Neuroscience
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In the United States, approximately 90% of alcohol consumed by adolescents is binge drinking. Binge-like ethanol exposure during adolescence promotes dysregulation of neurotrophic responses and neurogenesis in the hippocampus. These effects include changes in proliferation, regulation, differentiation, and maturation of neurons, and there is indication that such effects may be disproportionate between sexes. ⋯ Altogether, our findings indicate that although AIE did not have a persistent effect on hippocampal neurotrophic levels, there was still a reduction in neurogenesis. The neurogenic impairment was not sex specific, but the neurogenic deficits in males may be attributed to an increase in pro-inflammatory cytokine expression. A persistent impairment in neurogenesis may have an impact on both behavioral maladaptations and neurodegeneration in adulthood.
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A mother's exposure to immune challenge during pregnancy is well known to be a detrimental factor to the development of the offspring's brain and an impetus for neuropsychiatric disorders. Previous studies have shown that these adverse events can dysregulate the stress response machinery. Two crucial components of the stress axis considered to be affected have been targets in these studies: the glucocorticoid receptor (GR), and FKBP5 which regulates GR activity. ⋯ RT-qPCR analysis of MIA's effect on GR yielded insignificant results. However, we found that EE increased GR expression in the medial preoptic area which could be indicative of a positive regulation by EE. This study provides evidence of the impact of both gestational insult and EE on the regulation of stress responsive genes in the developing brain.
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Sleep loss, either induced by obstructive sleep apnea or other forms of sleep dysfunction, induces an inflammatory response, as commonly measured by increased circulating levels of pro-inflammatory cytokines. Increased catecholamines from sympathetic nervous system (SNS) activation regulates this peripheral inflammation. However, the role that catecholamines play in mediating neuroinflammation from sleep perturbations is undescribed. ⋯ Effects of chronic SF were more pronounced than acute SF, and 1 week of recovery was not sufficient to alleviate neuroinflammation. Importantly, 6-OHDA treatment significantly alleviated SF-induced inflammation and microglial responses. This study provides evidence of SNS regulation of neural inflammation from SF, suggesting a potential role for therapeutics that could mitigate neuroinflammatory responses to sleep dysfunction.
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Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). ⋯ In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases.
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Genetic analyses have linked BTBD9 to restless legs syndrome (RLS) and sleep regulation. Btbd9 knockout mice show RLS-like motor restlessness. Previously, we found hyperactivity of cerebellar Purkinje cells (PCs) in Btbd9 knockout mice, which may contribute to the motor restlessness observed. ⋯ However, Syngap1 heterozygous knockout mice showed nocturnal, instead of diurnal, motor restlessness. Our results suggest that SYNGAP1 deficiency may not contribute directly to the RLS-like motor restlessness observed in Btbd9 knockout mice. Finally, we found that PC-specific Btbd9 knockout mice exhibited deficits in motor coordination and balance similar to Btbd9 knockout mice, suggesting that the motor effect of BTBD9 in PCs is cell-autonomous.