AUTHOR=Kovács László Ákos , Füredi Nóra , Ujvári Balázs , Golgol Abolfazl , Gaszner Balázs 

TITLE=Age-Dependent FOSB/ΔFOSB Response to Acute and Chronic Stress in the Extended Amygdala, Hypothalamic Paraventricular, Habenular, Centrally-Projecting Edinger-Westphal, and Dorsal Raphe Nuclei in Male Rats

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.862098

DOI=10.3389/fnagi.2022.862098

ISSN=1663-4365

ABSTRACT=FOS proteins are early responding gene products which contribute to the formation of activator protein-1. Several acute and chronic stimuli lead to Fos gene expression, accompanied by an increase of nuclear FOS, that appears to decline by aging. FOSB is another marker to detect acute cellular response, while ∆FOSB mirrors long-lasting changes in neuronal activity upon chronic stress. The notion that the occurrence of stress-related mood disorders shows some age dependence suggests that the brain’s stress sensitivity is also a function of age. To study age-dependent stress vulnerability at immediate early gene level, we aimed to describe how the course of aging affects the neural responses of FOSB/∆FOSB in the acute restraint stress (ARS), and chronic variable mild stress (CVMS) in male rats.
Fourteen brain areas [central, medial, basolateral (BLA) amygdala; dorsolateral- (BNSTdl), oval- (BNSTov), dorsomedial-, ventral- (BNSTv) and fusiform- (BNSTfu) divisions of the bed nucleus of the stria terminalis; medial and lateral habenula, hypothalamic paraventricular nucleus (PVN), centrally-projecting Edinger-Westphal nucleus, dorsal raphe nucleus, barrel field of somatosensory cortex (S1)] were examined in the course of aging. Eight age groups (1-month-old (M), 1.5M, 2M, 3M, 6M, 12M, 18M, 24M) of rats were exposed to a single ARS versus controls. In addition, rats in six age groups (2M, 3M, 6M, 12M, 18M, 24M) were subjected to CVMS.
The FOSB/∆FOSB immunoreactivity (ir) was a function of age in both control, ARS- and CVMS-exposed rats. ARS increased the FOSB/∆FOSB ir in all nuclei (except in BLA), but only BNSTfu, BNSTv and PVN reacted throughout the examined lifespan. The CVMS did not increase the FOSB/∆FOSB ir in BLA, BNSTov, BNSTdl and S1. PVN showed a constantly maintained FOSB/∆FOSB ir during the examined life-period. The maximum of stress-evoked FOSB/∆FOSB signal was detected at 2M-3M periods in the ARS- and at 6M, 18M in CVMS- model.
Corresponding to our previous observations on FOS, the FOSB/∆FOSB response to stress decreased with age in most of the examined nuclei. Only the PVN exerted a sustained age-independent FOSB/∆FOSB, which may reflect the long-lasting adaptation response and plasticity of neurons that maintain the hypothalamus-pituitary-adrenal axis response throughout the lifespan.