Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses
AbstractPerinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses ’ brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain develo...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Neuroinflammation, Gut Microbiome, and Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients’ life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. This review int rod...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Rhythmic Diurnal  Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation
AbstractVitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction ofAa...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration
AbstractMating behavior in males and females is dependent on olfactory cues processed through both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Signaling through the MOE is critical for the initiation of male mating behavior, and the loss of MOE signaling severely compromises this comportment. Here, we demonstrate that dosage of the homeodomain geneSix3 affects the degree of development of MOE but not the VNO. Anomalous MOE development inSix3 heterozygote mice leads to hyposmia, specifically disrupting male mounting behavior by impairing detection of volatile female estrus pheromones.Six3 is highly ...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

TRPV4: a Sensor for Homeostasis and Pathological Events in the CNS
AbstractTransient receptor potential vanilloid type 4 (TRPV4) was originally described as a calcium-permeable nonselective cation channel. TRPV4 is now recognized as a polymodal ionotropic receptor: it is a broadly expressed, nonselective cation channel (permeable to calcium, potassium, magnesium, and sodium) that plays an important role in a multitude of physiological processes. TRPV4 is involved in maintaining homeostasis, serves as an osmosensor and thermosensor, can be activated directly by endogenous or exogenous chemical stimuli, and can be activated or sensitized indirectly via intracellular signaling pathways. Addi...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Recovery of Neurovascular Unit Integrity by CDK5-KD Astrocyte Transplantation in a Global Cerebral Ischemia Model
AbstractAstrocytes play metabolic and structural support roles and contribute to the integrity of the blood-brain barrier (BBB), linking communication between neurons and the endothelium. Cyclin-dependent kinase 5 (CDK5) likely exerts a dual effect on the endothelium and astrocytes due to its involvement in migration and angiogenesis; the overactivation of CDK5 is associated with dysfunction in glutamate recapture and hypoxia. Recently, we proposed that CDK5-targeted astrocytes facilitate the recovery of neurological and motor function in transplanted ischemic rats. In the current study, we treated cerebral ischemic rats a...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury
In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7  days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle- injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exer...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices
This study elucidates some of the protective effects of KYNA against the damage caused by QUIN toxicity. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Diabetes Mellitus as a Risk Factor for Parkinson ’s Disease: a Molecular Point of View
AbstractType 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated concentrations of glucose in the blood. The chronic hyperglycemic state accounts for most of the vascular complications associated to the disease and the prevalent mechanism proposed is related to the glycating chemistry mediated by methylglyoxal (MG), which accumulates in T2DM. In recent years, a higher risk of Parkinson ’s disease (PD) onset in people affected by T2DM has become evident, but the molecular mechanisms underlying the interplay between T2DM and PD are still unknown. The oxidative chemistry of dopamine and its reac...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Transcriptional and Epigenetic Control of Mammalian Olfactory Epithelium Development
AbstractThe postnatal mammalian olfactory epithelium (OE) represents a major aspect of the peripheral olfactory system. It is a pseudostratified tissue that originates from the olfactory placode and is composed of diverse cells, some of which are specialized receptor neurons capable of transducing odorant stimuli to afford the perception of smell (olfaction). The OE is known to offer a tractable miniature model for studying the systematic generation of neurons and glia that typify neural tissue development. During OE development, stem/progenitor cells that will become olfactory sensory neurons and/or non-neuronal cell type...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

N -palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice
AbstractParkinson ’s disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD ind uced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model. Male CD mice (21 months of age) were pre-treated for 60 days with PEAm. After this...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Differential Behavioral and Biochemical Responses to Caffeine in Male and Female Rats from a Validated Model of Attention Deficit and Hyperactivity Disorder
AbstractEpidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3  g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats—SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in ad...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons
In this study, we assessed the potential therapeutic properties of the whole body periodic acceleration (pGz) to ameliorate the pathology observed in cortical neurons from themdx mouse. pGz adds small pulses to the circulation, thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of nitric oxide (NO). We found [Ca2+]i and [Na+]i overload along with reactive oxygen species (ROS) overproduction inmdx neurons and cognitive dysfunction.mdx neurons showed increased activity of superoxide dismutase, glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell...
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...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

A Novel Five-Node Feed-Forward Loop Unravels miRNA-Gene-TF Regulatory Relationships in Ischemic Stroke
AbstractThe complex and interlinked cascade of events regulated by microRNAs (miRNAs), transcription factors (TF), and target genes highlight the multifactorial nature of ischemic stroke pathology. The complexity of ischemic stroke requires a wider assessment than the existing experimental research that deals with only a few regulatory components. Here, we assessed a massive set of genes, miRNAs, and transcription factors to build a miRNA-gene-transcription factor regulatory network to elucidate the underlying post-transcriptional mechanisms in ischemic stroke. Feed-forward loops (three-node, four-node, and novel five-node...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

P2Y 12 but not P2Y 13 Purinergic Receptor Controls Postnatal Rat Retinogenesis In Vivo
AbstractAdenine nucleotides through P2Y1 receptor stimulation are known to control retinal progenitor cell (RPC) proliferation by modulating expression of the p57KIP2, a cell cycle regulator. However, the role of Gi protein-coupled P2Y12 and P2Y13 receptors also activated by adenine nucleotides in RPC proliferation is still unknown. Gene expression of the purinergic P2Y12 subtype was detected in rat retina during early postnatal days (P0 to P5), while expression levels of P2Y13 were low. Immunohistochemistry assays performed with rat retina on P3 revealed P2Y12 receptor expression in both Ki-67-positive cells in the neurob...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie
AbstractThe analysis of the cerebrospinal fluid (CSF) biomarkers in patients with suspected prion diseases became a useful tool in diagnostic routine. Prion diseases can only be identified at clinical stages when the disease already spread throughout the brain and massive neuronal damage occurs. Consequently, the accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical and clinical naturally occurring scrapie. While decreased total prion protein (PrP) levels and positive PrP seeding activity were already detectable at pre...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

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

Deficiency of Tenascin-C Alleviates Neuronal Apoptosis and Neuroinflammation After Experimental Subarachnoid Hemorrhage in Mice
This study first provided the direct evidence that TNC causes post-SAH neuronal apoptosis and neuroinflammation, potentially leading to the development of a new molecular targeted therapy against EBI. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Role of Chimeric Antigen Receptor T Cell Therapy in Glioblastoma Multiforme
AbstractGlioblastoma multiforme (GBM) is the most common primary malignant cancer of brain, which is extremely aggressive and carries a dreadful prognosis. Current treatment protocol runs around radiotherapy, surgical resection, and temozolomide with median overall survival of around 12 –15 months. Due to its heterogeneity and mutational load, immunotherapy with chimeric antigen receptor (CAR) T cell therapy can be a promising treatment option for recurrent glioblastoma. Initial phase 1 studies have shown that this therapy is safe without dose-limiting side effects and it also h as a better clinical outcome. The...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses
AbstractPerinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses ’ brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain develo...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Neuroinflammation, Gut Microbiome, and Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients’ life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. This review int rod...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Rhythmic Diurnal  Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation
AbstractVitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction ofAa...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration
AbstractMating behavior in males and females is dependent on olfactory cues processed through both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Signaling through the MOE is critical for the initiation of male mating behavior, and the loss of MOE signaling severely compromises this comportment. Here, we demonstrate that dosage of the homeodomain geneSix3 affects the degree of development of MOE but not the VNO. Anomalous MOE development inSix3 heterozygote mice leads to hyposmia, specifically disrupting male mounting behavior by impairing detection of volatile female estrus pheromones.Six3 is highly ...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

TRPV4: a Sensor for Homeostasis and Pathological Events in the CNS
AbstractTransient receptor potential vanilloid type 4 (TRPV4) was originally described as a calcium-permeable nonselective cation channel. TRPV4 is now recognized as a polymodal ionotropic receptor: it is a broadly expressed, nonselective cation channel (permeable to calcium, potassium, magnesium, and sodium) that plays an important role in a multitude of physiological processes. TRPV4 is involved in maintaining homeostasis, serves as an osmosensor and thermosensor, can be activated directly by endogenous or exogenous chemical stimuli, and can be activated or sensitized indirectly via intracellular signaling pathways. Addi...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Recovery of Neurovascular Unit Integrity by CDK5-KD Astrocyte Transplantation in a Global Cerebral Ischemia Model
AbstractAstrocytes play metabolic and structural support roles and contribute to the integrity of the blood-brain barrier (BBB), linking communication between neurons and the endothelium. Cyclin-dependent kinase 5 (CDK5) likely exerts a dual effect on the endothelium and astrocytes due to its involvement in migration and angiogenesis; the overactivation of CDK5 is associated with dysfunction in glutamate recapture and hypoxia. Recently, we proposed that CDK5-targeted astrocytes facilitate the recovery of neurological and motor function in transplanted ischemic rats. In the current study, we treated cerebral ischemic rats a...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury
In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7  days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle- injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exer...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices
This study elucidates some of the protective effects of KYNA against the damage caused by QUIN toxicity. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Diabetes Mellitus as a Risk Factor for Parkinson ’s Disease: a Molecular Point of View
AbstractType 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated concentrations of glucose in the blood. The chronic hyperglycemic state accounts for most of the vascular complications associated to the disease and the prevalent mechanism proposed is related to the glycating chemistry mediated by methylglyoxal (MG), which accumulates in T2DM. In recent years, a higher risk of Parkinson ’s disease (PD) onset in people affected by T2DM has become evident, but the molecular mechanisms underlying the interplay between T2DM and PD are still unknown. The oxidative chemistry of dopamine and its reac...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Transcriptional and Epigenetic Control of Mammalian Olfactory Epithelium Development
AbstractThe postnatal mammalian olfactory epithelium (OE) represents a major aspect of the peripheral olfactory system. It is a pseudostratified tissue that originates from the olfactory placode and is composed of diverse cells, some of which are specialized receptor neurons capable of transducing odorant stimuli to afford the perception of smell (olfaction). The OE is known to offer a tractable miniature model for studying the systematic generation of neurons and glia that typify neural tissue development. During OE development, stem/progenitor cells that will become olfactory sensory neurons and/or non-neuronal cell type...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

N -palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice
AbstractParkinson ’s disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD ind uced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model. Male CD mice (21 months of age) were pre-treated for 60 days with PEAm. After this...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Differential Behavioral and Biochemical Responses to Caffeine in Male and Female Rats from a Validated Model of Attention Deficit and Hyperactivity Disorder
AbstractEpidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3  g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats—SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in ad...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons
In this study, we assessed the potential therapeutic properties of the whole body periodic acceleration (pGz) to ameliorate the pathology observed in cortical neurons from themdx mouse. pGz adds small pulses to the circulation, thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of nitric oxide (NO). We found [Ca2+]i and [Na+]i overload along with reactive oxygen species (ROS) overproduction inmdx neurons and cognitive dysfunction.mdx neurons showed increased activity of superoxide dismutase, glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell...
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...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

A Novel Five-Node Feed-Forward Loop Unravels miRNA-Gene-TF Regulatory Relationships in Ischemic Stroke
AbstractThe complex and interlinked cascade of events regulated by microRNAs (miRNAs), transcription factors (TF), and target genes highlight the multifactorial nature of ischemic stroke pathology. The complexity of ischemic stroke requires a wider assessment than the existing experimental research that deals with only a few regulatory components. Here, we assessed a massive set of genes, miRNAs, and transcription factors to build a miRNA-gene-transcription factor regulatory network to elucidate the underlying post-transcriptional mechanisms in ischemic stroke. Feed-forward loops (three-node, four-node, and novel five-node...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

P2Y 12 but not P2Y 13 Purinergic Receptor Controls Postnatal Rat Retinogenesis In Vivo
AbstractAdenine nucleotides through P2Y1 receptor stimulation are known to control retinal progenitor cell (RPC) proliferation by modulating expression of the p57KIP2, a cell cycle regulator. However, the role of Gi protein-coupled P2Y12 and P2Y13 receptors also activated by adenine nucleotides in RPC proliferation is still unknown. Gene expression of the purinergic P2Y12 subtype was detected in rat retina during early postnatal days (P0 to P5), while expression levels of P2Y13 were low. Immunohistochemistry assays performed with rat retina on P3 revealed P2Y12 receptor expression in both Ki-67-positive cells in the neurob...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie
AbstractThe analysis of the cerebrospinal fluid (CSF) biomarkers in patients with suspected prion diseases became a useful tool in diagnostic routine. Prion diseases can only be identified at clinical stages when the disease already spread throughout the brain and massive neuronal damage occurs. Consequently, the accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical and clinical naturally occurring scrapie. While decreased total prion protein (PrP) levels and positive PrP seeding activity were already detectable at pre...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

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

Deficiency of Tenascin-C Alleviates Neuronal Apoptosis and Neuroinflammation After Experimental Subarachnoid Hemorrhage in Mice
This study first provided the direct evidence that TNC causes post-SAH neuronal apoptosis and neuroinflammation, potentially leading to the development of a new molecular targeted therapy against EBI. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Role of Chimeric Antigen Receptor T Cell Therapy in Glioblastoma Multiforme
AbstractGlioblastoma multiforme (GBM) is the most common primary malignant cancer of brain, which is extremely aggressive and carries a dreadful prognosis. Current treatment protocol runs around radiotherapy, surgical resection, and temozolomide with median overall survival of around 12 –15 months. Due to its heterogeneity and mutational load, immunotherapy with chimeric antigen receptor (CAR) T cell therapy can be a promising treatment option for recurrent glioblastoma. Initial phase 1 studies have shown that this therapy is safe without dose-limiting side effects and it also h as a better clinical outcome. The...
Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research

Correction to: Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment
The authors declare that the original version of this article contained a mistake in the data of the Figure 2, particularly in the LTP data. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - September 3, 2018 Category: Neurology Source Type: research

Correction to: Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice
The original version of this article unfortunately contained mistake in its Funding inforation. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - September 3, 2018 Category: Neurology Source Type: research

Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Machado-Joseph Disease
AbstractSpinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis. Here, we asked whether citalopram treatment initiated at a post-symptomatic age would still show efficacy. We used a cohort of CMVMJD135 mice that shows increased phenotypic severity and faster disease progression (CMVMJD135hi) compared ...
Source: Molecular Neurobiology - September 1, 2018 Category: Neurology Source Type: research

Early-Life Adversity Induces Epigenetically Regulated Changes in Hippocampal Dopaminergic Molecular Pathways
AbstractEarly-life adversity (ELA) represents a major risk factor for the development of behavioral dysfunctions and mental disorders later in life. On the other hand, dependent on type, time point, and duration, ELA exposure can also induce adaptations, which result in better stress coping and resilience later in life. Guided by the hypothesis that chronic exposure to ELA results in dysfunctional brain and behavior, whereas short exposure to ELA may result in resilience, the behavioral and neurobiological consequences of long-term separation stress (LTSS) and short-term separation stress (STSS) were compared in a mouse mo...
Source: Molecular Neurobiology - September 1, 2018 Category: Neurology Source Type: research

Correction to: Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder
The original version of this article unfortunately contained mistake in its Funding inforation. That is, the Grant Number has an error currently read as “This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 20, 2018 Category: Neurology Source Type: research

IVIG Delays Onset in a Mouse Model of Gerstmann-Str äussler-Scheinker Disease
In this study, we used Gerstmann-Sträussler-Scheinker (GSS)-Tg (PrP-A116V) transgenic mice to test IVIG efficacy since amyloid plaque formation played an important role in GSS pathogenesis. H ere, we provided strong evidence that demonstrates how IVIG could significantly delay disease onset, elongate survival, and improve clinical phenotype in Tg (PrP-A116V) mice. Additionally, in treated animals, IVIG could markedly inhibit PrP amyloid plaque formation and attenuate neuronal apoptosis a t the age of 120 days in mice. Our results indicate that IVIG may be a potential, effective therapeutic treatment for GSS and o...
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice
This study may provide an impetus for development of therapeutics targeting BBB damage in diabetes. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Resveratrol as a Therapy to Restore Neurogliogenesis of Neural Progenitor Cells Infected by Toxoplasma gondii
AbstractThe intracellular protozoanToxoplasma gondii may cause congenital toxoplasmosis and serious brain damage in fetus. However, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains unclear. For this study, neural progenitor cells (NPCs) were obtained from embryo telencephalons (embryonic day 13) and induced to proliferation in the presence of growth factors (GFs). For gathering insights into the biological effects of resveratrol (RSV) on neurogenesis, this study aimed to investigate effects of RSV concentrations (0.1 to 100  μM) on proliferation, migration and differentiation of NPCs inf...
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Correction to: Growth Factors and Neuroglobin in Astrocyte Protection Against Neurodegeneration and Oxidative Stress
The original version of this article unfortunately contained a typo error. The name of author “Ghulam Md Ashrad” should be written as “Ghulam Md Ashraf”. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - July 19, 2018 Category: Neurology Source Type: research

Dehydroepiandrosterone Induces Temozolomide Resistance Through Modulating Phosphorylation and Acetylation of Sp1 in Glioblastoma
AbstractGlioblastoma is the most malignant type of brain tumor for which there are currently no effective treatments. Patient prognosis is improved by radiation combined with temozolomide (TMZ) therapy but only for a short period of time due to the high prevalence of recurrence. Although O6-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair is a well-defined characteristic of TMZ resistance, the mechanism by which MGMT-deficient glioblastoma counteracts TMZ-induced DNA damage, leading to apoptosis, still remains unclear. Previously, we determined that aberrantly activated cytochrome P450 17A1 causes TMZ resista...
Source: Molecular Neurobiology - July 18, 2018 Category: Neurology Source Type: research