinical attributes, using polymerase chain reaction, restriction fragment length digestion, and bidirectional sequencing. The C allele and CC genotype ofBDNF C270T were significantly overrepresented among controls compared to WD patients. In additi...
Source: NeuroMolecular Medicine - July 10, 2018 Category: Neurology Source Type: research

Cerebrospinal Fluid C-Reactive Protein in Parkinson ’s Disease: Associations with Motor and Non-motor Symptoms
AbstractParkinson ’ disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non- motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-mot...
Source: NeuroMolecular Medicine - July 6, 2018 Category: Neurology Source Type: research

Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1 α/FNDC5/BDNF Pathway
This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal PGC-1 α, FNDC5, BDNF, and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young contr...
Source: NeuroMolecular Medicine - July 3, 2018 Category: Neurology Source Type: research

The Transcriptional Regulatory Properties of Amyloid Beta 1 –42 may Include Regulation of Genes Related to Neurodegeneration
AbstractOur previous study demonstrated the translocation of A β1–42 to the nucleus in response to antibiotic treatment, and interpreted it as a possible transcriptional response of Aβ1–42 to antibiotics. The present study aims to investigate how amyloid acts on the key elements of neurodegeneration and the molecules involved in the induction of Aβ1–42 production. For this purpose, we investigated the acute effect of Aβ1–42 on the transcriptional levels of genes that have roles in the mechanisms that produce Aβ itself: alpha secretase (ADAM10), beta secretase (BACE1), the ga...
Source: NeuroMolecular Medicine - June 12, 2018 Category: Neurology Source Type: research

Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation
AbstractReactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwag...
Source: NeuroMolecular Medicine - May 30, 2018 Category: Neurology Source Type: research

Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA
AbstractDocosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 ( ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA co uld be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditio...
Source: NeuroMolecular Medicine - May 30, 2018 Category: Neurology Source Type: research

Piperlongumine Improves Lipopolysaccharide-Induced Amyloidogenesis by Suppressing NF-KappaB Pathway
AbstractAmyloidogenesis is known to cause Alzheimer ’s disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF- κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i.p.) injection of LPS (...
Source: NeuroMolecular Medicine - May 25, 2018 Category: Neurology Source Type: research

CD271+, CXCR7+, CXCR4+, and CD133+ Stem/Progenitor Cells and Clinical Characteristics of Acute Ischemic Stroke Patients
This study discovers possible activity of the CD45–CD34 + CD271+ progenitor/stem cells during the first 7 days after ischemic stroke, suggests associations of the CD45–CD34 + CD133+ cells with the neurological status of stroke patients, and some activity of the CD45–CD34 + CD133+, the CD45–CD34 + CXCR4+, and the CD45– CD34 + CXCR7+ progenitor/stem cells in the process of arterial remodeling. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - May 9, 2018 Category: Neurology Source Type: research

The Dynamics of Neurosteroids and Sex-Related Hormones in the Pathogenesis of Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is commonly diagnosed by vast extracellular amyloid deposits and existence of intracellular neurofibrillary tangles. In accordance with the literature, age-related loss of sex steroid hormones in either males or females was found in relation to AD subjects. The dynamics of these ho rmones have been previously described in both physiological and pathological conditions with the evidence of changes in various intracellular signalings regarding the neurodegenerative disease. The potent protective effects of sex steroid hormones and their synthetic analogs are indicative of the de crease...
Source: NeuroMolecular Medicine - May 4, 2018 Category: Neurology Source Type: research

Association of CALM1 rs3179089 Polymorphism with Ischemic Stroke in Chinese Han Population
This study aims to evaluate the relationship betweenCALM1 rs3179089 polymorphism and ischemic stroke (IS) in Chinese Han population. A total of 550 patients with IS and 550 control subjects were recruited and genotyped using Sequenom MassArray technology. The mRNA expression ofCALM1 was measured using quantitative real-time polymerase chain reaction.CALM1 mRNA expression was significantly higher in patients with IS than that in control subjects (P = 0.006). The genomic frequency distribution was significantly different between female patients with IS and female controls (χ2 = 6.043,P ...
Source: NeuroMolecular Medicine - April 30, 2018 Category: Neurology Source Type: research

BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H 2 S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress
AbstractOur previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found th...
Source: NeuroMolecular Medicine - April 27, 2018 Category: Neurology Source Type: research

How to Spot Congenital Myasthenic Syndromes Resembling the Lambert –Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features
AbstractCongenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert –Eaton myasthenic syndrome (CMS–LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimu lation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. C...
Source: NeuroMolecular Medicine - April 25, 2018 Category: Neurology Source Type: research

Improved Bioavailability of Levodopa Using Floatable Spray-Coated Microcapsules for the Management of Parkinson ’s Disease
AbstractOral administration of levodopa (LD) is the gold standard in managing Parkinson ’s disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated w ith an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuati...
Source: NeuroMolecular Medicine - April 25, 2018 Category: Neurology Source Type: research

Neuroimmunologic and Neurotrophic Interactions in Autism Spectrum Disorders: Relationship to Neuroinflammation
AbstractAutism spectrum disorders (ASD) are the most prevalent set of pediatric neurobiological disorders. The etiology of ASD has both genetic and environmental components including possible dysfunction of the immune system. The relationship of the immune system to aberrant neural circuitry output in the form of altered behaviors and communication characterized by ASD is unknown. Dysregulation of neurotrophins such as BDNF and their signaling pathways have been implicated in ASD. While abnormal cortical formation and autistic behaviors in mouse models of immune activation have been described, no one theory has been descri...
Source: NeuroMolecular Medicine - April 24, 2018 Category: Neurology Source Type: research

Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics
AbstractA perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell –cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emph asis on induction of autophagy and mitochondrial biogenesis. Monocrotophos (MCP), a widely used neurotoxic organophos...
Source: NeuroMolecular Medicine - March 30, 2018 Category: Neurology Source Type: research

Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway –PPAR Gamma, Energy Metabolism and Circadian Rhythms
AbstractEntropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington ’s disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer’s disease and Parkinson’s disease, WNT/beta-catenin pathway is...
Source: NeuroMolecular Medicine - March 23, 2018 Category: Neurology Source Type: research

GWAS-Supported CRP Gene Polymorphisms and Functional Outcome of Large Artery Atherosclerotic Stroke in Han Chinese
This study aimed to investigate the association betweenCRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) inCRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3  months after the index stroke was assessed by the modified Rankin scale. Associations between ge...
Source: NeuroMolecular Medicine - March 19, 2018 Category: Neurology Source Type: research

Vitamin D 3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke
AbstractAcute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100  ng/kg/day) or vehicle i.p. for 5 day prior to stroke. Stroke was induced via middle cerebral art...
Source: NeuroMolecular Medicine - February 23, 2018 Category: Neurology Source Type: research

Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T + Itpr3 tf /J Mice
AbstractAutism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf/J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach. Here, we explored whether resveratr...
Source: NeuroMolecular Medicine - February 21, 2018 Category: Neurology Source Type: research

Differential Binding of Human ApoE Isoforms to Insulin Receptor is Associated with Aberrant Insulin Signaling in AD Brain Samples
In this study, we investigated the effect of ApoE genotype on the insulin signaling pathway in control and AD human brain samples. We found that targets of the insulin signaling pathway were attenuated in AD cases, regardless of ApoE isoform. We also found a decrease in GluR1 subunit expression, and an increase NR2B subunit expression in AD cases, regardless of ApoE isoform. Lastly, we observed that more insulin receptor (IR) was immunoprecipitated in control cases, and more Aβ was immunoprecipitated with AD cases. But, when comparing among AD cases, we found that more IR was immunoprecipitated with ApoE3 than ApoE4, ...
Source: NeuroMolecular Medicine - February 15, 2018 Category: Neurology Source Type: research

Correction of Huntington ’s Disease Phenotype by Genistein-Induced Autophagy in the Cellular Model
AbstractHuntington ’s disease (HD) is a monogenic disorder, caused by mutations in theHTT gene which result in expansion of CAG triplets. The product of the mutated gene is misfolded huntingtin protein that forms aggregates leading to impairment of neuronal function, neurodegeneration, motor abnormalities and cognitive deficits. No effective cure is currently available for HD. Here we studied effects of genistein (trihydroxyisoflavone) on a HD cellular model consisting of HEK-293 cells transfected with a plasmid bearing mutatedHTT gene. Both level of mutated huntingtin and number of aggregates were significantly decr...
Source: NeuroMolecular Medicine - February 12, 2018 Category: Neurology Source Type: research

Cardiovascular Autonomic Dysfunction: Link Between Multiple Sclerosis Osteoporosis and Neurodegeneration
AbstractThe high prevalence of osteoporosis, observed in multiple sclerosis (MS) patients, has been attributed to reduced mobility and or the use of disease-modifying drugs. However, MS-impaired cardiovascular autonomic nervous system (ANS) function has the potential of reducing bone mass density (BMD) by altering the expression and/or function of the neuronal, systemic, and local mediators of bone remodeling. This review describes the complex regulation of bone homeostasis with a focus on MS, providing evidence that ANS dysfunction and low BMD are intertwined with MS inflammatory and neurodegenerative processes, and with ...
Source: NeuroMolecular Medicine - February 10, 2018 Category: Neurology Source Type: research

Molecular Insights into the Roles of Rab Proteins in Intracellular Dynamics and Neurodegenerative Diseases
AbstractIn eukaryotes, the cellular functions are segregated to membrane-bound organelles. This inherently requires sorting of metabolites to membrane-limited locations. Sorting the metabolites from ribosomes to various organelles along the intracellular trafficking pathways involves several integral cellular processes, including an energy-dependent step, in which the sorting of metabolites between organelles is catalyzed by membrane-anchoring protein Rab-GTPases (Rab). They contribute to relaying the switching of the secretory proteins between hydrophobic and hydrophilic environments. The intracellular trafficking routes ...
Source: NeuroMolecular Medicine - February 8, 2018 Category: Neurology Source Type: research

Neuroprotective Effect and Mechanism of Action of Tetramethylpyrazine Nitrone for Ischemic Stroke Therapy
AbstractOur previous studies demonstrated that the multifunctional agent TBN, a derivative of tetramethylpyrazine armed with a nitrone moiety, displayed high therapeutic efficacy in experimental ischemic stroke models. However, its molecular mechanisms of action underlying the neuroprotective effect need further exploration. In the present study, we found that TBN had significant activities scavenging free radicals such as·OH, O2·− and ONOO−, inhibiting Ca2+ overload, maintaining mitochondrial function and preventing neuronal damage in primary cortical cultures. Further, TBN was effective in reduc...
Source: NeuroMolecular Medicine - February 6, 2018 Category: Neurology Source Type: research

NMDA Receptor GluN2 Subtypes Control Epileptiform Events in the Hippocampus
AbstractNMDA receptors (NMDARs) play a key role in synaptic plasticity and excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging area. Recent studies have revealed that mutations in NMDARs are a cause for epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus, expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally regulated. However, the pharmacological significance of these subtypes is not well understood in epileptic context/models. To investigate this, epilepsy was induced in hippocampal slices by the application of artificial cerebrospinal fluid that ...
Source: NeuroMolecular Medicine - January 15, 2018 Category: Neurology Source Type: research

Behavioral, Biochemical and Molecular Characterization of a Parkinson ’s Disease Mouse Model Using the Neurotoxin 2′-CH 3 -MPTP: A Novel Approach
AbstractThe neurotoxin MPTP has long been used to create a mouse model of Parkinson ’s disease (PD). Indeed, several MPTP analogues have been developed, including 2′-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2 ′-CH3-MPTP has been carried out so far. In the present work, 2 ′-CH3-MPTP was administered to mice (2.5, 5.0 and 10  mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated. We show that, de...
Source: NeuroMolecular Medicine - January 13, 2018 Category: Neurology Source Type: research

Serum Mortalin Correlated with α-Synuclein as Serum Markers in Parkinson’s Disease: A Pilot Study
This study aims to estimate the Mortalin concentration in serum and correlate with α-synuclein (α-Syn) in PD. The concentration of Mortalin and α-Syn in serum samples of 38 PD patients and 33 control group (CG) individuals was quantified by surface plasmon resonance. The receiv er operating characteristic curves were plotted to develop it as blood-based protein marker. The expression of Mortalin in serum was validated by western blot. The Mortalin level was found to be declined in PD patients (1.98 ± 0.53 ng/µL) in comparison with CG individuals (3.13 ± 0.48&nb...
Source: NeuroMolecular Medicine - January 6, 2018 Category: Neurology Source Type: research

Genetics and Treatment Response in Parkinson ’s Disease: An Update on Pharmacogenetic Studies
AbstractParkinson ’s disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopamine neurons of the central nervous system. The disease determines a significant disability due to a combination of motor symptoms such as bradykinesia, rigidity and rest tremor and non-motor symptom s such as sleep disorders, hallucinations, psychosis and compulsive behaviors. The current therapies consist in combination of drugs acting to control only the symptoms of the illness by the replacement of the dopamine lost. Although patients generally receive benefits from this symptomatic pharmaco logica...
Source: NeuroMolecular Medicine - January 5, 2018 Category: Neurology Source Type: research

Combination Therapy with Low-Dose IVIG and a C1-esterase Inhibitor Ameliorates Brain Damage and Functional Deficits in Experimental Ischemic Stroke
AbstractAcute ischemic stroke causes a high rate of deaths and permanent neurological deficits in survivors. Current interventional treatment, in the form of enzymatic thrombolysis, benefits only a small percentage of patients. Brain ischemia triggers mobilization of innate immunity, specifically the complement system and Toll-like receptors (TLRs), ultimately leading to an exaggerated inflammatory response. Here we demonstrate that intravenous immunoglobulin (IVIG), a scavenger of potentially harmful complement fragments, and C1-esterase inhibitor (C1-INH), an inhibitor of complement activation, exert a beneficial effect ...
Source: NeuroMolecular Medicine - January 3, 2018 Category: Neurology Source Type: research

Inhibition of GSK-3beta Signaling Pathway Rescues Ketamine-Induced Neurotoxicity in Neural Stem Cell-Derived Neurons
AbstractClinical application of anesthetic reagent, ketamine (Keta), may induce irreversible neurotoxicity in central nervous system. In this work, we utilized an in vitro model of neural stem cells-derived neurons (nSCNs) to evaluate the role of GSK-3 signaling pathway in Keta-induced neurotoxicity. Embryonic mouse-brain neural stem cells were differentiated into neurons in vitro. Keta (50  μM)-induced neurotoxicity in cultured nSCNs was monitored by apoptosis, immunohistochemical and western blot assays, respectively. GSK-3 signaling pathways, including GSK-3α and GSK-3β, were inhibited by siRNA in the...
Source: NeuroMolecular Medicine - December 7, 2017 Category: Neurology Source Type: research

STAT4 Polymorphisms are Associated with Neuromyelitis Optica Spectrum Disorders
AbstractSTAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case –control study to determine whetherSTAT4 contributed to the risk of NMOSD. We tested fiveSTAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to iden...
Source: NeuroMolecular Medicine - November 9, 2017 Category: Neurology Source Type: research

Elevated Plasma Level of Soluble Form of RAGE in Ischemic Stroke Patients with Dementia
This study aimed to investigate the associations of the plasma levels of sRAGE and esRAGE in ischemic stroke (IS) patients with and without dementia. This cross-sectional study recruited patients with IS at a university medical center. Vascular dementia was defined as the scale of Clinical Dementia Ranking (CDR)  ≥ 1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of sRAGE and esRAGE. From November 2014 to October 2015, a total of 172 IS patients (mean age: 72.1 ± 7.5 years, 64.5% male) were recruited, including 73 with CDR = 0, 63 with C...
Source: NeuroMolecular Medicine - November 2, 2017 Category: Neurology Source Type: research

(E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates LPS-Mediated Memory Impairment by Inhibition of STAT3 Pathway
We examined whether MMPP (5 mg/kg in drinking water for 1 month) prevents amyloidogenesis and cognitive impairment on AD model mice induced by intraperitoneal LPS (250 μg/kg daily 7 times) injections. Additionally, we investigated the anti-neuroinflamma tory and anti-amyloidogenic effect of MMPP (1, 5, and 10 μg/mL) in LPS (1 μg/mL)-treated cultured astrocytes and microglial BV-2 cells. MMPP treatment reduced LPS-induced memory loss. This memory recovery effect was associated with the reduction of LPS-induced inflammatory proteins; cyclooxygena se-2 (COX-2) and inducible nitric oxide synth...
Source: NeuroMolecular Medicine - October 19, 2017 Category: Neurology Source Type: research

The UCP2-866G/A Polymorphism Could be Considered as a Genetic Marker of Different Functional Prognosis in Ischemic Stroke After Recanalization
AbstractRecent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization. We investigate a hospital-based prospective cohort of patients with acute ischemic stroke ...
Source: NeuroMolecular Medicine - October 17, 2017 Category: Neurology Source Type: research