CDK4 and CDK5 Inhibition Have Comparable Mild Hypothermia Effects in Preventing Drp1-Dependent Mitochondrial Fission and Neuron Death Induced by MPP +
AbstractMild hypothermia has promising effects in the treatment of acute brain insults and also affects cell cycle progression. Mitochondrial dynamics, fusion and fission, are changed along with the cell cycle and disrupted in neurodegenerative diseases, including Parkinson ’s disease (PD). However, the effects of hypothermia on aberrant mitochondrial dynamics in PD remain unknown. We hypothesized that mild hypothermia protects neurons by regulating cell cycle-dependent protein expression and mitochondrial dynamics in a 1-methyl-4-phenylpyridinium (MPP+)-induced cell model of PD. We found that the hypothermia treatme...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

The Microbiota-Gut-Immune-Glia (MGIG) Axis in Major Depression
AbstractThere is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons, orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms, and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Erythropoietin-Induced Autophagy Protects Against Spinal Cord Injury and Improves Neurological Function via the Extracellular-Regulated Protein Kinase Signaling Pathway
The objective of this study was to explore the neuroprotective molecular mechanisms of erythropoietin (EPO) in rats following spinal cord injury (SCI). First, a standard SCI model was established. After drug or saline treatment was administered, locomotor function was evaluated in rats using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. H&E, Nissl, and TUNEL staining were performed to assess the ratio of cavities, number of motor neurons, and apoptotic cells in the damaged area. The relative protein and mRNA expressions were examined using western blot and qRT-PCR analyses, and the inflammatory marker...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ischemic Stroke: Involvements of EGFR/PI3K/Akt/Bad/14-3-3 and Jak2/Stat3/Cyclin D1 Signaling Cascades
AbstractBuyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for 200  years. In the present study, we investigated the effects of BHD on inhibiting neuronal apoptosis, promoting proliferation and differentiation of neural stem cells (NSCs) and neurite formation and enhancing learning and memory functional recovery in an experimental rat ischemic stroke model. BHD si gnificantly reduced infarct volume and decreased cell apoptosis in the ischemic brain. BHD enhanced neuronal cell viability ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Variability in Cerebrospinal Fluid MicroRNAs Through Life
In this study, we aimed to highlight the biological variability of miRNA expression in the CSF throughout life, which is also crucial for biomarker discovery in CNS pathologies, especially in children, where they are desperately needed. We analyzed the CSF microRNAome of 14 healthy children (aged 0 –7.4 years) by smallRNA-Seq and compared it with previously published data in adults (N = 7) and elders (N = 11). miR-423-5p and miR-22-3p were overexpressed in the  3 years groups, respectively. Additionally, we detected 18 miRNAs that reached their highest peak of expression a...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Tau Protein as a New Regulator of Cellular Prion Protein Transcription
AbstractCellular prion protein (PrPC) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrPSC. Physiological functions of PrPC include protective roles against oxidative stress and excitotoxicity. Relevantly, PrPC downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer ’s disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrPC. However, the ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Optogenetic Activation of Dopamine Receptor D1 and D2 Neurons in Anterior Cingulate Cortex Differentially Modulates Trigeminal Neuropathic Pain
In this study, we investigated the effect of optogenetic activation of ACC dopamine receptors D1- and D2-expressing neurons on trigeminal neuropathic pain. Chronic constriction injury of infraorbital nerve (CCI-ION) was carried out to induce trigeminal neuropathic pain in mice. We conducted optogenetic stimulation to specifically activate D1- and D2-expressing neurons in the ACC. Western blotting and immunofluorescence staining were used to examine ACC D1 and D2 expression and localization. The von Frey and real-time place preference tests were performed to measure evoked mechanical pain and nonreflexive emotional pain beh...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Temporally Altered miRNA Expression in a Piglet Model of Hypoxic Ischemic Brain Injury
AbstractHypoxic ischemic encephalopathy (HIE) is the most frequent cause of acquired infant brain injury. Early, clinically relevant biomarkers are required to allow timely application of therapeutic interventions. We previously reported early alterations in several microRNAs (miRNA) in umbilical cord blood at birth in infants with HIE. However, the exact timing of these alterations is unknown. Here, we report serial changes in six circulating, cross-species/bridging biomarkers in a clinically relevant porcine model of neonatal HIE with functional analysis. Six miRNAs —miR-374a, miR-181b, miR-181a, miR-151a, miR-148a...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Role of Circular Ribonucleic Acids in the Treatment of Traumatic Brain and Spinal Cord Injury
AbstractThe causal and pathogenetic factors linked to traumatic brain injury (TBI) and spinal cord injury (SCI) are complex. This complexity is a contributive factor in the minimal improvement outcomes of injured individuals. Several studies have demonstrated the potentiality of stem cells in facilitating neuronal growth and improve outcome in various neurological conditions, including TBI and SCI. However, the efficiency concerning stem cell delivery at injured sites is open to question. Circular ribonucleic acids (circular RNAs) have recently been the focus of attention owing to their disparate functions and features in ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Extracellular Vesicles of Alzheimer ’s Disease Patients as a Biomarker for Disease Progression
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patien ts’ EVs on disease progression. Blood samples were collected after obtaining signed informed consent (No. 0462-14-RMB) from 42 AD patients at three stages of disease severity and from 19 healthy controls (HC). EV size and concentration were studied by nanotracking analysis. EV membrane antigens we re...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Ouabain Modulates the Functional Interaction Between Na,K-ATPase and NMDA Receptor
AbstractThe N-methyl-D-aspartate (NMDA) receptor plays an essential role in glutamatergic transmission and synaptic plasticity and researchers are seeking for different modulators of NMDA receptor function. One possible mechanism for its regulation could be through adjacent membrane proteins. NMDA receptors coprecipitate with Na,K-ATPase, indicating a potential interaction of these two proteins. Ouabain, a mammalian cardiotonic steroid that specifically binds to Na,K-ATPase and affects its conformation, can protect from some toxic effects of NMDA receptor activation. Here we have examined whether NMDA receptor activity and...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Mechanistic Insights of Astrocyte-Mediated Hyperactive Autophagy and Loss of Motor Neuron Function in SOD1 L39R Linked Amyotrophic Lateral Sclerosis
We report that the higher expression of stress granule (SG) marker protein G3BP1, and its co-localization with the mutated Cu/Zn-SOD1L39R protein in patient ’s MNs and astrocytes are linked with AIF1-mediated upregulation of caspase 3/7 and hyper activated autophagy. We also observe the astrocyte-mediated non-cell autonomous neurotoxicity on MNs in ALS. The secretome of the patient’s iPSC-derived astrocytes exerts significant oxidative stress in MNs . The findings suggest the hyperactive status of autophagy in MNs, as witnessed by the co-distribution of LAMP1, P62 and LC3 I/II with the autolysosomes. Conversely...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Relevance of Mitochondrial Dysfunction in the Reserpine-Induced Experimental Fibromyalgia Model
AbstractFibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitoch...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Oligodendrocyte Response to Pathophysiological Conditions Triggered by Episode of Perinatal Hypoxia-Ischemia: Role of IGF-1 Secretion by Glial Cells
AbstractDifferentiation of oligodendrocyte progenitors towards myelinating cells is influenced by a plethora of exogenous instructive signals. Insulin-like growth factor 1 (IGF-1) is one of the major factors regulating cell survival, proliferation, and maturation. Recently, there is an ever growing recognition concerning the role of autocrine/paracrine IGF-1 signaling in brain development and metabolism. Since oligodendrocyte functioning is altered after the neonatal hypoxic-ischemic (HI) insult, a question arises if the injury exerts any influence on the IGF-1 secreted by neural cells and how possibly the change in IGF-1 ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in Rats
AbstractWe investigate the anti-inflammatory effects of injectable hydrogel containing tauroursodeoxycholic acid (TUDCA) in a spinal cord injury (SCI) model. To this end, TUDCA-hydrogel (TC gel) is created by immersing the synthesized hydrogel in a TUDCA solution for 1  h. A mechanical SCI was imposed on rats, after which we injected the TC gel. After the SCI and injections, motor functions and lesions were significantly improved in the TC gel group compared with those in the saline group. The TC gel significantly decreased pro-inflammatory cytokine levels compar ed with the saline; TUDCA and glycol chitosan-oxidized ...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence
This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition and transcription. Young Fischer 344 X Brown Norway hybrid rats were given intraperitoneal injections once a week for 7  weeks with either LPS or vehicle. Older rats received a similar injection schedule of vehicle. Old vehicle and young LPS rats exhibited a delay-dependent impairment in spatial memory. Further, LPS treatment reduced the hippocampal CA3–CA1 synaptic response. RNA sequencing, performed on CA1, indi cated an increase in genes linked to neuroinflamma...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics
AbstractThe coronavirus disease of 2019 (COVID-19) is a pandemic disease that has taken the lives of many around the world. It is caused by severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). To date, the USA, Italy, Spain, France, Russia, and the UK have been hit the hardest by the virus. However, death counts are still rising. Some nations have managed to “flatten” the death rate via protective measures such physical distancing, quarantine measures, and therapeutic management. The structure of the SARS-CoV-2 virus comprises of S proteins, M proteins, E proteins, hemagglutinin esterases, nucleocapsi...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Platelet-Activating Factor Deteriorates Lysophosphatidylcholine-Induced Demyelination Via Its Receptor-Dependent and -Independent Effects
AbstractAccumulating evidence suggests that platelet-activating factor (PAF) increases the inflammatory response in demyelinating diseases such as multiple sclerosis. However, PAF receptor (PAFR) antagonists do not show therapeutic efficacy for MS, and its underlying mechanisms remain poorly understood. In the present study, we investigated the effects of PAF on an ex vivo demyelination cerebellar model following lysophosphatidylcholine (LPC, 0.5  mg/mL) application using wild-type andPAFR conventional knockout (PAFR-KO) mice. Demyelination was induced in cerebellar slices that were cultured with LPC for 18  h. E...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile
AbstractPeripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration. Nevertheless, the molecular alterations at the transcriptomic level associated with these compensatory growth mecha...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Seasonal Variations in Macrophages/Microglia Underlie Changes in the Mouse Model of Multiple Sclerosis Severity
AbstractBoth immune and neurodegenerative mechanisms underlie multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). MS/EAE are triggered by encephalitogenic immune cells, including Th1 and Th17 cells, whereas T regulatory (Treg) cells are involved in inflammation resolution. Pro-inflammatory macrophages/microglia also play a deleterious role in the disease. Seasonal variations in MS relapses, active lesions, and pro- and anti-inflammatory cytokine levels have been described in MS patients and have been related with both perinatal and adult exposure to sunlight and other environmenta...
Source: Molecular Neurobiology - September 2, 2020 Category: Neurology Source Type: research

Large-Scale Analysis Reveals Gene Signature for Survival Prediction in Primary Glioblastoma
In conclusion, our integrated analysis using meta-analysis approach maximizes the use of the available gene expression data and robustly identified a 4-gene panel for predicting survival in primary GBM. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - September 1, 2020 Category: Neurology Source Type: research

Increased Seizure Susceptibility for Rats Subject to Early Life Hypoxia Might Be Associated with Brain Dysfunction of NRG1-ErbB4 Signaling in Parvalbumin Interneurons
AbstractNeuregulin 1 (NRG1) –induced activation of ErbB4 in parvalbumin (PV) inhibitory interneurons is reported to serve as a critical endogenous negative-feedback mechanism to repress brain epileptogenesis. Here, we investigated the seizure susceptibility and the role of NRG1-ErbB4 signaling in PV interneurons in the suppr ession of epileptic seizures for rats subject to early life hypoxia. Neonatal postnatal day 5 (P5) rats were exposed to intermittent hypoxia (IH) or control (CON) room air for 10 days. In the prefrontal cortex (PFC) of P54 rats, we determined the impact of neonatal IH exposures on the expression ...
Source: Molecular Neurobiology - September 1, 2020 Category: Neurology Source Type: research

Advances in the Understanding of Oxaliplatin-Induced Peripheral Neuropathy in Mice: 7-Chloro-4-(Phenylselanyl) Quinoline as a Promising Therapeutic Agent
In this study, the deposition of platinum in oxaliplatin (OXA)-exposed mice and the effects of the oxidative damage on the central nervous system were investigated. The relationship between the reactive species (RS) levels as well as the expression and activity of enzymes, such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and acetylcholinesterase (AChE), in the development of peripheral neuropathy after OXA exposure, was evidenced. The effects of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on OXA-induced peripheral neuropathy was also investigated.Swiss mice received OXA (10  mg kg...
Source: Molecular Neurobiology - September 1, 2020 Category: Neurology Source Type: research

Chronic Administration of Scopolamine Increased GSK3 βP9, Beta Secretase, Amyloid Beta, and Oxidative Stress in the Hippocampus of Wistar Rats
AbstractThe increase of amyloid beta (A β) release and hyperphosphorylation of Tau protein represents the main events related to Alzheimer’s disease (AD). Furthermore, the sporadic type represents the most common form of AD. Therefore, the establishment of a non-transgenic animal model that resembles the characteristics of the disease is of particular importance. Scopolamine has been linked to increases in both Aβ production and oxidative stress in rat and mice brains. Thus, the purpose of the present work was to identify changes in biomarkers that are related to AD after chronic administration of scopolami...
Source: Molecular Neurobiology - August 4, 2020 Category: Neurology Source Type: research

Guanosine Promotes Proliferation in Neural Stem Cells from Hippocampus and Neurogenesis in Adult Mice
AbstractNeural stem cells can generate new neurons in the mouse adult brain in a complex multistep process called neurogenesis. Several factors regulate this process, including neurotransmitters, hormones, neurotrophic factors, pharmacological agents, and environmental factors. Purinergic signaling, mainly the adenosinergic system, takes part in neurogenesis, being involved in cell proliferation, migration, and differentiation. However, the role of the purine nucleoside guanosine in neurogenesis remains unclear. Here, we examined the effect of guanosine by using the neurosphere assay derived from neural stem cells of adult...
Source: Molecular Neurobiology - August 4, 2020 Category: Neurology Source Type: research

Induction of BIS Protein During Astroglial and Fibrotic Scar Formation After Mitochondrial Toxin-Mediated Neuronal Injury in Rats
AbstractB cell leukemia/lymphoma-2 (Bcl-2)-interacting death suppressor (BIS), also identified as Bcl-2-associated athanogene 3 (BAG3), has been reported to be upregulated in reactive astrocytes after brain insults. The present study was designed to further substantiate the involvement of BIS protein in the astroglial reaction in the striatum of rats treated with the mitochondrial toxin, 3-nitropropionic acid. Weak constitutive immunoreactivity for BIS was observed in astrocytes in the control striatum, whereas its expression was upregulated, along with that of nestin, in the lesioned striatum. In the lesion core, where as...
Source: Molecular Neurobiology - August 4, 2020 Category: Neurology Source Type: research

Nuclear Respiratory Factor 1 (NRF1) Transcriptional Activity-Driven Gene Signature Association with Severity of Astrocytoma and Poor Prognosis of Glioblastoma
AbstractDespite tremendous progress in understanding the pathobiology of astrocytoma, major gaps remain in our knowledge of the molecular basis underlying the aggressiveness of high-grade astrocytoma (glioblastoma - GBM). Recently, we and others have shown nuclear respiratory factor 1 (NRF1) transcription factor being highly active in human cancers, but its role in astrocytoma remains unknown. Therefore, the purpose of this study was to uncover the role of NRF1 in the progression of GBM. NRF1 has higher mRNA expression and transcription factor activity in astrocytoma compared to non-tumor brain tissue. NRF1 activity also c...
Source: Molecular Neurobiology - August 4, 2020 Category: Neurology Source Type: research

Correction to: Preconditioning with VEGF Enhances Angiogenic and Neuroprotective Effects of Bone Marrow Mononuclear Cell Transplantation in a Rat Model of Chronic Cerebral Hypoperfusion
The original version of this article unfortunately contained a careless error in Fig. 2b –c, where the pictures of group Vehicle were the same with group VEGF. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - August 4, 2020 Category: Neurology Source Type: research

Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons
AbstractTranscriptional and epigenetic regulation of both dopaminergic neurons and their accompanying glial cells is of great interest in the search for therapies for neurodegenerative disorders such as Parkinson ’s disease (PD). In this review, we collate transcriptional and epigenetic changes identified in adultDrosophila melanogaster dopaminergic neurons in response to either prolonged social deprivation or social enrichment, and compare them with changes identified in mammalian dopaminergic neurons during normal development, stress, injury, and neurodegeneration. Surprisingly, a small set of activity-regulated ge...
Source: Molecular Neurobiology - August 3, 2020 Category: Neurology Source Type: research

Sharing of Genetic Association Signals by Age-Related Macular Degeneration and Alzheimer ’s Disease at Multiple Levels
This study was conducted to investigate the genetic factors shared by both diseases. We analyzed genome-wide association studies’ summary statistics from both diseases using a new platform k nown as functional mapping and annotation (FUMA) and a co-localization analysis. We obtained disease-related gene expression profile data from the Gene Expression Omnibus and analyzed these data using weighted gene co-expression network analysis. FUMA analysis and Bayesian co-localization analysis s howed that ten genes on chromosome 7, one pathway (complement and coagulation cascade), and forty-two biological processes were comm...
Source: Molecular Neurobiology - August 3, 2020 Category: Neurology Source Type: research

A Novel Interaction of Translocator Protein 18  kDa (TSPO) with NADPH Oxidase in Microglia
In this study, we explored a putative interaction between TSPO and NADPH oxidase 2 (NOX2) in microglia. We found that TSPO associates with gp91phox and p22phox, the principal subunits of NOX2 in primary murine microglia. The association of TSPO with gp91phox and p22phox was observed using co-immunoprecipitation, confocal immunofluorescence imaging, and proximity ligation assay. We found that besides gp91phox and p22phox, voltage-dependent anion channel (VDAC) also co-immunoprecipitated with TSPO consistent with previous reports. When we compared lipopolysaccharide (LPS) stimulated microglia to vehicle control, we found tha...
Source: Molecular Neurobiology - August 2, 2020 Category: Neurology Source Type: research

Lipoic Acid and Fish Oil Combination Potentiates Neuroinflammation and Oxidative Stress Regulation and Prevents Cognitive Decline of Rats After Sepsis
AbstractSepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopo...
Source: Molecular Neurobiology - August 2, 2020 Category: Neurology Source Type: research

Exposure to Novelty Promotes Long-Term Contextual Fear Memory Formation in Juvenile Mice: Evidence for a Behavioral Tagging
In this study, we asked whether exposure to a novel environment, a process named “behavioral tagging,” may promote the persistence of weak memories in male juvenile mice. Using a contextual fear conditioning (CFC) paradigm, we found that a weak training protocol, which typically induces a transient form of memory, results in LTM when paired with an exploration to a novel but not a familiar environment that occurs close in time to the training session. The promoting effect of the novel context exploration (NCE) on CFC-LTM formation is dependent on the activation of dopamine D1/D5 receptors and requires novel pro...
Source: Molecular Neurobiology - July 6, 2020 Category: Neurology Source Type: research

Upregulation of miR-133a-3p in the Sciatic Nerve Contributes to Neuropathic Pain Development
AbstractThe micro (mi)RNAs expressed in the sciatic nerve of streptozotocin (STZ)-induced diabetic rats were evaluated in terms of their therapeutic potential in patients with diabetic neuropathic pain (DNP). Relative miRNA expression in sciatic nerve with DNP was analyzed using next-generation sequencing and quantitative PCR. Potential downstream targets of miRNAs were predicted using Ingenuity Pathway Analysis and the TargetScan database. In vitro experiments were performed using miR-133a-3p-transfected RSC96 Schwann cells. We performed micro-Western and Western blotting and immunofluorescence analyses to verify the role...
Source: Molecular Neurobiology - July 6, 2020 Category: Neurology Source Type: research

Conventional Treatment of Glioblastoma Reveals Persistent CD44 + Subpopulations
In this study, we intracranially implanted primary GBM cells into mice which underwent conventional GBM treatments, including irradiation, temozolomide, and a combination. We obtained single cell suspensions through a combination of mechanical and enzymatic dissociation of brain tissue and investigated in detail the changes in GBM cells in response to conventional treatments in vivo using multi-color flow cytometry and cl uster analysis. CD44 expression was elevated in all treatment groups, which was confirmed by subsequent immunohistochemistry. High CD44 expression was furthermore shown to correlate with poor prognosis of...
Source: Molecular Neurobiology - July 6, 2020 Category: Neurology Source Type: research

The Study of Genetic Susceptibility and Mitochondrial Dysfunction in Mesial Temporal Lobe Epilepsy
AbstractThe aim of this study is to investigate the mitochondrial dysfunction and pathogenic role of the mitochondrial genome in the progression of mesial temporal lobe epilepsy (MTLE) in vivo and in vitro. Mitochondrial DNA (mtDNA) and nuclear DNA were detected in the hippocampal samples and peripheral blood of patients with MTLE. Mitochondrial functions were detected in vivo and in vitro. In 20 patients with MTLE, mtDNA mutations involving single or multiple deletions in the hippocampus were found in 5 patients but were not detected in the peripheral blood. Two patients carried pathogenic mutations ofRELN, both in the hi...
Source: Molecular Neurobiology - July 6, 2020 Category: Neurology Source Type: research

Caffeine Consumption plus Physical Exercise Improves Behavioral Impairments and Stimulates Neuroplasticity in Spontaneously Hypertensive Rats (SHR): an Animal Model of Attention Deficit Hyperactivity Disorder
AbstractAttention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including alterations in adenosine neuromodulation. The administration of caffeine (a non-selective adenosine receptor antagonist) and physical exercise have been independently pointed as effective approaches for the management of ADHD symptoms. Here, we evaluated the effects of caff...
Source: Molecular Neurobiology - July 3, 2020 Category: Neurology Source Type: research

Correction to: Embelin Attenuates Intracerebroventricular Streptozotocin-Induced Behavioral, Biochemical, and Neurochemical Abnormalities in Rats
The original version of this article unfortunately missed to include the other affiliation of the first authorRimpi Arora as listed below. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 3, 2020 Category: Neurology Source Type: research

Mitochondrial Transplantation Attenuates Brain Dysfunction in Sepsis by Driving Microglial M2 Polarization
In this study, lipopolysaccharide (LPS)/interferon- γ (IFN-γ) and interleukin-4 (IL-4)/interleukin-13 (IL-13) were used to induce different phenotypes of BV2 microglial cells. We observed that mitochondrial content and function were enhanced in IL-4-/IL-13-stimulated microglia. In vitro, mitochondria treatment conferred neuroprotection by enhancing microglial polarization from the M1 phenotype to the M2 phenotype and suppressing microglial-derived inflammatory cytokine release. Furthermore, microglial phenotypes and behavior tests were assessed after mice were subjected to sepsis by cecal ligation and puncture ...
Source: Molecular Neurobiology - July 1, 2020 Category: Neurology Source Type: research

Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice
AbstractBlood-brain barrier disruption is one of the hallmarks of multiple sclerosis. Mesenchymal stem cells showed great potential for the multiple sclerosis therapy. However, the effect of mesenchymal stem cells on blood-brain barrier in multiple sclerosis remains unclear. Here, we investigated whether mesenchymal stem cells transplantation protected blood-brain barrier integrity and further explored possible underlying mechanisms. Adult female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptide33-55 (MOG33-55) to induce experimental autoimmune encephalomyelitis (EAE). Mesenchymal stem cells (5 &...
Source: Molecular Neurobiology - July 1, 2020 Category: Neurology Source Type: research

Mitochondrial Dysfunction: a Potential Therapeutic Target to Treat Alzheimer ’s Disease
AbstractMitochondrial dysfunction plays a very vital role in the pathogenesis of Alzheimer ’s disease (AD). Several shreds of evidence have indicated that the mitochondrial function is severely compromised under AD pathogenesis. Most of the recent therapeutic strategies have been conversed to treat AD by pinpointing the pathways involved in the pathophysiology of AD. In AD, mitochondria progressively lose their proper functions that are ultimately responsible for their accumulation and removal via the autophagic process, which is called mitophagy that further worsens the progression of this incapacitating disease. Pr...
Source: Molecular Neurobiology - June 26, 2020 Category: Neurology Source Type: research

Hippocampal Metabolite Profiles in Two Rat Models of Autism: NMR-Based Metabolomics Studies
AbstractAutism spectrum disorders (ASDs) are increasingly being diagnosed. Hypotheses link ASD to genetic, epigenetic, or environmental factors. The role of oxidative stress and the imbalance between excitatory and inhibitory neurotransmission in the pathogenesis of ASD has been suggested. Rats in which ASD symptoms are induced by valproate (VPA) or thalidomide (THAL) application in utero are useful models in ASD studies. Our study investigated whether rats in ASD models show changes in metabolite levels in the brain consistent with the hypothetical pathomechanisms of ASD. Female rats were fed one dose of 800  mg/kg V...
Source: Molecular Neurobiology - June 26, 2020 Category: Neurology Source Type: research

Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs
In this study, we explored the potential of the neuronal cytoskeletal protein neurofilament light chain (NfL) as a biomarker of neuro-aging in dogs using an ultrasensitive single-molecule array assay to measure plasma concentrations. Healthy dogs of different ages and dogs affected with CCD and DM were evaluated. The mean plasma NfL concentrations in the different age groups of the healthy population were as follows: 4.55 ± 1.70 pg/mL in puppy/junior group (0.43–2 years), 13.51 ± 6.8 pg/mL in adult/mature group (2.1–9 years), and 47.1  ±...
Source: Molecular Neurobiology - June 26, 2020 Category: Neurology Source Type: research

SORLA Expression in Synaptic Plexiform Layers of Mouse Retina
AbstractSorting protein –related receptor containing LDLR class A repeats (SORLA; also known as LR11) exerts intraneuronal trafficking functions in the central nervous system. Recently, involvement of SORLA in retinogenesis was proposed, but no studies have examined yet in detail the expression pattern of this sorting re ceptor in the retina. Here, we provide a spatio-temporal characterization ofSORL1 mRNA and its translational product SORLA in the postnatal mouse retina. Using stereological analysis, we confirmed previous studies showing that receptor depletion in knockout mice significantly reduces the number of ce...
Source: Molecular Neurobiology - June 26, 2020 Category: Neurology Source Type: research

Molecular Mechanisms for Kr üppel-Like Factor 13 Actions in Hippocampal Neurons
AbstractKr üppel-like factors (KLFs) play key roles in nervous system development and function. Several KLFs are known to promote, and then maintain neural cell differentiation. Our previous work focused on the actions of KLF9 in mouse hippocampal neurons. Here we investigated genomic targets and functions of KLF9’s paralog KLF13, with the goal of understanding how these two closely related transcription factors influence hippocampal cell function, proliferation, survival, and regeneration. We engineered the adult mouse hippocampus-derived cell line HT22 to controlKlf13 expression with doxycycline. We also gener...
Source: Molecular Neurobiology - June 23, 2020 Category: Neurology Source Type: research

The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of A β42 and Its Protein Aggregates
This study suggests that the complex may potentially be a novel pharmacological target to decrease neuronal Aβ42 internalization and accumulation, which may represent a new strategy for inhibiting the rate of neurotoxicity, neurodegeneration, and progression of AD. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - June 23, 2020 Category: Neurology Source Type: research

Caveolin-1 Ablation Imparts Partial Protection Against Inner Retinal Injury in Experimental Glaucoma and Reduces Apoptotic Activation
This study corroborated previous findings of enhanced Shp2 phosphorylation in a chronic glaucoma model and established a novel role of Cav-1 in mediating activation of this phosphatase in the inner retina in vivo. Collectively, these findings highlight the critical involvement of Cav-1 regulatory mechanisms in ganglion cells in response to increased IOP, implicating Cav-1 as a potential therapeutic target in glaucoma. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - June 23, 2020 Category: Neurology Source Type: research

Silencing of LRP1 Exacerbates Inflammatory Response Via TLR4/NF- κB/MAPKs Signaling Pathways in APP/PS1 Transgenic Mice
AbstractActivation of glial cells (including microglia and astrocytes) appears central to the initiation and progression of neuroinflammation in Alzheimer ’s disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for amyloid-β (Aβ), which plays a critical role in AD pathogenesis. LRP1 regulates inflammatory response by modulating the release of pro-inflammatory cytokines and phagocytosis. However, the effec ts of LRP1 on microglia- and astrocytic cell-mediated neuroinflammation and their underlying mechanisms in AD remain unclear. Therefore, using APP/PS1 transgenic ...
Source: Molecular Neurobiology - June 22, 2020 Category: Neurology Source Type: research

Roles of Prokineticin 2 in Subarachnoid Hemorrhage-Induced Early Brain Injury via Regulation of Phenotype Polarization in Astrocytes
This study aimed to examine the role of PK2 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH). SAH-induced astrocytic activation was confirmed by Western blotting. We confirmed C3 an d PTX3 as appropriate reactivity markers for discriminating A1 and A2 astrocytes, respectively. We also observed SAH-induced astrocytic activation in SAH patients. The increase of PK2 in neurons after SAH in both humans and rats suggested a possible relationship between PK2 and SAH pathology. PK2 kn ockdown promoted an A1 astrocytic phenotype with upregulation of neurodegenerative indicators, while intravascular injection of ...
Source: Molecular Neurobiology - June 22, 2020 Category: Neurology Source Type: research

Correction to: Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus
The original version of this article unfortunately contained some mistake. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - June 22, 2020 Category: Neurology Source Type: research