We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior. Pharmacologically, modulating histone acetylation with acetyl-L-carnitine (LAC) or acetyl-N-cysteine (NAC) rapidly increases xCT and activates a network with mGlu2 receptors to prime an enhanced glutamate homeostasis that promotes both pro-resilient and antidepressant-like responses. Pharmacological xCT blockage counteracts NAC prophylactic effects. GFAP-Cre-dependent overexpression of xCT in vDG mimics pharmacological actions in promoting resilience. This work establishes a mechanism by which vDG protection leads to stress resilience and antidepressant responses via epigenetic programming of an xCT-mGlu2 network.

The adult brain is capable of adapting to internal and external stressors by undergoing structural plasticity, and failure to be resilient and preserve normal structure and function is likely to contribute to depression and anxiety disorders. While the hippocampus has provided the gateway for understanding stress effects on the brain, less is known about the amygdala, a key brain area involved in the neural circuitry of fear and anxiety. Here, in mice more vulnerable to stressors, we demonstrate structural plasticity within the medial and basolateral regions of the amygdala in response to prolonged 21day chronic restraint stress (CRS). Three days before the end of CRS, treatment with the putative, rapidly acting antidepressant, acetyl-L-carnitine (LAC) in the drinking water opposed the direction of these changes. Behaviorally, the LAC treatment during the last part of CRS enhanced resilience, opposing the effects of CRS, as shown by an increased social interaction and reduced passive behavior in a forced swim test. Furthermore, CRS mice treated with LAC show resilience of the CRS-induced structural remodeling of medial amygdala (MeA) stellate neurons. Within the basolateral (BLA) amygdala, LAC did not reduce, but slightly enhanced, the CRS-increased length and number of intersections of pyramidal neurons. No structural changes were observed in MeA bipolar neurons, BLA stellate neurons, or in lateral amygdala (LA) stellate neurons. Our findings identify MeA stellate neurons as an important component in the responses to stress and LAC action and show that LAC can promote structural plasticity of the MeA. This may be useful as a model for increasing resilience to stressors in at risk populations.

Objectives To determine whether steroids are effective in treating adults with acute vestibular neuritis. Data Sources PubMed, Embase, CINAHL, Cochrane CENTRAL, Web of Science, CAB Abstract, ICTRP, LILACS, PEDRO, ClinicalTrials.Gov, Google Scholar, NARIC, and OT Seeker. Review Methods A systematic review was undertaken for articles reporting subjective and/or objective outcomes of corticosteroids in adults with acute vestibular neuritis between December 2010 and October 2019. Reports of patient recovery from clinical vestibular outcomes at various time points and adverse effects from corticosteroids were of interest. Statistical analysis included qualitative and quantitative assessments. A limited meta-analysis of the data was performed through a random effects model. Results Eight studies met the criteria, and 6 were included in the meta-analysis. No significant differences between the groups (corticosteroid vs placebo, corticosteroid vs vestibular exercise, or corticosteroid vs combination of vestibular exercise and corticosteroid) were reported in the proportion of patients with complete recovery at 1, 6, and 12 months. The corticosteroid group had significantly better caloric recover at 1 month (95% CI, –16.33 to –0.32); however, there was no significant difference to the overall effect between the groups across 12 months. Subjective recovery did not differ between the groups. Five of the 8 studies reported on adverse effects from corticosteroids. Conclusion There is insufficient evidence to support the use of corticosteroids in managing acute vestibular neuritis in adults. At present, corticosteroids appear to have short-term benefits in canal paresis but no long-term benefits in canal paresis and symptomatic recovery. Future studies should consider including a wider variety of clinical vestibular tests and frequent acute follow-ups to monitor the effects of corticosteroids.

This study suggests that ISB in the geriatric population is associated with a history of right frontal lobe stroke and with severity of dementia. Case examples of pharmacologic interventions are reviewed.