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, 2 h/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, 2 h) 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.

Figure 1. Chronic stress regulates BDNF expression in CA3 and BLA in contrasting manner.

Data are presented as mean ± SEM. A Experimental design of chronic stress (CIS+1d) followed by micro dissection of area CA3 from transverse hippocampal sections or BLA from coronal sections. B BDNF expression in area CA3 is decreased after chronic stress (Control, n = 5; CIS+1d, n = 5), C Chronic stress up regulates BDNF expression in BLA (Control, n = 6; CIS+1d, n = 8). Chronic stress induced changes in BDNF expression profile is normalized to respective control level. D Serum corticosterone levels are up regulated after chronic stress in comparison to controls (Control, n = 5; CIS+1d, n = 6). Significant differences *, p<0.05; Unpaired, two-tailed, Student's t-test was used to compare stress and control groups.

Figure 2. Contrasting profiles of BDNF in CA3 and BLA in response to recovery from chronic stress.

Data are presented as mean ± SEM A Experimental design of 21 days of recovery from chronic stress paradigm (CIS+21d). B BDNF expression in area CA3 comes back to control levels post recovery from chronic stress (Control, n = 6; CIS+21d, n = 6), C Chronic stress induced up regulation in BDNF expression in BLA persists even after twenty one days of recovery (Control, n = 4; CIS+21d, n = 6). BDNF expression profile is normalized to respective control level. D The up regulation of serum corticosterone levels persists even after recovery from chronic stress (Control, n = 7; CIS+21d, n = 6). Significant differences *, p<0.05; Unpaired, two-tailed, Student's t-test was used to compare stress and control groups.

Figure 3. Acute stress modulates BDNF profile differentially in CA3 and BLA.

Data are presented as mean ± SEM. A Experimental design of acute stress (AIS+1d) and recovery for 10 days from acute stress (AIS+10d). B BDNF expression in area CA3 in response to acute stress. Acute stress does not change the BDNF levels in CA3 (Control, n = 9; AIS+1d, n = 9; AIS+10d, n = 6, F_(2,21) = 2.11, p>0.05). C Acute stress up regulates BDNF expression in BLA and this up regulation persists even after recovery (Control, n = 6; AIS+1d, n = 5; AIS+10d, n = 6, F_(2,14) = 4.82, p<0.05). BDNF expression profile was normalized to respective control levels and evaluated by Fisher's post-hoc. D Effect of acute stress and recovery from acute stress on serum corticosterone levels (Control, n = 11; AIS+1d, n = 5; AIS+10d, n = 6, Kruskal-Wallis ANOVA, χ² ₍₂₎ = 10.01, p<0.05, Mann-Whitney post-hoc, p<0.05). Significant differences *, p<0.05.