Neuroscience
-
Hypoxic-ischemic brain damage (HIBD) usually induces chronic neurological disorder and even acute death, but effective neuroprotective strategy is still limited. Herein, we performed this study to clarify the mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) containing microRNA-93 (miR-93) in influencing this damage via regulation of the histone deacetylase 4 (HDAC4)/B-cell lymphoma-2 (Bcl-2) axis. Initially, differentially expressed Bcl-2 was identified in middle cerebral artery occlusion (MCAO), and the upstream regulatory miR-93 and its potential target HDAC4 were also predicted through bioinformatics analysis. ⋯ Of note, miR-93 was found to target HDAC4. Importantly, MSC-derived EVs overexpressing miR-93 suppressed HDAC4 expression and subsequently impeded the apoptosis of OGD-exposed hippocampal neurons in vitro, and also ameliorated HIBD in vivo. Taken together, miR-93 delivered by MSC-derived EVs can ameliorate HIBD by suppressing hippocampal neuron apoptosis through targeting the HDAC4/Bcl-2 axis, a finding which may be of great significance in the treatment of HIBD.
-
Despite the presence of multiple pharmacotherapeutic options, incidence rates for depressive disorders continue to rise. Nonpharmacological approaches (e.g., cognitive and behavioral therapies) exhibit encouraging efficacy rates; however, a lack of preclinical models has prevented progress in the identification of relevant neurobiological mechanisms of these approaches. Accordingly, the effort-based reward (EBR) preclinical model exposes rats to response-outcome (R-O) contingencies and provides an opportunity to investigate behavioral clinical approaches. ⋯ Examination of brain-derived neurotrophic factor (BDNF) in the lateral habenula (LHb), a putative neurobiological target for depressive symptoms, revealed lower BDNF immunoreactivity in EBR contingent-trained rats. Females in both training groups exhibited higher dehydroepiandrosterone/cortisol (DHEA/CORT) ratios, suggesting, along with the increased engagement with novel stimulus panels, that female rats may be more responsive to EBR contingency training than males. Together, these results suggest that EBR contingency training offers promise as a preclinical rat model for behavioral therapeutic interventions for depressive symptoms leading to a clearer understanding of putative neurobiological mechanisms.
-
Knockdown of Girdin induced apoptosis of glioblastoma cells via the mitochondrion signaling pathway.
Glioblastoma is the most common primary brain tumor with poor survival rate and without effective treatment strategy. However, the influence of Girdin on human glioblastoma and the underlying molecular mechanisms have yet to be uncovered. We mainly investigated the role of Girdin in glioblastoma cells apoptosis. ⋯ Moreover, subcutaneous mouse xenograft model was used to validate the role of Girdin in glioblastoma apoptosis. Consistently, in vivo assays showed that knockdown of Girdin inhibited the growth of the grafted tumor and increased the level of Cyt-C and Bad. These findings demonstrated that knockdown of Girdin may induce Bad expression and reduce Bcl-2 expression by inhibiting the activation of AKT, leading to the release of Cyt-C from mitochondria, thereby promoting glioblastoma cells apoptosis.
-
Long non-coding RNA H19 (lncRNA H19) is transcribed from the H19 gene. We previously reported the role of lncRNA H19 in the pathogenesis of cerebral ischemic stroke. The present study aimed to elucidate the relationship between lncRNA H19 and blood-brain barrier breakdown induced by cerebral ischemic stroke. ⋯ Inhibition of neuronal exosomal lncRNA H19 regulated astrocytic microRNA (miR)-18a and vascular endothelial growth factor (VEGF) expression. Further, lncRNA H19 induced a decrease in tight junction proteins expression via the lncRNA H19/miR-18a/VEGF axis. This study highlights the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and blood-brain barrier breakdown.
-
Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. ⋯ CBD significantly dampens microglial migration and accumulation to the hippocampus. While long term artisanal CBD use does not prevent or lessen seizure severity, CBD is a promising adjunctive partner for its ability to depress epileptogenic processes. These studies indicate that artisanal CBD is beneficial as it both decreases inflammation in the CNS and reduces the number of ectopic neurons deposited in the hippocampal area post seizure.