Safflower Yellow Improves Synaptic Plasticity in APP/PS1 Mice by Regulating Microglia Activation Phenotypes and BDNF/TrkB/ERK Signaling Pathway
In this study, we are going to study the mechanism of how SY treats AD in terms of synaptic plasticity. We found, via behavioral experiments, that SY treatment could improve the abilities of learning and memory in APP/PS1 mice. In addition, using Golgi staining and HE staini ng, we found that SY treatment could reduce the loss of dendritic spines in the pathological condition and could maintain the normal physiological state of the cells in cortex and in hippocampus. In addition, the results of immunofluorescence staining and western blotting showed that SY treatment co uld significantly increase the expression of synapse-...
Source: NeuroMolecular Medicine - February 11, 2020 Category: Neurology Source Type: research

Impact of Maternal Separation on Dopamine System and its Association with Parkinson's Disease
AbstractAs a type of stress, maternal separation (MS) has been one of the most widely used models in neuropsychiatric research. An increasing number of studies has found that MS not only affects the function of the hypothalamic –pituitary–adrenal axis and hippocampal 5-hydroxytryptamine system, but also causes dysfunction of the central dopamine (DA) system and increases the susceptibility of dopaminergic neurons to pathogenic factors of Parkinson's disease (PD), for instance, 6-hydroxydopamine, thus impairing motor fu nction. We reviewed the impact of MS on the DA system and its correlation with PD and found t...
Source: NeuroMolecular Medicine - January 13, 2020 Category: Neurology Source Type: research

A Review of Functional Electrical Stimulation Treatment in Spinal Cord Injury
AbstractFunctional electrical stimulation (FES) has been widely adopted to elicit muscle contraction in rehabilitation training after spinal cord injury (SCI). Conventional FES modalities include stimulations coupled with rowing, cycling, assisted walking and other derivatives. In this review, we studied thirteen clinical reports from the past 5 years and evaluated the effects of various FES aided rehabilitation plans on the functional recovery after SCI, highlighting upper and lower extremity strength, cardiopulmonary function, and balder control. We further explored potential mechanisms of FES using the Hebbian theory an...
Source: NeuroMolecular Medicine - January 8, 2020 Category: Neurology Source Type: research

Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents
AbstractParkinson ’s disease (PD) is a neurodegenerative disease that is accompanied with the loss of dopaminergic neurons in the substantia nigra pars compacta which subsequently leads to a reduction in the dopamine level in the striatum. The flavonoids are gaining critical attention in the management of PD due to the toxic effects of the synthetic drugs. Naringin, a potent flavonoid, exerts neuroprotective activity against experimental animal models of PD. It also exhibits protective activity against rotenone-induced neurotoxicity in cell line studies. Therefore, the present study was designed to evaluate t he ther...
Source: NeuroMolecular Medicine - January 8, 2020 Category: Neurology Source Type: research

Ultrastructural Characteristics of DHA-Induced Pyroptosis
This study used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the morphological characteristics of pyroptosis in BV-2 microglial cells following exposure to 200  µM DHA. Vehicle-treated cells are characterized by extended processes, spine-like projections or 0.4 to 5.2 µm in length, and numerous extracellular vesicles (EVs) tethered to the surface of the plasma membrane. In contrast to vehicle-treated cells, gross abnormalities are observed after treati ng cells with 200 µM DHA for 4 h. These include the appearance of numerous pits or pore...
Source: NeuroMolecular Medicine - January 4, 2020 Category: Neurology Source Type: research

Mitochondrial DNA Copy Number in Peripheral Blood as a Potential Non-invasive Biomarker for Multiple Sclerosis
AbstractThe impaired mitochondrial function has been implicated in the pathogenicity of multiple sclerosis  (MS), a chronic inflammatory, demyelinating, and neurodegenerative disease of the CNS. Circulating mtDNA copy number in body fluids has been proposed as an indicator for several neurodegenerative diseases, and the altered cerebrospinal fluid mtDNA has been shown as a promising marker for MS. Th e aim of this study was to determine changes and biomarker potential of circulating mtDNA in peripheral blood in MS. The mtDNA copy number was quantified by real-time PCR in blood samples from 60 patients w...
Source: NeuroMolecular Medicine - January 4, 2020 Category: Neurology Source Type: research

Harpagophytum procumbens Extract Ameliorates Allodynia and Modulates Oxidative and Antioxidant Stress Pathways in a Rat Model of Spinal Cord Injury
AbstractSpinal cord injury (SCI) is  a deliberating disorder with impairments in locomotor deficits and incapacitating sensory abnormalities.Harpagophytum procumbens (Hp) is a botanical widely used for treating inflammation and pain related to various inflammatory and musculoskeletal conditions. Using a modified rodent contusion model of SCI, we explored the effects of this botanical on locomotor function and responses to mechanical stimuli, and examined possible neurochemical changes associated with SCI-induced allodynia. Following spinal cord contusion at T10 level, Hp (300  mg/kg, p.o.) or vehicle (water) was ...
Source: NeuroMolecular Medicine - January 3, 2020 Category: Neurology Source Type: research

O-GlcNAcylation as a Therapeutic Target for Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is the most common cause of dementia and the number of elderly patients suffering from AD has been steadily increasing. Despite worldwide efforts to cope with this disease, little progress has been achieved with regard to identification of effective therapeutics. Thus, active resea rch focusing on identification of new therapeutic targets of AD is ongoing. Among the new targets, post-translational modifications which modify the properties of mature proteins have gained attention. O-GlcNAcylation, a type of PTM that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) to a protein,...
Source: NeuroMolecular Medicine - January 1, 2020 Category: Neurology Source Type: research

A Transcriptomic Analysis of Neuropathic Pain in Rat Dorsal Root Ganglia Following Peripheral Nerve Injury
In this study, we screened the differentially expressed genes (DEGs) in the DRG from rats using RNA-seq technique. Moreover, the bioinformatics methods were used to figure out the signaling pathways and expression regulation pattern of the DEGs enriched in. In addition, quantitative real-time RT-PCR was carried out to further confirm the expression of DEGs. 414 genes were upregulated, while 184 genes were downregulated in the DRG of rats 7  days after partial sciatic nerve ligation (pSNL) surgery. Moreover, GO and KEGG enrichment analysis suggested that most of the altered genes were involved in inflammatory responses...
Source: NeuroMolecular Medicine - December 19, 2019 Category: Neurology Source Type: research

ACE-Triggered Hypertension Incites Stroke: Genetic, Molecular, and Therapeutic Aspects
AbstractStroke is the second largest cause of death worldwide. Angiotensin converting enzyme (ACE) gene has emerged as an important player in the pathogenesis of hypertension and consequently stroke. It encodes ACE enzyme that converts the inactive decapeptide angiotensin I to active octapeptide, angiotensin II (Ang II). Dysregulation in the expression of ACE gene, on account of genetic variants or regulation by miRNAs, alters the levels of ACE in the circulation. Variable expression of ACE affects the levels of Ang II. Ang II acts through different signal transduction pathways via various tyrosine kinases (receptor/non-re...
Source: NeuroMolecular Medicine - December 4, 2019 Category: Neurology Source Type: research

Scutellarin Exerts Anti-Inflammatory Effects in Activated Microglia/Brain Macrophage in Cerebral Ischemia and in Activated BV-2 Microglia Through Regulation of MAPKs Signaling Pathway
ConclusionsThe results suggest that scutellarin down-regulates the expression of proinflammatory mediators in AM/BM through suppressing the p-JNK and p-p38 MAPKs. Of note, the anti-inflammatory effect of p38 MAPK inhibitor and scutellarin is comparable. Besides, p38 MAPKs activator reverses the effect of scutellarin. Additionally, scutellarin increases p-ERK1/2 expression that may be neuroprotective. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - December 2, 2019 Category: Neurology Source Type: research

Topiramate Reverses Physiological and Behavioral Alterations by Postoperative Cognitive Dysfunction in Rat Model Through Inhibiting TNF Signaling Pathway
This study aimed to investigate the effects of topiramate (TPM) on rats with postoperative cognitive dysfunction (POCD) and elucidate the underlying mechanism. Differentially expressed genes in propofol-treated group and vehicle control group were filtered out and visualized in heatmap based on R program. POCD rat models were established for validation of TPM ’s anti-inflammatory action and Morris water maze (MWM) test was employed for assessment of spatial learning and memory ability of rats. Hematoxylin and eosin (HE) staining was applied to detect the neurodegeneration, and the apoptosis status was detected using ...
Source: NeuroMolecular Medicine - November 23, 2019 Category: Neurology Source Type: research

Stroke: Molecular Mechanisms and Therapies
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - November 19, 2019 Category: Neurology Source Type: research

Disregulation of Autophagy in the Transgenerational Cc2d1a Mouse Model of Autism
This study could help explain a new pathway of autophagy in ASD mouse models. Future animal studies need to investigate sex differences in mouse modeling autism-relevant genes likeCC2D1A. We anticipate our results to be a starting point for more comprehensive autophagy studies in this mouse model of ASD. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - November 13, 2019 Category: Neurology Source Type: research

Identification of PP2A and S6 Kinase as Modifiers of Leucine-Rich Repeat Kinase-Induced Neurotoxicity
AbstractMutations inLRRK2 are currently recognized as the most common monogenetic cause of Parkinsonism. The elevation of kinase activity of LRRK2 that frequently accompanies its mutations is widely thought to contribute to its toxicity. Accordingly, many groups have developed LRRK2-specific kinase inhibitors as a potential therapeutic strategy. Given that protein phosphorylation is a reversible event, we sought to elucidate the phosphatase(s) that can reverse LRRK2-mediated phosphorylation, with the view that targeting this phosphatase(s) may similarly be beneficial. Using an unbiased RNAi phosphatase screen conducted in ...
Source: NeuroMolecular Medicine - October 29, 2019 Category: Neurology Source Type: research

Dexmedetomidine Protects Against Oxygen –Glucose Deprivation-Induced Injury Through Inducing Astrocytes Autophagy via TSC2/mTOR Pathway
In conclusion, our study suggests that DEX exerts a neuroprotection against OGD-induced astrocytes injury via activation of astrocytes autophagy by regulating the TSC2/mTOR signaling pathway, which provides a new insight into the mechanisms of DEX treatment for acute ischemic injury. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - October 25, 2019 Category: Neurology Source Type: research

Association of HSPA1B Polymorphisms with Paranoid Schizophrenia in a Polish Population
This study aimed to find the potential association betweenHSPA1B polymorphisms and risk of paranoid schizophrenia, clinical variables of the disease, and suicidal behavior. A total of 901 unrelated Polish subjects of Caucasian origin (377 schizophrenia patients and 524 controls) were recruited. Four single-nucleotide polymorphisms (SNP) were genotyped using PCR –RFLP (rs539689, rs9281590) and TaqMan assays (rs263979, rs6547452). A strong tendency towards statistical significance (p = 0.051) was observed in rs539689 allele distribution between patients and controls in overall study subjects. After strati...
Source: NeuroMolecular Medicine - October 23, 2019 Category: Neurology Source Type: research

Is 1,8-Cineole-Rich Extract of Small Cardamom Seeds More Effective in Preventing Alzheimer ’s Disease than 1,8-Cineole Alone?
AbstractThe present study demonstrates the efficacies of synthetic 1,8-cineole and an 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in preventing oligomerization of amyloid beta peptide (A β42) and inhibiting iron-dependent oxyradical production in vitro. The oligomerization of Aβ42 was monitored by thioflavin T assay and MALDI-TOF analysis of the oligomers. The iron-dependent production of oxygen free radicals was detected by fluorometric benzoate hydroxylation assay. We observed t hat both pure 1,8-cineole and 1,8-cineole-rich extract of small cardamom seeds at concentra...
Source: NeuroMolecular Medicine - October 18, 2019 Category: Neurology Source Type: research

Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons
This study provides first evidence of neuroprotective potential of B-TCE against glutamate-induced excitotoxicity in hippocampus region and suggests that B-TCE may act as a potential candidate for neuroprotective therapeutic approaches. A single compound ‘tinosporicide’ was further isolated from B-TCE, which was found to be effective at 800× lower concentration against glutamate-induced neurodegeneration under in vitro conditions. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - October 12, 2019 Category: Neurology Source Type: research

Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics
AbstractOptogenetic stimulation of neural stem cells (NSCs) enables their activity-dependent photo-modulation. This provides a spatio-temporal tool for studying activity-dependent neurogenesis and for regulating the differentiation of the transplanted NSCs. Currently, this is mainly driven by viral transfection of channelrhodopsin-2 (ChR2) gene, which requires high irradiance and complex in vivo/vitro stimulation systems. Additionally, despite the extensive application of optogenetics in neuroscience, the transcriptome-level changes induced by optogenetic stimulation of NSCs have not been elucidated yet. Here, we made tran...
Source: NeuroMolecular Medicine - October 8, 2019 Category: Neurology Source Type: research

Variation in DNA Repair System Gene as an Additional Modifier of Age at Onset in Spinocerebellar Ataxia Type 3/Machado –Joseph Disease
AbstractSpinocerebellar ataxia type 3, or Machado –Joseph disease (SCA3/MJD), is caused by an expansion of CAG repeats, which is inversely correlated to age at onset (AO) of symptoms. However, on average, just 55.2% of variation in AO can be explained by expansion length. Additional modulators, such as polymorphic CAG tract inATXN2 gene, can raise to 63.0% of the variation in AO. A sequence variation (rs3512) inFAN1 gene has previously been shown to be associated with late AO in Huntington ’s disease and polyglutaminopathies associated to ataxia. In the present study, genotype frequency of rs3512 was demonstrat...
Source: NeuroMolecular Medicine - October 5, 2019 Category: Neurology Source Type: research

Cerebral Amyloid Angiopathy, Alzheimer ’s Disease and MicroRNA: miRNA as Diagnostic Biomarkers and Potential Therapeutic Targets
AbstractThe protein molecules must fold into unique conformations to acquire functional activity. Misfolding, aggregation, and deposition of proteins in diverse organs, the so-called “protein misfolding disorders (PMDs)”, represent the conformational diseases with highly ordered assemblies, including oligomers and fibrils that are linked to neurodegeneration in brain illnesses such as cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD). Recent studies have revea led several aspects of brain pathology in CAA and AD, but both the classification and underlying mechanisms need to be further refined...
Source: NeuroMolecular Medicine - October 4, 2019 Category: Neurology Source Type: research

Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells
AbstractMultiple sclerosis (MS) is a chronic autoimmune disease that degenerates the central nervous system (CNS). B cells exacerbate the progression of CNS lesions in MS by producing auto-antibodies, pro-inflammatory cytokines, and presenting auto-antigens to activated T cells. Long non-coding RNAs (lncRNAs) play a crucial role in complex biological processes and their stability in body fluids combined with their tissue specificity make these biomolecules promising biomarker candidates for MS diagnosis. In the current study, we investigated memory B cell-specific lncRNAs located, on average, less than 50  kb from dif...
Source: NeuroMolecular Medicine - October 1, 2019 Category: Neurology Source Type: research

Intravenous Immunoglobulin (IVIg) Induce a Protective Phenotype in Microglia Preventing Neuronal Cell Death in Ischaemic Stroke
AbstractTargeting the immune system and thereby modulating the inflammatory response in ischemic stroke has shown promising therapeutic potential in various preclinical trials. Among those, intravenous immunoglobulins (IVIg) have moved into the focus of attention. In a murine model of experimental stroke, we explored the therapeutic potential of IVIg on the neurological outcome and the inflammatory response. Further, we used an in vitro system to assess effects of IVIg-stimulated microglia on neuronal survival. Treatment with IVIg resulted in decreased lesion sizes, without significant effects on the infiltration and activ...
Source: NeuroMolecular Medicine - September 26, 2019 Category: Neurology Source Type: research

Acetyl-11-keto- β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion
AbstractBrain endothelial cells play an important role in maintaining blood flow homeostasis in the brain. Cerebral ischemia is a major cause of endothelial dysfunction which can disrupt the blood –brain barrier (BBB). Oxygen–glucose deprivation (OGD)/reperfusion promote cell death and BBB breakdown in brain endothelial cells. Acetyl-11-keto-β-boswellic acid (AKBA), a biologically active phytoconstituent of the medicinal plantBoswellia serrata, has been shown to be protective against various inflammatory diseases as well as ischemic brain injury. The molecular mechanisms underlying these beneficial charact...
Source: NeuroMolecular Medicine - September 12, 2019 Category: Neurology Source Type: research

Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets
AbstractDiabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, incidence of stroke in the presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrants the nee...
Source: NeuroMolecular Medicine - September 5, 2019 Category: Neurology Source Type: research

The Putative Association of TOB1 - AS1 Long Non-coding RNA with Immune Tolerance: A Study on Multiple Sclerosis Patients
In this study, 39 MS patients and 32 healthy matched controls were recruited. Real-time PCR  standard curve method was used to quantify transcript levels ofTOB1-AS1, TOB1, SKP2, andTSG. In addition, the potential sex hormone receptor binding sites on target genes promoter were analyzed using JASPR software. This work demonstrates a negative correlation betweenTOB1-AS1 expression and EDSS of patients. Also, a robust dysregulation of co-expression ofTOB1-AS1 lncRNA and the coding genes in MS patients compared to controls was observed. Such dysregulation in this pathway may be related to MS pathogenesis and response to i...
Source: NeuroMolecular Medicine - September 3, 2019 Category: Neurology Source Type: research

Prolactin is Not Associated with Disability and Clinical Forms in Patients with Multiple Sclerosis
AbstractAn association between prolactinemia with disability, clinical forms, and sex of patients with multiple sclerosis (MS) remains unclear. The aim of this study was to evaluate the association of prolactin with clinical forms and accumulating disability over time in patients with MS. A longitudinal study was carried out with 101 patients with relapsing –remitting MS (RRMS) and 19 with progressive forms of MS (ProgMS). The disability over time, as well as prolactin and ferritin serum levels were evaluated at baseline (T0), 8-month follow-up (T8), and 16-month follow-up. The disability at T0, T8, and T16 was highe...
Source: NeuroMolecular Medicine - August 31, 2019 Category: Neurology Source Type: research

Incidence and Clinical Features of TRPV4 -Linked Axonal Neuropathies in a USA Cohort of Charcot –Marie–Tooth Disease Type 2
In this study, we screened forTRPV4 mutations in a well-characterized USA cohort of 62 unrelated CMT2 patients without mutations inMFN2,GARS,NEFL, andGDAP1. All 15 coding exons ofTRPV4 were analyzed by Sanger-sequencing. Clinical features ofTRPV4-linked patients were compared with those lacking TRPV4 mutations. We identified twoTRPV4 mutations in two patients. A TRPV4-R316C was identified in a patient with family history, while a TRPV4-R269C in an apparently sporadic case. Marked clinical variations were observed in the patients withTRPV4 mutations. Our data suggest thatTRPV4-linked CMT2C accounts for a sizable fraction in...
Source: NeuroMolecular Medicine - August 29, 2019 Category: Neurology Source Type: research

CSF sAPP α and sAPPβ levels in Alzheimer’s Disease and Multiple Other Neurodegenerative Diseases: A Network Meta-Analysis
AbstractThe soluble amyloid protein procurer α (sAPPα) and β (sAPPβ) have been postulated as promising new cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) and multiple other neurodegenerative diseases, but have failed to meet expectations with their often discordant and even contradictory findings to date. The aim of th e study was to systematically explore this issue. Cochrane Library, PubMed, and CNKI were systematically searched without language or date restrictions. This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P...
Source: NeuroMolecular Medicine - August 14, 2019 Category: Neurology Source Type: research

C1 Esterase Inhibitor Reduces BBB Leakage and Apoptosis in the Hypoxic Developing Mouse Brain
AbstractInflammatory pathways involved in blood –brain barrier (BBB) vulnerability and hypoxic brain oedema in models of perinatal brain injury seem to provide putative therapeutic targets. To investigate impacts of C1-esterase inhibitor (C1-INH; 7.5–30 IU/kg, i.p.) on functional BBB properties in the hypoxic developing mouse brain (P7; 8% O2 for 6  h), expression of pro-apoptotic genes (BNIP3, DUSP1), inflammatory markers (IL-1ß, TNF-alpha, IL-6, MMP), and tight junction proteins (ZO-1, occludin, claudin-1, -5), and S100b protein concentrations were analysed after a regeneration period of 24&nb...
Source: NeuroMolecular Medicine - August 14, 2019 Category: Neurology Source Type: research

α-Arbutin Protects Against Parkinson’s Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo
AbstractParkinson ’s disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences sugges t that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted fromEric...
Source: NeuroMolecular Medicine - August 10, 2019 Category: Neurology Source Type: research

Mucopolysaccharidosis and Autophagy: Controversies on the Contribution of the Process to the Pathogenesis and Possible Therapeutic Applications
AbstractMucopolysaccharidosis (MPS) consists of a group of 11 enzymatic defects which result in accumulation of undegraded glycosaminoglycans (GAG) in lysosomes. MPS is a severe metabolic disease for which only bone marrow/hematopoietic stem cell transplantation and enzyme replacement therapy are current therapeutic options. However, they are available for only a few of MPS types, and are ineffective in treatment of central nervous system. Recent studies indicated that the autophagy process can be impaired in MPS, but various contradictory conclusions have been published in this matter. Nevertheless, stimulation of autopha...
Source: NeuroMolecular Medicine - August 1, 2019 Category: Neurology Source Type: research

RIP at the Synapse and the Role of Intracellular Domains in Neurons
AbstractRegulated intramembrane proteolysis (RIP) occurs in a cell when transmembrane proteins are cleaved by intramembrane proteases such as secretases to generate soluble protein fragments in the extracellular environment and the cytosol. In the cytosol, these soluble intracellular domains (ICDs) have local functions near the site of cleavage or in many cases, translocate to the nucleus to modulate gene expression. While the mechanism of RIP is relatively well studied, the fate and function of ICDs for most substrate proteins remain poorly characterized. In neurons, RIP occurs in various subcellular compartments includin...
Source: NeuroMolecular Medicine - July 25, 2019 Category: Neurology Source Type: research

Altered Hippocampal –Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse
AbstractFrontal infarcts can produce cognitive impairments that affect an individual ’s ability to function in everyday life. However, the precise types of deficits, and their underlying mechanisms, are not well-understood. Here we used a prefrontal photothrombotic stroke model in C57BL/6J mice to characterise specific cognitive changes that occur in the 6  weeks post-stroke. Behavioural experiments were paired with in vivo electrophysiology to assess whether changes in oscillatory communication between the prefrontal cortex (PFC) and the hippocampus (HPC) mirrored any observed behavioural changes. We found that...
Source: NeuroMolecular Medicine - July 16, 2019 Category: Neurology Source Type: research

Beneficial Effects of Fingolimod in Alzheimer ’s Disease: Molecular Mechanisms and Therapeutic Potential
AbstractAlzheimer ’s disease (AD), the most common cause of dementia remains of unclear etiology with current pharmacological therapies failing to halt disease progression. Several pathophysiological mechanisms have been implicated in AD pathogenesis including amyloid-β protein (Aβ) accumulation, tau hyperphospho rylation, neuroinflammation and alterations in bioactive lipid metabolism. Sphingolipids, such as sphingosine-1-phosphate (S1P) and intracellular ceramide/S1P balance are highly implicated in central nervous system physiology as well as in AD pathogenesis. FTY720/Fingolimod, a structural sphingosin...
Source: NeuroMolecular Medicine - July 16, 2019 Category: Neurology Source Type: research

Acid –Base and Electrolyte Changes Drive Early Pathology in Ischemic Stroke
AbstractEmergent large vessel occlusion accounts for 20 –40% of ischemic strokes and is the most debilitating form of stroke. Some of the earliest changes in response to ischemic stroke occur in blood gases and electrolytes. These biochemical changes occur within minutes after occlusion in experimental models of stroke and can be utilized to predict st roke outcomes. The majority of ELVO stroke patients are middle-aged to elderly and are of both sexes, revealing that there is an age and sex mismatch between ischemic stroke patients and animal models, since most experimental studies use young male rats. Rethinking of ...
Source: NeuroMolecular Medicine - July 6, 2019 Category: Neurology Source Type: research

Gastrodin Inhibits Inflammasome Through the STAT3 Signal Pathways in TNA2 Astrocytes and Reactive Astrocytes in Experimentally Induced Cerebral Ischemia in Rats
This study was aimed to determine Gastrodin (GAS) and its underlying signaling pathway involved in suppression of inflammasome specifically in reactive astrocytes that are featured prominently in different neurological conditions or diseases including cerebral ischemia. For this purpose, TNA2 astrocytes in cultures were exposed to oxygen –glucose–deprivation (OGD) mimicking hypoxic cerebral ischemia. Separately, TNA2 cells were pretreated with GAS prior to OGD exposure. Additionally, Stattic, an inhibitor of STAT3 signaling pathway, was used to ascertain its involvement in regulating inflammasome in astrocytes ...
Source: NeuroMolecular Medicine - June 19, 2019 Category: Neurology Source Type: research

Diabetic Stroke Promotes a Sexually Dimorphic Expansion of T Cells
AbstractWe recently reported that diabetes negates the cerebrovascular protection typically seen in adult female rats resulting in cognitive impairment, which is worsened by increased parenchymal bleeding and edema after ischemic stroke. Although women experience more severe diabetes and suffer from a higher rate of diabetic complications, including stroke and cognitive impairment, underlying mechanisms contributing to sex differences are limited. Emerging evidence suggests interleukin (IL)-17 contributes to cerebrovascular pathologies: (1) high salt diet-mediated expansion of IL-17-producing T cells (Th17) in the gut micr...
Source: NeuroMolecular Medicine - June 13, 2019 Category: Neurology Source Type: research

Sideroflexin 3 is a Mitochondrial Protein Enriched in Neurons
AbstractSideroflexin 1 (Sfxn1) is a mitochondrial serine transporter involved in one-carbon metabolism in blood and cancer cell lines. The expression of other Sfxn homologs varies across tissues implying that each homolog may have tissue-specific functions. RNA databases suggest that among the Sfxns, Sfxn3 may have a specific function in the brain. Here, we systematically analyzed the level, cellular distribution, and subcellular localization of Sfxn3 protein in the developing and adult rodent brain. We found that, in the cortex and hippocampus, Sfxn3 protein level is low at birth but increases during development and remai...
Source: NeuroMolecular Medicine - June 8, 2019 Category: Neurology Source Type: research

Measuring Respiration in Isolated Murine Brain Mitochondria: Implications for Mechanistic Stroke Studies
In conclusion, we provide detailed experimental design for measur ement of various respiratory parameters in isolated brain mitochondria utilizing a novel high-throughput technique along with interpretation and analysis of data. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 6, 2019 Category: Neurology Source Type: research

Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia
AbstractStroke significantly affects white matter in the brain by impairing axon function, which results in clinical deficits. Axonal mitochondria are highly dynamic and are transported via microtubules in the anterograde or retrograde direction, depending upon axonal energy demands. Recently, we reported that mitochondrial division inhibitor 1 (Mdivi-1) promotes axon function recovery by preventing mitochondrial fission only when applied during ischemia. Application of Mdivi-1 after injury failed to protect axon function. Interestingly, L-NIO, which is a NOS3 inhibitor, confers post-ischemic protection to axon function by...
Source: NeuroMolecular Medicine - May 31, 2019 Category: Neurology Source Type: research

Role of Apolipoprotein E, Cathepsin D, and Brain-Derived Neurotrophic Factor in Parkinson ’s Disease: A Study from Eastern India
This study suggests thatAPOE andBDNF may serve as modifier loci among eastern Indian PD patients. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - May 28, 2019 Category: Neurology Source Type: research

eIF2B Mutations Cause Mitochondrial Malfunction in Oligodendrocytes
AbstractVanishing white matter (VWM) disease (OMIM#306896) is an autosomal recessive neurodegenerative leukodystrophy caused by hypomorphic mutations in any of the five genes encoding the subunits of eukaryotic translation initiation factor 2B (eIF2B). The disease is manifested by loss of cerebral white matter and progressive deterioration upon exposure to environmental and physiological stressors. “Foamy” oligodendrocytes (OLG), increased numbers of oligodendrocytes precursor cells (OPC), and immature defective astrocytes are major neuropathological denominators. Our recent work using Eif2b5R132H/R132H mice un...
Source: NeuroMolecular Medicine - May 27, 2019 Category: Neurology Source Type: research

Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models
In conclusion, TBN ameliorated SAH-induced cerebral vasospasm and neuronal damage. These effects of TBN may be attributed to its anti-oxidative stress effect and up-regulation of Nrf2/HO-1. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - May 27, 2019 Category: Neurology Source Type: research

Blockade of Acid-Sensing Ion Channels Attenuates Recurrent Hypoglycemia-Induced Potentiation of Ischemic Brain Damage in Treated Diabetic Rats
AbstractDiabetes is a chronic metabolic disease and cerebral ischemia is a serious complication of diabetes. Anti-diabetic therapy mitigates this complication but increases the risk of exposure to recurrent hypoglycemia (RH). We showed previously that RH exposure increases ischemic brain damage in insulin-treated diabetic (ITD) rats. The present study evaluated the hypothesis that increased intra-ischemic acidosis in RH-exposed ITD rats leads to pronounced post-ischemic hypoperfusion via activation of acid-sensing (proton-gated) ion channels (ASICs). Streptozotocin-diabetic rats treated with insulin were considered ITD rat...
Source: NeuroMolecular Medicine - May 27, 2019 Category: Neurology Source Type: research

High-Mobility Group Box-1-Induced Angiogenesis After Indirect Bypass Surgery in a Chronic Cerebral Hypoperfusion Model
AbstractHigh-mobility group box-1 (HMGB1) is a nuclear protein that promotes inflammation during the acute phase post-stroke, and enhances angiogenesis during the delayed phase. Here, we evaluated whether indirect revascularization surgery with HMGB1 accelerates brain angiogenesis in a chronic cerebral hypoperfusion model. Seven days after hypoperfusion induction, encephalo-myo-synangiosis (EMS) was performed with or without HMGB1 treatment into the temporal muscle. We detected significant increments in cortical vasculature (p 
Source: NeuroMolecular Medicine - May 23, 2019 Category: Neurology Source Type: research

Long Noncoding RNAs in the Pathophysiology of Ischemic Stroke
AbstractIschemic stroke is an acute brain injury with high mortality and disability rates worldwide. The pathophysiological effects of ischemic stroke are driven by a multitude of complex molecular and cellular interactions that ultimately result in brain damage and neurological dysfunction. The Human Genome Project revealed that the vast majority of the human genome (and mammalian genome in general) is transcribed into noncoding RNAs. These RNAs have several important roles in the molecular biology of the cell. Of these, the long noncoding RNAs are gaining particular importance in stroke biology. High-throughput analysis ...
Source: NeuroMolecular Medicine - May 22, 2019 Category: Neurology Source Type: research

Influence of DRD1 and DRD3 Polymorphisms in the Occurrence of Motor Effects in Patients with Sporadic Parkinson ’s Disease
AbstractParkinson ’s disease (PD) is a multisystem disorder that affects 2–3% of the population ≥ 65 years of age. The main pharmacologic agent use in the treatment of clinical symptoms of PD is levodopa (L-DOPA). However, the chronic use of L-DOPA might result in the emergence of motor complications such as motor fluctuation and dyskinesia. Previous studies have shown that the inter-individual variability and pharmacogenetic profile of PD patients seem to influence the occurrence of motor complications. For these reasons, the purpose of this study was to evaluate a possible relationship betweenD...
Source: NeuroMolecular Medicine - May 22, 2019 Category: Neurology Source Type: research

Gut Microbiota Disorder, Gut Epithelial and Blood –Brain Barrier Dysfunctions in Etiopathogenesis of Dementia: Molecular Mechanisms and Signaling Pathways
AbstractEmerging evidences indicate a critical role of the gut microbiota in etiopathogenesis of dementia, a debilitating multifactorial disorder characterized by progressive deterioration of cognition and behavior that interferes with the social and professional functions of the sufferer. Available data suggest that gut microbiota disorder that triggers development of dementia is characterized by substantial reduction in specific species belonging to theFirmicutes andBacteroidetes phyla and presence of pathogenic species, predominantly, pro-inflammatory bacteria of theProteobacteria phylum. These changes in gut microbiota...
Source: NeuroMolecular Medicine - May 21, 2019 Category: Neurology Source Type: research