Neuroscience
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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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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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Depression and anxiety are common comorbid disorders observed in patients with inflammatory bowel disease (IBD). Increasing line of evidence indicates that immune-inflammatory responses are involved in co-occurrence of mood disorders and IBD. However, the mechanisms through which immune-inflammatory pathways modulate this comorbidity are not yet understood. ⋯ Our results showed that DNBS-induced colonic inflammatory responses were accompanied by infiltration of inflammatory cells, and increased expression of genes involved in toll-like receptor signaling pathway in intestinal tissue. Furthermore, the DNBS-treated mice showed depressive- and anxiety-like behaviors which were associated with increased expression of the inflammatory genes and abnormal mitochondrial function in the hippocampus. These results suggest that peripheral inflammation is able to increase the transcriptional level of the genes in toll-like receptor pathway, induces abnormal mitochondrial function in the hippocampus, and these negative effects may be involved in the co-occurrence of anxiety and depression in early stages of CD.
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Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mice respond to a small set of odorous compounds, including given dimethylpyrazines present in mouse urine. Consequently, mouse pups living in murine colonies are presumably commonly exposed to such GG-activating substances. Since stimulation of the GG elicits alarm and stress reactions in mice, the question arises whether such a GG activation potentially inducing stress could be reduced when pups might rather feel secure in the presence of their mother. ⋯ The attenuated chemosensory responses of GG neurons at 35 °C coincided with a reduced dimethylpyrazine-evoked activation of the glomeruli in the olfactory bulb innervated by GG neurons. The reduction in dimethylpyrazine-evoked GG responses by warm temperatures was positively correlated with exposure time, suggesting that warm temperatures might enhance desensitization processes in GG neurons. In summary, the findings indicate that warm temperatures similar to those in mouse nests in the presence of the dam attenuate GG activation by colony-derived odorants.
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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.