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Source: Molecular Neurobiology
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Total 278 results found since Jan 2013.
Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis
In this study, we used fluid percussion injury in rats to simulate mild TBI. For rats, we used both passive avoidance learning and the Y-maze tests to evaluate cognitive function. We investigated whether PE rehabilitation attenuated cognitive deficits in rats with TBI and determined the contribution of hippocampal and cortical expression of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery. In addition to increasing hippocampal and cortical expression of HSP20, brain-derived neurotrophic factor (BDNF), and the tropomyosin receptor kinase B (TrkB) ratio, PE rehabilitation significantly attenuated brain contusi...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
Folic Acid Exerts Post-Ischemic Neuroprotection In Vitro Through HIF-1 α Stabilization
AbstractThe constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research
miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells
AbstractEndothelial dysfunction is a key element in cerebral small vessel disease (CSVD), which may cause stroke and cognitive decline. Cyclic nucleotide signaling modulates endothelial function. The cyclic adenosine monophosphate-degrading enzyme phosphodiesterase 3 (PDE3) is an important treatment target which may be modulated by microRNAs (miRNAs) important for regulating gene expression. We aimed to identify PDE3-targeting miRNAs to highlight potential therapeutic targets for endothelial dysfunction and CSVD. PDE3-targeting miRNAs were identified by in silico analysis (TargetScan, miRWalk, miRanda, and RNA22). The iden...
Source: Molecular Neurobiology - January 2, 2019 Category: Neurology Source Type: research
Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death
AbstractNR4A2 is a nuclear receptor and a transcription factor, with distinctive physiological features. In the cell nuclei of the central nervous system, it is widely expressed and identified as a crucial regulator of dopaminergic (DA) neuronal differentiation, survival, and maintenance. Importantly, it has regulated different genes crucial for dopaminergic signals, and its expression has been diminished in both aged and PD post-mortem brains and reduced in PD patients. In microglia and astrocytes, the expression of NR4A2 has been found where it can be capable of inhibiting the expression of proinflammatory mediators; hen...
Source: Molecular Neurobiology - January 25, 2019 Category: Neurology Source Type: research
Sphingosine 1-Phosphate Signaling Is Involved in Impaired Blood –Brain Barrier Function in Ischemia–Reperfusion Injury
AbstractSphingosine 1-phosphate (S1P) is a major bioactive lipid mediator in the vascular and immune system. Here, we have shown that inhibition of S1P signaling prevents blood –brain barrier (BBB) dysfunction after ischemia both in vitro and in vivo. In the in vitro BBB models, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of an S1P synthesizing enzyme (Sphk1) and S1P transporters (Abca1, Spns2), increasing S1P in culture media. Inhibitors of Sphk1 (SKI-II) or Abca1 (probucol) attenuated the decrease in transendothelial electrical resistance and the increase in permeability caused by OGD/R...
Source: Molecular Neurobiology - December 3, 2019 Category: Neurology Source Type: research
Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina
AbstractThe retina is an extension of the central nervous system and has been considered to be a simplified, more tractable and accessible version of the brain for a variety of neuroscience investigations. The optic nerve displays changes in response to underlying neurodegenerative diseases, such as stroke, multiple sclerosis, and Alzheimer ’s disease, as well as inner retinal neurodegenerative disease, e.g., glaucoma. Neurodegeneration has increasingly been linked to dysfunctional energy metabolism or conditions in which the energy supply does not meet the demand. Likewise, increasing lactate levels have been correlated...
Source: Molecular Neurobiology - January 7, 2020 Category: Neurology Source Type: research
NLRP3 Depletion Fails to Mitigate Inflammation but Restores Diminished Phagocytosis in BV-2 Cells After In Vitro Hypoxia
AbstractPost-hypoxic/ischemic neuroinflammation is selectively driven by sterile inflammation, which implies the interplay of brain-intrinsic immune cells with other neural cells and immigrated peripheral immune cells. The resultant inflammatory cascade evolves extra- and intracellular pathogen and danger-associated receptors. The latter interacts with multiprotein complexes termed inflammasomes. The NLRP3 inflammasome is one of the best-described inflammasomes. However, its impact on post-ischemic neuroinflammation and its role in neuroprotection after ischemic stroke are still under debate. Microglial cells are known to ...
Source: Molecular Neurobiology - March 31, 2020 Category: Neurology Source Type: research
cGAS/STING Pathway Activation Contributes to Delayed Neurodegeneration in Neonatal Hypoxia-Ischemia Rat Model: Possible Involvement of LINE-1
AbstractcGAS is a sensor of cytosolic DNA and responds equally to exogenous and endogenous DNA. After recognition of cytosolic dsDNA or ssDNA, cGAS synthesizes the second messenger 2 ′3′-cGAMP, which then binds to and activates stimulator of interferon genes (STING). STING plays an essential role in responding to pathogenic DNA and self-DNA in the context of autoimmunity. In pathologic conditions, such as stroke or hypoxia-ischemia (HI), DNA can gain access into the cytoplas m of the cell and leak from the dying cells into the extracellular environment, which potentially activates cGAS/STING. Recent in vivo studies of ...
Source: Molecular Neurobiology - April 5, 2020 Category: Neurology Source Type: research
Loss of Estrogen Efficacy Against Hippocampus Damage in Long-Term OVX Mice Is Related to the Reduction of Hippocampus Local Estrogen Production and Estrogen Receptor Degradation
AbstractPostmenopausal women experience a higher risk for neurodegenerative diseases, including cognitive impairment and ischemic stroke. Many preclinical studies have indicated that estrogen replacement therapy (ERT) may provide protective effects against these neurological diseases. However, the results of Women ’s Health Initiative (WHI) studies have led to the proposal of “critical period hypothesis,” which states that there is a precise window of opportunity for administering beneficial hormone therapy following menopause. However, the underlying molecular mechanisms require further characterizatio n. Here, we e...
Source: Molecular Neurobiology - June 14, 2020 Category: Neurology Source Type: research
Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival
AbstractThe cytolytic protein perforin has a crucial role in infections and tumor surveillance. Recently, it has also been associated with many brain diseases, such as neurodegenerative diseases and stroke. Therefore, inhibitors of perforin have attracted interest as novel drug candidates. We have previously reported that converting a perforin inhibitor into an L-type amino acid transporter 1 (LAT1)-utilizing prodrug can improve the compound ’s brain drug delivery not only across the blood–brain barrier (BBB) but also into the brain parenchymal cells: neurons, astrocytes, and microglia. The present study evaluated whet...
Source: Molecular Neurobiology - September 24, 2020 Category: Neurology Source Type: research
Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway
AbstractOxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementati...
Source: Molecular Neurobiology - October 7, 2020 Category: Neurology Source Type: research
Adenosine Signaling and Clathrin-Mediated Endocytosis of Glutamate AMPA Receptors in Delayed Hypoxic Injury in Rat Hippocampus: Role of Casein Kinase 2
AbstractChronic adenosine A1R stimulation in hypoxia leads to persistent hippocampal synaptic depression, while unopposed adenosine A2AR receptor stimulation during hypoxia/reperfusion triggers adenosine-induced post-hypoxia synaptic potentiation (APSP) and increased neuronal death. Still, the mechanisms responsible for this adenosine-mediated neuronal damage following hypoxia need to be fully elucidated. We tested the hypothesis that A1R and A2AR regulation by protein kinase casein kinase 2 (CK2) and clathrin-dependent endocytosis of AMPARs both contribute to APSPs and neuronal damage. The APSPs following a 20-min hypoxia...
Source: Molecular Neurobiology - January 7, 2021 Category: Neurology Source Type: research
Multiple Neuroinvasive Pathways in COVID-19
AbstractCOVID-19 is a highly infectious viral disease caused by the novel coronavirus SARS-CoV-2. While it was initially regarded as a strictly respiratory illness, the impact of COVID-19 on multiple organs is increasingly recognized. The brain is among the targets of COVID-19, and it can be impacted in multiple ways, both directly and indirectly. Direct brain infection by SARS-CoV-2 may occur via axonal transport via the olfactory nerve, eventually infecting the olfactory cortex and other structures in the temporal lobe, and potentially the brain stem. A hematogenous route, which involves viral crossing of blood –brain ...
Source: Molecular Neurobiology - January 28, 2021 Category: Neurology Source Type: research
The Expanding Regulatory Mechanisms and Cellular Functions of Long Non-coding RNAs (lncRNAs) in Neuroinflammation
AbstractLncRNAs have emerged as important regulatory molecules in biological processes. They serve as regulators of gene expression pathways through interactions with proteins, RNA, and DNA. LncRNA expression is altered in several diseases of the central nervous system (CNS), such as neurodegenerative disorders, stroke, trauma, and infection. More recently, it has become clear that lncRNAs contribute to regulating both pro-inflammatory and anti-inflammatory pathways in the CNS. In this review, we discuss the molecular pathways involved in the expression of lncRNAs, their role and mechanism of action during gene regulation,...
Source: Molecular Neurobiology - February 8, 2021 Category: Neurology Source Type: research
Obscure Involvement of MYC in Neurodegenerative Diseases and Neuronal Repair
AbstractMYC is well known as a potent oncogene involved in regulating cell cycle and metabolism. Augmented MYC expression leads to cell cycle dysregulation, intense cell proliferation, and carcinogenesis. Surprisingly, its increased expression in neurons does not induce their proliferation, but leads to neuronal cell death and consequent development of a neurodegenerative phenotype. Interestingly, while cancer and neurodegenerative diseases such as Alzheimer ’s disease are placed at the opposite sides of cell division spectrum, both start with cell cycle dysregulation and stimulation of proliferation. It seems that MYC a...
Source: Molecular Neurobiology - May 5, 2021 Category: Neurology Source Type: research
