Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

Abstract

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Axis Activation Model in Stress Induced Genesis of Psychiatric Disorders

“…Hippocampal inhibitory control of HPA axis activity, which is a normal phenomenon in homeostasis, is also known to be compromised in chronic restraint stress (115,121); and along with glucocorticoids, NGFs are known to be central players causing this dysregulation (109,112,122). Hippocampal pyramidal neurons secrete NGFs in response to stress which correspond to HPA axis activity (123,124), and also TrkB, the receptor for BDNF is found to be co-localized with glucocorticoid receptor (GR) and having mutual influence on each other's signalling in these neurons (122).…”

“…Hippocampal pyramidal neurons secrete NGFs in response to stress which correspond to HPA axis activity (123,124), and also TrkB, the receptor for BDNF is found to be co-localized with glucocorticoid receptor (GR) and having mutual influence on each other's signalling in these neurons (122). A study by Lambert et al has shown in primary rat cortical neurons that BDNF induces structural change at GR gene (phosphorylation at serine 155 and 287) and causes significant change in its transcriptome (125).…”

Attachment Figure's Regulation of Infant Brain and Behavior

“…Convergence of research results across rodents and humans has been reviewed elsewhere and I highlight a few reviews, although many other excellent reviews are available (Branchi & Cirulli, 2014;CadizMoretti, Otero-Garcia, Martinez-Garcia, & Lanuza, 2014;Callaghan & Tottenham, 2016;Chen & Baram, 2016;Daskalakis, De Kloet, Yehuda, Malaspina, & Kranz, 2015;Davis & Pfaff, 2014;Gee & Casey, 2015;Molet, Maras, Avishai-Eliner, & Baram, 2014;Patchev, Rodrigues, Sousa, Spengler, & Almeida, 2014;Rincon-Cortes & Sullivan, 2014;Tang, ReebSutherland, Romeo, & McEwen, 2014;Tost, Champagne, & Meyer-Lindenberg, 2015;Turecki & Meaney, 2016).…”

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Adrenal Axis Dysregulation Model in Stress Induced Genesis of Psychiatric Disorders

“…Hippocampal inhibitory control of HPA axis activity, which is a normal phenomenon in homeostasis, is also known to be compromised in chronic restraint stress (116,122); and along with glucocorticoids, NGFs are known to be central players causing this dysregulation (109,112,123). Hippocampal pyramidal neurons secrete NGFs in response to stress which correspond to HPA axis activity (124,125), and also TrkB, the receptor for BDNF is found to be co-localized with glucocorticoid receptor (GR) and having mutual influence on each other's signalling in these neurons (123).…”