Cortistatin (CORT) is a neuropeptide with neuronal depressant and sleep-modulating properties that acts as a ligand for the MRGPRX2 receptor on mast cells 1. However, the provided abstracts primarily address corticosterone (also abbreviated CORT), the glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal (HPA) axis, which is distinct from the cortistatin neuropeptide. Corticosterone functions as a systemic intercellular signal whose levels vary circadianly and increase with environmental stressors 2. It activates mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in a complementary manner to promote stress resilience and homeostatic recovery 3. These receptors mediate both rapid non-genomic and slower gene-mediated mechanisms that are time-dependent and sexually dimorphic 3. Chr1 elevated corticosterone impairs adult hippocampal neurogenesis by inducing hyperactive neuronal autophagy that depletes brain-derived neurotrophic factor (BDNF), contributing to depressive-like behaviors 4. It also dysregulates serotonergic neuron-astrocyte signaling in the medial prefrontal cortex 5. Chr1 corticosterone exposure triggers multiple pathological mechanisms including neuroinflammation, oxidative stress, and altered microRNA expression patterns 67. Additionally, corticosterone mediates dual pro- and anti-inflammatory effects through widespread glucocorticoid receptor expression 8.