ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
The transcription factor cAMP response element-binding protein (CREB) plays a critical role in plasticity processes underlying learning and memory. We investigated the phosphorylation of CREB in rat brain after forced swimming, a stressor known to impact on higher limbic and neocortical brain areas. As shown by immunohistochemistry, forced swimming increased phosphorylated CREB (P-CREB) levels in the dentate gyrus, all neocortical areas, the medial, lateral and basolateral nuclei of the amygdala, cerebellum but not in the hypothalamic paraventricular nucleus. Distinct differences in the P-CREB pattern were observed in the deeper vs. superficial layers of the neocortex. The response in P-CREB was stressor type-specific because exposure to either ether or a cold environment was ineffective. The forced swimming-induced changes in P-CREB levels showed a biphasic time-course: an early peak detected at 15 min was followed by a marked drop at 60 min; a second rise starting after 1–2 h, reached maximal values between 6 and 8 h, and remained elevated for at least 48 h. Examination of the neuroanatomical induction pattern of the CRE-inducible immediate early gene product c-fos revealed that it was only partly overlapping with that of P-CREB. Western analyses showed that only the 43-kDa CREB protein (an enhancer of CRE-containing promotors) was phosphorylated after forced swimming, while other members of the CREB/ATF family (CREM, ATF-1 and ATF-2) remained unaffected. The NF-κB pathway was not activated, indicating that forced swimming does not unspecifically evoke transcription factor activation. Thus, in contrast to physical stressors, such as ether or cold exposure, forced swimming, a stressor with a strong psychological component, elicits the recruitment of the CREB pathway in a widespread manner in the limbic system and neocortex; brain regions known to be implicated in various forms of (stress-related) learning and memory.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1460-9568.2002.01934.x
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