Stress Leads to Contrasting Effects on the Levels of Brain Derived Neurotrophic Factor in the Hippocampus and Amygdala

Abstract

Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2h/day) causes growth of dendrites and spines in the basolateral amygdala (BLA), but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity- BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2h) leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

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

“…For example, prefrontal cortex and hippocampus are known to inhibit but amygdala excites it (115). In the similar context, chronic immobilization stress in male rats was observed to produce inverse neuronal BDNF secretion and hence growth changes mediated by it, in hippocampus and amygdala (116).…”

Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex

“…Indeed, the dentate gyrus undergoes reduced cell number under chronic stress (Pham et al, 2003) and in response to corticosterone levels (Sousa et al, 1999), whereas physical activity and an enriched environment increase dentate gyrus volume and neuron number (Kempermann et al, 1997;van Praag et al, 1999). Hippocampal neurogenesis has also been linked to BDNF levels, which are highly dynamic in response to chronic stress, where initial decreases have been observed (Smith et al, 1995), but with recovery after stress can return to baseline (Lakshminarasimhan and Chattarji, 2012). And direct infusion of BDNF has been shown to increase hippocampal neurogenesis (Scharfman et al, 2005).…”

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

“…NGFs show activity and stress based synthesis in various brain regions involved in stress response regulation (1,105,115) and the involved brain regions are known to differentially regulate HPA axis. For example, prefrontal cortex and hippocampus are known to inhibit but amygdala excites it (116). Additionally, chronic immobilization stress in male rats was observed to produce inverse neuronal BDNF secretion and hence growth changes mediated by it, in hippocampus and amygdala (117).…”

“…Differential regulation of HPA axis by various brain regions involved in stress response regulation is presumably the reason of phenotypic diversity observed in psychiatric disorders (116,118).…”

“…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).…”