Neuroscience
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Synaptic pruning during adolescence is critical for optimal cognition. The CA3 hippocampus contains unique spine types and plays a pivotal role in pattern separation and seizure generation, where sex differences exist, but adolescent pruning has only been studied in the male. Thus, for the present study we assessed pruning of specific spine types in the CA3 hippocampus during adolescence and investigated a possible mechanism in the female mouse. ⋯ Because our previous findings suggest that pubertal increases in α4βδ GABAA receptors (GABARs) trigger pruning in CA1, we investigated their role in CA3. α4 expression in CA3 hippocampus increased 4-fold at puberty (P < 0.05), assessed by immunostaining and verified electrophysiologically by an increased response to gaboxadol (100 nM), which is selective for α4βδ. Knock-out of α4 prevented the pubertal decrease in kalirin-7 and synaptic pruning and also increased the dendritic length, demonstrating a functional link. These data suggest that pubertal α4βδ GABARs alter dendritic morphology and trigger pruning in female CA3 hippocampus.
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Dopaminergic signaling in the central nervous system regulates several aspects of animal behavior. In the dopaminergic circuits, there are two classes of neurons that can be differentiated by their expression of dopamine receptors, D1 or D2 receptors (D1Rs or D2Rs). Notably, Ca2+-permeable GluA2-lacking glutamate AMPA receptors (CP-AMPARs) are important for gating synaptic plasticity and gene expression in neurons, and their expression particularly in the striatum affects various forms of animal behavior. ⋯ Both D1R and D2R GluA2 KO mice consumed less food compared with control animals, while D1R GluA2 KO animals showed significantly more weight gain. Finally, D1R GluA2 KO induced anti-depressant effects, while GluA2-lacking AMPAR expression in D2R neurons promoted depression-like behavior. Taken together, GluA2-lacking CP-AMPAR expression in D1R and D2R neurons differentially affects animal behavior.
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The present study was designed to use blood-oxygen-level dependent (BOLD) imaging to "fingerprint" the change in activity in response to oxycodone (OXY) in drug naïve rats before and after repeated exposure to OXY. It was hypothesized that repeated exposure to OXY would initiate adaptive changes in brain organization that would be reflected in an altered response to opioid exposure. Male rats exposed to OXY repeatedly showed conditioned place preference, evidence of drug-seeking behavior and putative neuroadaptation. ⋯ In the MEMRI study, rats received OXY treatments (2.5 mg/kg, twice daily) for four consecutive days following intraventricular MnCl2. Under isoflurane anesthesia, T1-weighted images were acquired and subsequently analyzed showing activity in the forebrain limbic system, ventral striatum, accumbens, amygdala and hippocampus. These results show brain activity is markedly different when OXY is presented to drug naïve rats versus rats with prior, repeated exposure to drug.
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The central nervous system (CNS) and gastrointestinal tract (GIT) are linked through neuro-endocrine and humoral pathways. Critically ill patients suffer severe physical and emotional stress and frequently receive acid suppressants; however, stress and acid suppression may alter GIT microbiota. This study evaluated the effects of acid suppression on the GIT microbiota and genome-wide expression of brain-specific genes in a murine model of restraint stress. ⋯ Acute stress has region-specific effects on the distribution of GIT commensal bacteria which is heightened with acid suppression. Several key biological processes in the hippocampus that are needed for neurocognition are affected by dysbiosis caused by acid suppression during stress. Further studies should evaluate associations between microbiota, host gene expression, the abundance of CNS neurocognitive modulators, and their impact on cognition and behavior.
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Sleep disturbances are a common early symptom of neurodegenerative diseases, including Alzheimer's disease (AD) and other age-related dementias, and emerging evidence suggests that poor sleep may be an important contributor to development of amyloid pathology. Of the causes of sleep disturbances, it is estimated that 10-20% of adults in the United States have sleep-disordered breathing (SDB) disorder, with obstructive sleep apnea accounting for the majority of the SBD cases. The clinical and epidemiological data clearly support a link between sleep apnea and AD; yet, almost no experimental research is available exploring the mechanisms associated with this correlative link. ⋯ No effect was found for chronic IH exposure on amyloid-beta levels or plaque load in the APP/PS1 KI mice. A significant increase in GFAP staining was found in the APP/PS1 KI mice following chronic IH exposure, but not in the WT mice. Profiling of genes associated with different phenotypes of astrocyte activation identified GFAP, CXCL10, and Ggta1 as significant responses activated in the APP/PS1 KI mice exposed to chronic IH.