Time-dependent co-relation of BDNF and CREB mRNAs in adult rat brains following acute psychological stress in the communication box paradigm

Abstract

Psychological stress affects human health, and chronic stress leads to life-threatening diseases, such as depression and post-traumatic stress disorder. Psychological stress coping mechanisms involve the brain-derived neurotrophic factor (BDNF) and downstream cAMP response element binding protein (CREB), which are targets of the adverse effects of stress paradigms. Fourty-seven adult male Sprague-Dawley rats were divided into control, physical stress and six psychological stress groups which were assayed at 0h, 0.5h, 1h, 2h, 6h and 24h after communication box (CB) stress induction. Behavioral assessment using open field and elevated plus maze tests determined that CB stress significantly increased anxiety. After CB stress, the alternation of mRNA levels of BDNF and CREB were assessed at different time points by in situ hybridization. The mRNA levels of BDNF and CREB were significantly decreased, then gradually recovered over 24h to maximum levels in the hippocampus (CA1 region), prefrontal cortex (PFC), central amygdaloid nuclei (AG), shell of accumbens nucleus (NAC), periaqueductal gray (PAG) and ventral tegmental area, except for the ventral tegmental area (VTA). Moreover, mRNA levels of BDNF and CREB were positively correlated in all examined brain regions, except for the VTA region at 0 and 24h after CB stress induction. These findings suggest that BDNF and CREB may belong to the same pathway and be involved in psychological stress response mechanisms, and protect the organism from stress induced, aversive processes leading to disease.

Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas

“…Moreover, post-hoc analysis demonstrated that the change in BDNF mRNA levels in PS group was a biphasic modulation: immediately after the psychological stress, the gray intensity of BNDF ISH staining in the PS group was significantly increased and started to decline; after 2 hours, the gray intensity of the PS group became lower than that of the CON group. This result means that psychological stress in CB paradigm induced a biphasic change of BDNF mRNA: an immediate decrease followed by a gradual increase last for at least 24 hours, which is in accordance with our previous observation [ 20 ].…”

“…The gray intensity analysis confirmed our previous result [ 20 ] that the gray intensity of the BDNF ISH staining of the PS group significantly differed from that of the CON group in most of the examined brain areas (in CA1: F [2,12] = 8.907, p = 0.004; in CA3: F [2,12] = 6.291, p = 0.014; in DG: F [2,12] = 11.153, p = 0.002; in PFC: F [2,12] = 8.884, p = 0.004; in NAc: F [2,12] = 5.405, p = 0.021; in AG: F [2,12] = 8.971, p = 0.004; in PAG: F [2,12] = 5.898, p = 0.016; in DM: F [2,12] = 7.353, p = 0.008) except in VTA (F [2,12] = 1.515, p = 0.259), however, the gray intensity of FPS and CON was not differed significantly in all brain regions,as shown in Figure 2 . Moreover, post-hoc analysis demonstrated that the change in BDNF mRNA levels in PS group was a biphasic modulation: immediately after the psychological stress, the gray intensity of BNDF ISH staining in the PS group was significantly increased and started to decline; after 2 hours, the gray intensity of the PS group became lower than that of the CON group.…”

“…The current study investigated the effect of fluoxetine treatment on the expression of BDNF protein and mRNA in various brain regions in the CB stress model. Confirming with our previous results [ 20 ], the result of this study showed that the acute purely psychological stress resulted an immediate attenuation of BDNF mRNA and protein levels in most of the brain regions except VTA in the PS group in comparison with the CON group; and the BDNF expression, both in mRNA and protein, in the PS group gradually increased over 24 hours after the stress. Our result in this study also showed that the expression levels of BDNF protein and mRNA in the fluoxetine-pretreated group (FPS) were significantly higher than those in the PS group, suggesting that the fluoxetine treatment increased the expression of the BDNF protein and mRNA in various brain areas after the acute psychological stress.…”

“…These models therefore can hardly represent purely psychological stress, which are more relevant in human societies. By applying communication box (CB) paradigm, a mode of purely psychological stress without physical stimulation, we recently demonstrated that, similar with other stressors, BDNF is indeed involved in psychological stress response with a biphasic change: the levels of BDNF in most brain areas decreased immediately after the shock, but were gradually recovered at about 2 hours after the shock and then increased within at least 24 hours after the psychological stress compared with a non-stressed control group [ 20 ]. It is widely accepted that the regulation of BDNF expression in response to stress is mediated by glucocorticoid [ 13 , 21 ], but not entirely [ 7 ].…”

Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats

“…CREB signaling regulates expression of several genes, including BDNF ( 56 , 57 ). The phosphorylation of CREB subsequently results in the transcriptional regulation of c-fos, c-jun, and bcl-2 ( 58 – 60 ). CREB–BDNF signaling has been suggested to be critical in numerous neuronal biological processes, including cell survival, synaptic structure, and synaptic plasticity ( 15 , 61 ).…”