👤 Probir Chakravarty

Following their engagement towards differentiation, tissue stem cells often transit through a precursor state that is difficult to define because of its transient nature; similarly, the precise role of lineage precursors in implementation of tissue architecture and function is unknown. In the present work, we used two mouse models of deficient feedback regulation to characterize precursors of the pituitary corticotrope lineage that regulates the stress response. Both the POMC knockout and adrenalectomized mouse models develop glucocorticoid deficiency and compensatory accumulation of corticotrope precursors that have so far eluded characterization. We found that pre-corticotrope differentiation depends on the lineage-specific factor Tpit and is repressed by glucocorticoids. We identified brain-derived neurotrophic factor (BDNF) as the signal that engages pituitary stem cells towards differentiation in these models as well as in normal pituitary development. A glucocorticoid-sensitive BDNF autocrine loop active in pre-corticotropes turns these cells into signaling hubs for maintenance of pituitary-adrenal homeostasis. Pituitary lineage precursors expand in conditions of deficient feedback regulationBDNF mobilizes pituitary stem cells during establishment of tissue size and architectureCorticotrope precursors are a signaling hub for tissue homeostasis. Show less

Vicarious trauma, the psychological distress from witnessing others' suffering, is an increasingly recognized precursor to depression and anxiety. However, the underlying neurobiological mechanisms remain poorly understood and appear to be sex-dependent. This study investigated the behavioral, physiological, and molecular consequences of purely psychological stress using a novel rodent model of vicarious learned helplessness (VLH). Male and female C57BL/6J mice were used to establish VLH paradigm. Observer mice witnessed conspecifics receiving inescapable foot shocks through a partitioned chamber allowing multisensory interaction. Following 7 days of conditioning, behavioral assays assessed anxiety and depressive symptoms. Prefrontal cortex tissue was analyzed using RT-qPCR and immunoblotting to identify molecular alterations. Vicarious stress induced depression phenotype in both sexes, characterized by active avoidance deficits, anhedonia and anxiety, comparable to direct physical trauma. Physiological assessments revealed hypothalamic-pituitary-adrenal (HPA) axis hyperactivity with elevated plasma corticosterone in both sexes. While molecular analysis showed shared downregulation of metabotropic glutamate receptor 2 (mGluR2) and elevated Il6 mRNA in the prefrontal cortex, distinct sexual dimorphism emerged. Males displayed specific deficits in neurotrophic support ( Vicarious trauma is sufficient to drive depression-like pathology through distinct molecular trajectories in males and females. These findings are suggestive of the critical necessity for sex-specific therapeutic strategies when treating trauma-related psychiatric disorders. Show less

DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of Show less