Neuroscience
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Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. ⋯ Importantly, they also reversed the locomotor deficit caused by prior exposure to 6-OHDA; rasagiline also reversed neuronal loss and minocycline partially restored neuronal loss due to prior 6-OHDA, making them candidates for investigation as neuro-restorative treatments for Parkinson's disease. Our findings in zebrafish reflect preliminary clinical findings for rasagiline and minocycline. Thus, we have developed a zebrafish model suitable for high-throughput screening of putative neuroprotective and neuro-restorative therapies for the treatment of Parkinson's disease.
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The assessment of binge ethanol-induced neuronal activation, using c-Fos immunoreactivity (IR) as a marker of neuronal activity, is typically accomplished via forced ethanol exposure, such as intraperitoneal injection or gavage. Neuronal activity using a voluntary binge-like drinking model, such as "drinking-in-the-dark" (DID), has not been thoroughly explored. Additionally, studies assessing ethanol-elicited neuronal activation may or may not involve stereotaxic surgery, which could impact c-Fos IR. ⋯ Relative to water-consuming controls, mice with BECs ≥ 80 mg/dl showed significantly elevated c-Fos IR in several brain regions implicated in neurobiological responses to ethanol. In general, the brain regions exhibiting binge-induced c-Fos IR were the same between studies, though differences were noted, highlighting the need for caution when interpreting ethanol-induced c-Fos IR when subjects have a prior history of surgery. Altogether, these results provide insight into the brain regions that modulate binge-like ethanol intake stemming from DID procedures among animals with and without surgery experience.
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Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18-35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. ⋯ The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex.
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The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. ⋯ Furthermore, the anterodorsal and paratenial thalamic nucleus received innervation from PV-positive neurons in the TRNrd. They were specifically inhibited by GABA, which is released from local axonal endings of PV neurons. These findings indicate that activation of PV neurons in the TRNrd increases pain sensitivity in PV-Cre transgenic mice.
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In this paper, by utilizing surface diffeomorphic deformations, we constructed and analyzed subcortical shape morphometric networks in 210 healthy control (HC) subjects and 175 subjects with Alzheimer's disease (AD), aiming to identify AD-induced abnormalities in the subcortical shape network. We quantitatively analyzed pertinent network attributes of the entire network and each node. Further to this, hierarchical analyses were performed; group comparisons were conducted at the structure level first and then the sub-region level. ⋯ In addition, the local nodal efficiencies between the right thalamus and all three of the right hippocampus, right amygdala, and left thalamus, as well as that between the left amygdala and left hippocampus, decreased significantly in AD. According to the sub-regional network analyses, we observed significant AD-induced local efficiency decreases between different sub-regions within the right hippocampus itself and between the subiculum of the right hippocampus and the sub-region of the right thalamus connecting to the temporal lobe, indicating a degradation of circuit between the hippocampus, thalamus, and temporal lobe. Statistical comparisons were performed using 40,000 non-parametric permutation tests, with false discovery rate correction employed for multiple comparison correction.