Neuroscience
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Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease. The purpose of this study was to investigate the link between microbiota composition in important mucosal interfaces (oral, nasal, and intestinal) and PD. Sequencing was undertaken of the V4-V5 region of the 16S ribosomal RNA (rRNA) gene of the microbiome from the oral cavity, nasal cavity, and gut of 91 PD patients and 91 healthy controls. ⋯ Changes in these pathways can influence metabolism and inflammation, thereby contributing to PD pathogenesis. In addition, several subnetworks containing differentially abundant microbiota in the oral cavity and gut samples from PD patients may regulate microbial composition and function in PD. Overall, our results indicate that oral and gut dysbiosis may affect PD progression and provide a basis for understanding the pathogenesis of PD and identifying potential therapeutic targets for the treatment of this disease.
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The prospect of exploiting memory reconsolidation to treat mental health disorders has received great research interest, particularly following demonstrations that the β-adrenergic receptor antagonist propranolol, which is safe for use in humans, can disrupt the reconsolidation of pavlovian conditioned fear memories. However, recent studies have failed to replicate the effects of propranolol on fear memory reconsolidation, and have questioned whether treatments based upon reconsolidation blockade would be robust enough for clinical translation. It remains possible, though, that studies reporting no effect of propranolol on memory reconsolidation could be due to a failure to engage the memory destabilisation process, which is necessary for the memory to become susceptible to disruption with amnestic agents. ⋯ Following a failure to replicate, we manipulated the parameters of the memory reactivation session to enhance prediction error in an attempt to overcome the boundary conditions of reconsolidation. On finding no disruption of memory despite these manipulations, we examined the expression of the post-synaptic density protein Shank in the basolateral amygdala. Degradation of Shank has been shown to correlate with the induction of memory lability, but we found no effect on Shank expression, consistent with the lack of observed behavioural effects.
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Microglia cells are activated after cerebral ischemia-reperfusion injury (CIRI), playing a dual role in aggravating the injury or promoting tissue repair by polarization. Translocator protein (TSPO) is a biomarker of neuroinflammation or microglia activation. Its expression is significantly increased while brain injury and neuroinflammation occur. ⋯ In vitro studies showed that shRNA-mediated TSPO knock-down promoted M1 polarization but inhibited M2 polarization, accompanied by a significant decrease in cell viability. On the contrary, overexpression of TSPO inhibited M1 polarization, promoted M2 polarization, and significantly improved cell viability. In summary, TSPO plays a neuroprotective role in CIRI by inhibiting M1 polarization and promoting M2 polarization, which suggests that TSPO may have the potential to serve as a therapeutic target for stroke.
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Therapeutic hypothermia with modest results is the only treatment currently available for neonatal hypoxic ischemic encephalopathy (HIE). Endothelin B (ETB) receptors in the brain are shown to have neural restorative capacity. ETB receptors agonist sovateltide alone or as an adjuvant therapy may enhance neurovascular remodeling in HIE. ⋯ Animals receiving sovateltide demonstrated a significant (p < 0.0001) upregulation of ETB receptor, VEGF, and NGF expression in the brain compared to vehicle-treated animals. Additionally, sovateltide alone or in combination with therapeutic hypothermia significantly (p < 0.001) reduced cell death when compared to vehicle or therapeutic hypothermia alone, demonstrating that sovateltide is neuroprotective and attenuates neural damage following HIE. These findings are important and merit additional studies for development of new interventions for improving neurodevelopmental outcomes after HIE.
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Affective disorders (i.e. anxiety and depression) are commonly observed in patients with epilepsy and induce seizure aggravation. Animal models of epilepsy that exhibit affective disorder features are essential in developing new neuromodulatory treatments. GEAS-W rats (Generalized Epilepsy with Absence Seizures, Wistar background) are an inbred model of generalized epilepsy showing spontaneous spike-wave discharges concomitant with immobility. ⋯ We observed a main effect of treatment and a significant treatment by strain interaction on anxiety-like and depressive-like behaviours, with active-tDCS GEAS-W rats entering the center of the open field more often and showing less immobility in the forced swimming test. Furthermore, there was a main effect of treatment on corticosterone with active-tDCS animals showing marked reduction in plasmatic levels. This study described preclinical evidence to support tDCS treatment of affective disorders in epilepsy and highlights corticosterone as a possible mechanism of action.