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Transcriptional Effects of ApoE4: Relevance to Alzheimer ’s Disease
AbstractThe major genetic risk factor for sporadic Alzheimer ’s disease (AD) is the lipid binding and transporting carrier protein apolipoprotein E, epsilon 4 allele (ApoE4). One of the unsolved mysteries of AD is how the presence of ApoE4 elicits this age-associated, currently incurable neurodegenerative disease. Recently, we showed that ApoE4 acts as a tr anscription factor and binds to the promoters of genes involved in a range of processes linked to aging and AD disease pathogenesis. These findings point to novel therapeutic strategies for AD and aging, resulting in an extension of human healthspan, the disease-f...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons
AbstractMesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson ’s disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditi oned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having ...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Inhibition of β-ARK1 Ameliorates Morphine-induced Tolerance and Hyperalgesia Via Modulating the Activity of Spinal NMDA Receptors
AbstractOur previous study has proposed that increased presynaptic NMDARs activities play pivotal roles in the development of opioid tolerance and hyperalgesia, and blocking spinal NMDARs attenuates chronic morphine-induced synaptic plasticity and behavior. However, the cellular signaling mechanisms remain to be investigated. The aim of this research was to address the role of β-ARK1 in opioid analgesia. Opioid tolerance and hyperalgesia was induced by daily systemic morphine injections in rats for eight consecutive days. Whole-cell voltage-clamp was employed to record spontaneous EPSCs and evoked-AMPA-EPSCs in dorsal...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Toxic Synergism Between Quinolinic Acid and Glutaric Acid in Neuronal Cells Is Mediated by Oxidative Stress: Insights to a New Toxic Model
In this study, the effects of subtoxic concentrations of QUIN and/or GA were tested in neuronal cultures, co-cultures (neuronal cells + astrocytes), and mixed cultures (neuronal cells + astrocytes + microglia) from rat cortex and striatum. The exposure of different cortical and striatal cell cultures to QUIN + GA resulted in cell death and stimulated different markers of oxidative stress, including reactive oxygen species (ROS) formation; changes in the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; and depletion of endogenous antioxidants such as -SH groups and glutathi...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

LINE-1 Hypermethylation in Serum Cell-Free DNA of Relapsing Remitting Multiple Sclerosis Patients
AbstractConcentrations of cell-free DNA (cfDNA) circulating in blood and its epigenetic variation, such as DNA methylation, may provide useful diagnostic or prognostic information. Long interspersed nuclear element-1 (LINE-1) constitutes approximately 20% of the human genome and its 5 ’UTR region is CpG rich. Due to its wide distribution, the methylation level of the 5’UTR of LINE-1 can serve as a surrogate marker of global genomic DNA methylation. The aim of the current study was to investigate whether the methylation status of LINE-1 elements in serum cell-free DNA differs between relapsing remitting multiple...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Cognitive Impairment and Brain and Peripheral Alterations in a Murine Model of Intraventricular Hemorrhage in the Preterm Newborn
AbstractGerminal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains a serious complication in the preterm newborn. The significant increase of survival rates in extremelye preterm newborns has also contributed to increase the absolute number of patients developing GMH-IVH. However, there are relatively few available animal models to understand the underlying mechanisms and peripheral markers or prognostic tools. In order to further characterize central complications and evolution of GMH-IVH, we injected collagenase intraventricularly to P7 CD1 mice and assessed them in the short (P14) and the long term (P70). ...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Angiotensin Receptor Blockade by Inhibiting Glial Activation Promotes Hippocampal Neurogenesis Via Activation of Wnt/ β-Catenin Signaling in Hypertension
AbstractHypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer ’s disease (AD). On the other hand, CNS diseases like AD have been associated with gliosis and impaired neurogenesis. Further, renin angiotensin system (RAS) is intricately associated with hypertension; however, the accumulating evidences suggest that over-activity of RAS may perpetuate the brain inflammation related with AD. Therefore, in the present study, we examined the effect of hypertension and RAS on glial (astrocytes and microglia) activation and hippocampal neurogenesis in a rat model of...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Vitamin B 6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation
AbstractNeurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250 –300 g) were submitted to cecal ligatio...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

6-OHDA Induces Oxidation of F-box Protein Fbw7 β by Chaperone-Mediated Autophagy in Parkinson’s Model
In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanism s. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals’ models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated a utophagy (CMA), at a higher affinity. Oxidative stress also increased the level of lysosomal-associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate flux, and s...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Loss of Pericytes in Radiation Necrosis after Glioblastoma Treatments
In this study, we showed that the loss of pericytes is involved in the pathogenesis of RN. From a brain tumor tissue repository, we identified three patients since 2011 with pathologically confirmed RN after the standard treatment for glioblastoma (GBM). The RN and their preradiation GBM tissues were serially processed for Western blotting using cell-type-specific antibodies against endothelial (CD31, active RhoA), pericyte [platelet-derived growth factor receptor-beta (PDGFR- β)], alpha-smooth muscle actin (α-SMA), astrocyte (GFAP), myelin sheath protein (MBP), and microglial markers (Iba1). Normal brain tissue...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Glutamate-Dependent Translational Control of Glutamine Synthetase in Bergmann Glia Cells
AbstractGlutamate is the major excitatory transmitter of the vertebrate brain. It exerts its actions through the activation of specific plasma membrane receptors expressed both in neurons and in glial cells. Recent evidence has shown that glutamate uptake systems, particularly enriched in glia cells, trigger biochemical cascades in a similar fashion as receptors. A tight regulation of glutamate extracellular levels prevents neuronal overstimulation and cell death, and it is critically involved in glutamate turnover. Glial glutamate transporters are responsible of the majority of the brain glutamate uptake activity. Once in...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

MicroRNA Profiling in Aging Brain of PSEN1/PSEN2 Double Knockout Mice
AbstractMicroRNAs are small non-coding RNAs that function as regulators of gene expression. The altered expression of microRNAs influences the pathogenesis of Alzheimer ’s disease. Many researchers have focused on studies based on the relatively distinctive etiology of familial Alzheimer’s disease due to the absence of risk factors in the pathogenesis of sporadic Alzheimer’s disease. Although there is a limitation in Alzheimer’s disease studies, both Alzhei mer’s disease types have a common risk factor—aging. No study to date has examined the aging factor in Alzheimer’s disease ani...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

A Missense Variant p.Ala117Ser in the Transthyretin Gene of a Han Chinese Family with Familial Amyloid Polyneuropathy
This study aims to explore the genetic features of a Han Chinese family with FAP, characterized by bloating, alternating diarrhea and constipation, and weakness in his feet. Amyloid presented histologically in the vessel walls of hepatic portal area and nerves of the surgically excised liver specimens from the proband by hematoxylin and eosin staining. Amyloid deposition was further confirmed with Congo red treatment. A c.349G>T transversion (p.Ala117Ser) inTTR gene exon 4 was identified in the proband with typical autonomic neuropathy and peripheral motor neuropathy, as well as in his asymptomatic son. The variant was ...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Antipsychotic-Like Efficacy of Dopamine D 2 Receptor-Biased Ligands is Dependent on Adenosine A 2A Receptor Expression
AbstractDopamine D2 receptor (D2R) activation triggers both G protein- and β-arrestin-dependent signaling. Biased D2R ligands activating β-arrestin pathway have been proposed as potential antipsychotics. The ability of D2R to heteromerize with adenosine A2A receptor (A2AR) has been associated to D2R agonist-induced β-arrestin recruitment. Accordingly, here we aimed to demonstrate the A2AR dependence of D2R/ β-arrestin signaling. By combining bioluminescence resonance energy transfer (BRET) between β-arrestin-2 tagged with yellow fluorescent protein and bimolecular luminescence complementation (BiLC...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Sulforaphane Promotes Mitochondrial Protection in SH-SY5Y Cells Exposed to Hydrogen Peroxide by an Nrf2-Dependent Mechanism
AbstractSulforaphane (SFN; C6H11NOS2) is an isothiocyanate found in cruciferous vegetables, such as broccoli, kale, and radish. SFN exhibits antioxidant, anti-apoptotic, anti-tumor, and anti-inflammatory activities in different cell types. However, it was not previously demonstrated whether and how this natural compound would exert mitochondrial protection experimentally. Therefore, we investigated here the effects of a pretreatment (for 30  min) with SFN at 5 μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) at 300  μM for 24 h. We found that S...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Cells Expressing Prominin-1 in Neonatal Murine Inferior Colliculus Differentiate into Neurons and Glia
AbstractInferior colliculus (IC) is a major center for the integration and processing of acoustic information from ascending auditory pathways. Damage to the IC as well as normal aging can impair auditory function. Novel strategies such as stem cell (SC)-based regenerative therapy are required for functional recovery because mature neural cells have a minimal regenerative capacity after an injury. However, it is not known if there are neural stem cells (NSCs) in the IC. Herein, we screened for NSCs by surface marker analysis using flow cytometry. Isolated IC cells expressing prominin-1 (CD133) exhibited the cardinal NSC pr...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Erratum to: Loss of Pericytes in Radiation Necrosis after Glioblastoma Treatments
(Source: Molecular Neurobiology)
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Taurine Protects from Pentylenetetrazole-Induced Behavioral and Neurochemical Changes in Zebrafish
AbstractEpilepsy is a common neurological disorder characterized by recurrent unprovoked seizures, which culminate in various neurobehavioral and neurochemical changes. Taurine (TAU) is an amino sulfonic acid which acts an endogenous inhibitory neuromodulator. Moreover, TAU displays intrinsic antioxidant activity, contributing to its beneficial actions in the CNS. Here, we evaluated whether TAU pretreatment protects from pentylenetetrazole (PTZ)-induced behavioral alterations and oxidative stress-related parameters in zebrafish brain tissue. Fish were pretreated with 42, 150, and 400  mg/L TAU (40 min) and furthe...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Zbtb20 Regulates Developmental Neurogenesis in the Olfactory Bulb and Gliogenesis After Adult Brain Injury
AbstractThe transcription factor (TF) Zbtb20 is important for the hippocampal specification and the regulation of neurogenesis of neocortical projection neurons. Herein, we show a critical involvement of the  TFZbtb20 in the neurogenesis of both projection neurons and interneurons of the olfactory bulb during embryonic stages. Our data indicate that the lack of Zbtb20 significantly diminishes the generation of a set of early-born Tbr2+ neurons during embryogenesis. Furthermore, we provide evidence thatZbtb20 regulates the transition between neurogenesis to gliogenesis in cortical radial glial progenitor cells at the p...
Source: Molecular Neurobiology - May 11, 2018 Category: Neurology Source Type: research

Targeting β-Catenin in GLAST-Expressing Cells: Impact on Anxiety and Depression-Related Behavior and Hippocampal Proliferation
Abstractβ-catenin (key mediator in the Wnt signaling pathway) contributes to the pathophysiology of mood disorders, associated to neurogenesis and neuroplasticity. Decreased β-catenin protein levels have been observed in the hippocampus and prefrontal cortex of depressed subjects. Additionally, the antide pressants exert, at least in part, their neurogenic effects by increasing β-catenin levels in the subgranular zone of the hippocampus. To further understand the role of β-catenin in depression and anxiety, we generated two conditional transgenic mice in which β-catenin was either inactivated or s ...
Source: Molecular Neurobiology - May 8, 2018 Category: Neurology Source Type: research

The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS 1 Activation
AbstractBasal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer ’s disease (AD), which has been suggested to be “Type 3 Diabetes.” We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 mon ths old 3×Tg-AD mice, reported to de...
Source: Molecular Neurobiology - May 7, 2018 Category: Neurology Source Type: research

Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin
AbstractCalsenilin is a calcium ion (Ca2+)-binding protein involved in regulating the intracellular concentration of Ca2+, a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca2+ signals entering the cytoplasm by releasing Ca2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein...
Source: Molecular Neurobiology - May 5, 2018 Category: Neurology Source Type: research

Omega-3 Fatty Acids Attenuate Brain Alterations in High-Fat Diet-Induced Obesity Model
This study evaluated the effects of omega-3 on inflammation, oxidative stress, and energy metabolism parameters in the brain of mice subjected to high-fat diet-induced obesity model. Body weight and visceral fat weight were evaluated as well. Male Swiss mice were divided into control (purified low-fat diet) and obese (purified high-fat diet). After 6  weeks, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + OMEGA-3. Fish oil (400 mg/kg/day) or saline solution was administrated orally, during 4 weeks. When the experiment completed 10 weeks, the animals were eut...
Source: Molecular Neurobiology - May 4, 2018 Category: Neurology Source Type: research

JM-20 Treatment After MCAO Reduced Astrocyte Reactivity and Neuronal Death on Peri-infarct Regions of the Rat Brain
In this study, we look into plausible molecular and cellular targets for JM-20, a new hybrid molecule, against ischemic stroke in vivo. Male Wistar rats were subjected to 90  min middle cerebral artery occlusion (MCAO) following 23 h of reperfusion. Animals treated with 8 mg/kg JM-20 (p.o., 1 h after reperfusion) showed minimal neurological impairment and lower GABA and IL-1β levels in CSF when compared to damaged rats that received vehicle. Immunocontent of pro-su rvival, phosphorylated Akt protein decreased in the cortex after 24 h as result of the ischemic insult, accompanied by decreased n...
Source: Molecular Neurobiology - May 3, 2018 Category: Neurology Source Type: research

Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats
AbstractImmune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs. The expression of elements of the IDO...
Source: Molecular Neurobiology - May 3, 2018 Category: Neurology Source Type: research

Id1 and Sonic Hedgehog Mediate Cell Cycle Reentry and Apoptosis Induced by Amyloid Beta-Peptide in Post-mitotic Cortical Neurons
AbstractAmyloid beta-peptide (A β), the neurotoxic component of senile plaques in Alzheimer’s disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aβs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al.,Mol Neurobiol 53(2):793 –809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aβ-induced Id1 and SHH contribute to cell cycle reentry l...
Source: Molecular Neurobiology - May 2, 2018 Category: Neurology Source Type: research

Abscisic Acid Supplementation Rescues High Fat Diet-Induced Alterations in Hippocampal Inflammation and IRSs Expression
In conclusion, this study highlights different regulations of hippocampal IRS1 and IRS2 expression using a HFD, indicating the important differences of these scaffolding proteins, and strongly supports ABA therapeutic effects . (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - May 2, 2018 Category: Neurology Source Type: research

Endothelin-1 Decreases Excitability of the Dorsal Root Ganglion Neurons via ET B Receptor
In conclusion, our results demonstrate that ET-1 hyperpolarizes nociceptors by blockingINa and potentiatingIKT through selective activation of ETBR, which may represent one of the underlying mechanisms for reported anti-nociceptive effects of ET-1. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

The Lesion Analysis of Cholinergic Neurons in 5XFAD Mouse Model in the Three-Dimensional Level of Whole Brain
AbstractCholinergic system is very important for many higher brain functions, including learning and memory. Cholinergic neurons, especially those in the basal forebrain, are specifically susceptible in some neurodegenerative diseases, such as in Alzheimer ’s disease (AD). Here, we studied the cholinergic system lesion effects of five familial AD mutations in 5XFAD mice, a transgenic mouse model of AD. Although the cholinergic system has been studied in this mouse model, the cholinergic deficits in AD mice have never been systematically mapped in a whole-brain three-dimensional (3D) reconstruction. Using the 3D recon...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway
AbstractRepetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment. We found that high-frequency rTMS ...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells
AbstractDifferentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor ge...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions
AbstractZika virus (ZIKV) is an emerging arbovirus of the genus Flaviviridae, which causes a febrile illness and has spread from across the Pacific to the Americas in a short timeframe. Convincing evidence has implicated the ZIKV to incident cases of neonatal microcephaly and a set of neurodevelopmental abnormalities referred to as the congenital Zika virus syndrome. In addition, emerging data points to an association with the ZIKV and the development of the so-called Guillain-Barre syndrome, an acute autoimmune polyneuropathy. Accumulating knowledge suggests that neurovirulent strains of the ZIKV have evolved from less pa...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Suppression of TLR4/NF- κB Signaling Pathway Improves Cerebral Ischemia–Reperfusion Injury in Rats
AbstractThe present study aimed to investigate the effects of the toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF- ҡB) signaling pathway in cerebral ischemia–reperfusion injury. A total of 125 male Sprague Dawley (SD) rats were selected for this study. Fifty SD rats were randomly divided into the control, sham injury, 0.5 h perfusion, 2 h perfusion, and 6 h perfusion groups to establish the model of ischem ia–reperfusion. The rat brain injury model was established using the other 75 male SD rats, and different model groups with different treatments were established (15 rats per group): mod...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

TRPV4 Activation Contributes Functional Recovery from Ischemic Stroke via Angiogenesis and Neurogenesis
In this study, we first tested whether TRPV4 activation can improve functional recovery in rats subjected to transient brain ischemia. The possible mechanisms for TRPV4 activation-promoted functional recovery were explored. A TRPV4 agonist, 4 α-phorbol 12,13-didecanoate (4α-PDD), was intravenously injected via the tail vein at 6 h and 1, 2, 3, 4 days after ischemic stroke. The treatment reduced infarct volume by almost 50% (14.7 ± 3.7 vs. 29.2 ± 6.2%;p 
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Long-Term Plasticity in Amygdala Circuits: Implication of CB1-Dependent LTD in Stress
AbstractThe amygdala mediates many forms of emotional learning, during which the central nucleus of amygdala (CeA) functions as a major output of the amygdala by converging inputs from the basolateral nucleus (BLA) and other amygdalar subregions. However, the contribution of BLA-CeA synaptic transmission and plasticity of this transmission after exposure to emotional stimuli remains to be completely understood. Using paired recording, we simultaneously recorded BLA and CeA neurons, and observed that BLA-CeA transmission was glutamatergic. In this transmission, high-frequency stimulation induced NMDA receptor (NMDAR)-depend...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Weakened Intracellular Zn 2+ -Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP
AbstractMemory is lost by the increased influx of extracellular Zn2+ into neurons. It is possible that intracellular Zn2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn2+ dynamics was compared between young and aged rats. The influx of extracellular Zn2+ into dentate granule cells was increased in aged rats after inje...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Neuroprotective Benefits of Aerobic Exercise and Organoselenium Dietary Supplementation in Hippocampus of Old Rats
This study suggests that physical exercise and a diet supplemented with (PhSe)2 promoted neuroprotection in the hippocampus of aged rats. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain
In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain. The chronic alcohol consumption enhanced plantar incision-produced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 phosphorylation at the Ser831 site in the spinal cord. The targeted mutation of the GluA1 phosphorylation site in GluA1 S831A mutant mice significantly inhibited the incisional pain prolongation produced by chronic alcohol c onsumpti...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Apoptosis Following Cortical Spreading Depression in Juvenile Rats
AbstractRepetitive cortical spreading depression (CSD) can lead to cell death in immature brain tissue. Caspases are involved in neuronal cell death in several CSD-related neurological disorders, such as stroke and epilepsy. Yet, whether repetitive CSD itself can induce caspase activation in adult or juvenile tissue remains unknown. Inducing repetitive CSD in somatosensory cortices of juvenile and adult rats in vivo, we thus aimed to investigate the effect of repetitive CSD on the expression caspase-3, caspase-8, caspase-9, and caspase-12 in different brain regions using immunohistochemistry and western blotting techniques...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons
AbstractMitochondria are widely recognized as fundamental organelles for cellular physiology and constitute the main energy source for different cellular processes. The location, morphology, and interactions of mitochondria with other organelles, such as the endoplasmic reticulum (ER), have emerged as critical events capable of determining cellular fate. Mitochondria-related functions have proven particularly relevant in neurons; mitochondria are necessary for proper neuronal morphogenesis and the highly energy-demanding synaptic transmission process. Mitochondrial health depends on balanced fusion-fission events, termed m...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Adenosine Augmentation Evoked by an ENT1 Inhibitor Improves Memory Impairment and Neuronal Plasticity in the APP/PS1 Mouse Model of Alzheimer ’s Disease
In conclusion, our findings suggest that modulation of adenosine homeostasis by J4 is beneficial in a mouse model of AD. Our study provides a potential therapeutic strategy to delay the progression of AD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

7-Deoxy-trans-dihydronarciclasine Reduces β-Amyloid and Ameliorates Memory Impairment in a Transgenic Model of Alzheimer’s Disease
AbstractThe critical pathological feature of Alzheimer ’s disease (AD) is the accumulation of β-amyloid (Aβ), the main constituent of amyloid plaques. β-amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretase generating Aβ at endosomes or non-amyloidogenic processing by α-secretase precluding the production of Aβ at the plasma membrane. Recently, several natural products have been widely researched on the prevention of Aβ accumulation for AD treatment. We previously reported thatLycoris chejuensis K. Tae et S. Ko (CJ), which originated from...
Source: Molecular Neurobiology - April 4, 2018 Category: Neurology Source Type: research

Evidence for Compromised Insulin Signaling and Neuronal Vulnerability in Experimental Model of Sporadic Alzheimer ’s Disease
AbstractEvidence from animal studies categorizes sporadic Alzheimer ’s disease (sAD) as a metabolic syndrome with accompanying cognitive deficits. Given that glial cells act as “silent partners” to neurons by providing trophic support and defense, the present study investigated the role of glia in sAD pathology. A streptozotocin (STZ)-induced glial-neuronal co -culture model of sAD was used to study the metabolic status of the two cell types. Real time RT-PCR and Western blotting results indicated that amyloid precursor protein (APP) and β-secretase (BACE1) were highly expressed in co-cultured n...
Source: Molecular Neurobiology - April 3, 2018 Category: Neurology Source Type: research

The Compensatory Immune-Regulatory Reflex System (CIRS) in Depression and Bipolar Disorder
AbstractHere, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors. These immune aberrations appear to be evident during the course of major affecti...
Source: Molecular Neurobiology - April 2, 2018 Category: Neurology Source Type: research

11 β-HSD1 Inhibition by RL-118 Promotes Autophagy and Correlates with Reduced Oxidative Stress and Inflammation, Enhancing Cognitive Performance in SAMP8 Mouse Model
AbstractElevated glucocorticoid (GC) exposure is widely accepted as a key factor in the age-related cognitive decline in rodents and humans. 11 β-HSD1 is a key enzyme in the GCs pathway, catalyzing the conversion of 11β-dehydrocorticosterone to corticosterone in mice, with possible implications in neurodegenerative processes and cognitive impairment. Here, we determined the effect of a new 11β-HSD1 inhibitor, RL-118, administered to 12-m onth-old senescence-accelerated mouse-prone 8 (SAMP8) mice with neuropathological AD-like hallmarks and widely used as a rodent model of cognitive dysfunction. Behavioral te...
Source: Molecular Neurobiology - April 2, 2018 Category: Neurology Source Type: research

Resveratrol Acts Anti-Inflammatory and Neuroprotective in an Infant Rat Model of Pneumococcal Meningitis by Modulating the Hippocampal miRNome
AbstractResveratrol (RSV) is anti-inflammatory and neuroprotective, cross the blood –brain barrier (BBB) and has a safe profile. Besides, RSV modulates the expression of some miRNAs related to neurological disorders. Thus, we hypothesized that RSV can be neuroprotective in pneumococcal meningitis by modulating the global microRNA expression profile (miRNome). Eleven-day old rats were intracysternally infected withS. pneumoniae (~  2 × 106 c.f.u.) and were orally administered with RSV (50  mg/kg) or vehicle in pre-treatment (before infection) or post-treatment schedules (3 and 18 h...
Source: Molecular Neurobiology - April 2, 2018 Category: Neurology Source Type: research

Correction to: The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against α-Synuclein-Induced Toxicity
AbstractWith the author(s) ’ decision to opt for Open Choice the copyright of the article changed on March 2018 to © The Author(s) 2018 and the name of one of the author was changed to “Sanjib Guha”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - April 2, 2018 Category: Neurology Source Type: research

PKA-GSK3 β and β-Catenin Signaling Play a Critical Role in Trans -Resveratrol Mediated Neuronal Differentiation in Human Cord Blood Stem Cells
AbstractThe role of resveratrol (RV), a natural polyphenol, is well documented, although its role on neurogenesis is still controversial and poorly understood. Therefore, to decipher the cellular insights of RV on neurogenesis, we investigated the potential effects of the compound on the survival, proliferation, and neuronal differentiation of human cord blood-derived mesenchymal stem cells (hCBMSCs). For neuronal differentiation, purified and characterized hCBMSCs were exposed to biological safe doses of RV (10  μM) alone and in combination with nerve growth factor (NGF-50 ng). The cells exposed only to NGF (...
Source: Molecular Neurobiology - March 8, 2018 Category: Neurology Source Type: research

Genetic Mutation of GluN2B Protects Brain Cells Against Stroke Damages
AbstractImmediately following ischemia, glutamate accumulates in the extracellular space and results in extensive stimulation of its receptors including N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. A large amount of Ca2+ influx directly through the receptor-gated ion channels which leads to Ca2+ overload and triggers several downstream lethal reactions. As a result, cell dies via apoptosis or necrosis, or both. Death-associated protein kinase 1 (DAPK1) physically and functionally interacts with the NMDA receptor GluN2B subunit at extra-synaptic sites and this...
Source: Molecular Neurobiology - March 8, 2018 Category: Neurology Source Type: research

Attenuation of Glutamate-Induced Excitotoxicity by Withanolide-A in Neuron-Like Cells: Role for PI3K/Akt/MAPK Signaling Pathway
AbstractGlutamate-induced excitotoxicity is one of the major underlying mechanisms for neurodegenerative diseases. Efforts are being made to treat such conditions with an array of natural compounds that can modulate the release of glutamate or the underlying mechanisms associated with it.Withania somnifera extract has potent pharmacologic activity similar to that of Korean Ginseng tea and is used to treat several neuronal disorders. However, to date, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to investigate withanolide-A, on...
Source: Molecular Neurobiology - March 8, 2018 Category: Neurology Source Type: research