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Adolescence is a critical neurodevelopmental period characterized by heightened neuroplasticity. While the acute effects of binge ethanol (EtOH) consumption are documented, its long-term impact on both pain sensitivity and microglial activation during adolescence remains unclear. Given serotonin's (5-HT) known involvement in pain processing and sensitivity to EtOH, this study examined the effects of adolescent EtOH binge on microglia-induced neuroinflammation in serotonergic nuclei, downstream 5-HT signaling, and pain sensitivity at different time points after EtOH withdrawal. Adolescent male C57BL/6J mice received triweekly oral gavage of 20 % EtOH or water for 4 weeks and were assessed after 24 h and 3 weeks post-withdrawal. We used immunohistochemistry to assess neuroinflammation in the dorsal raphe, median raphe, and raphe magnus by labeling 5-HT, CD68, and P2Y12. Further analyses examined downstream signaling via 5-HT and serotonin transporter (SERT) expression in the nucleus accumbens, anterior cingulate cortex, thalamus, amygdala, hypothalamus, and raphe magnus. Pain sensitivity was then assessed using the Hargreaves test. EtOH exposure led to widespread serotonergic and neuroinflammatory changes. Significant increases in microglia-induced neuroinflammation were observed in the dorsal raphe nucleus, median raphe nucleus, and raphe magnus nucleus after both 24 h and 3 weeks post-withdrawal, along with significant deficits in 5-HT. Similar 5-HT deficits were observed in downstream regions—notably in the anterior cingulate cortex, thalamus, amygdala, and hypothalamus—at varying time points post-withdrawal. EtOH-exposed mice also showed lasting hyperalgesia at both 24 h and 3 weeks post-withdrawal that persisted for up to 9 weeks. These results suggest that persistent hyperalgesia following adolescent EtOH binge may be driven by changes in serotonergic function and microglial activation. [Display omitted] •Adolescent ethanol binge induced lasting thermal hyperalgesia in male mice.•Increased neuroinflammation in DRN, MRN, and RMg after EtOH withdrawal.•Persistent 5-HT deficits in raphe nuclei and downstream pain-related regions.

None of the members of UI-FT worked in the office when the law was passed, and while team members can guess that the response was likely largely focused on regulatory compliance, they do not know for sure. Robust collaboration with General Counsel, Information Technology, the Dean of Students Office, the Institutional Review Board, and many collegiate and departmental offices support endeavors outside the realm of their expertise or comfort level. When UI-FT was first exploring areas to address related to FERPA, including training, breach response, accountability, compliance, and inquiry, team members realized that most folks want to preserve student privacy, data integrity, and the spirit of FERPA. Each new year, employees with designated human resource codes requiring the adherence to FERPA must check a box to acknowledge their responsibility to uphold the regulation, but it does not provide further information.

Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy characterized by sensory dysfunction and muscle weakness, manifesting in the most distal limbs first and progressing more proximal. Over a hundred genes are currently linked to CMT with enrichment for activities in myelination, axon transport, and protein synthesis. Mutations in tRNA synthetases cause dominantly inherited forms of CMT and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. Rescuing protein synthesis in CMT mutant neurons could offer exciting therapeutic options beyond symptom management. To address this need, we expressed CMT-linked variants in tyrosyl tRNA synthetase (YARS-CMT) in primary sensory neurons and evaluated impacts on protein synthesis and cell viability. YARS-CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death. To determine how YARS-CMT expression affects axon outgrowth, we dissociated and replated these neurons to stimulate axon regeneration. To our surprise, axonal regrowth occurred normally in replated YARS-CMT neurons. Moreover, replating YARS-CMT neurons rescued protein synthesis. Inhibiting mTOR suppressed rescue of protein synthesis after replating, consistent with its significant role in protein synthesis during axon regeneration. These discoveries identify new avenues for augmenting protein synthesis in diseased neurons and restoring protein synthesis in CMT or other neurological disorders.

Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD. Highlights Neuromodulatory subcortical systems are uniquely vulnerable in Alzheimer's disease. Biological sex is an important factor that modulates dementia risk and progression. Neuromodulatory subcortical systems show sex differences in structure and function. Sex‐dependent neuromodulatory nuclei dysfunction in dementia is understudied.