Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Abstract

In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.

Estrous cycle regulates activation of hippocampal Akt, LIM kinase, and neurotrophin receptors in C57BL/6 mice

“…Exogenous estradiol administration to ovariectomized rats increases BDNF mRNA and protein expression in the hippocampus (Gibbs, 1998, Jezierski and Sohrabji, 2001, Scharfman et al, 2003, Zhou et al, 2005. Activation of the BDNF receptor TrkB in the hippocampal formation leads to LIMK and Akt phosphorylation, dendritic spine regulation, and enhancement of long-term potentiation, similar to the effects of estradiol (Chao, 2003, Scharfman and Maclusky, 2005, Scharfman and Maclusky, 2006a, Spencer et al, 2007.…”

Correlation Between Hormonal and Neurochemical Changes and Depression With Menopausal STATUS: A Systematic Review

“…Therefore, the physiopathology of climacteric signs including depression, hot flashes etc., may correlate with the wide spectrum of sex hormones actions on neurons functions both directly through hormone receptor relations and indirectly via alterations in neurotransmitter concentration and neurotrophin activity (51). Some reports suggesting the involvement of BDNF in regulating estrogen actions showed that it could modulate the expression of BDNF via the estrogen response element on the BDNF gene (18,52). In recent years, the importance of non-hormonal alternatives for the decreasing the climacteric symptoms has enhanced, i.e.…”

Effects of multiparity on recognition memory, monoaminergic neurotransmitters, and brain-derived neurotrophic factor (BDNF)

“…Cholinergic input from the septum seems to modulate spatial memory (Smith and Pang, 2005); these same neurons transport BDNF protein from hippocampus to septum (Sobreviela et al, 1996). Furthermore, BDNF protein levels are naturally elevated during proestrus and estrus (Scharfman et al, 2003), and changes in BDNF mRNA and protein have been reported in ovariectomized rats after acute (Gibbs, 1999) and chronic (Zhou et al, 2005) estradiol treatment (for review see Scharfman and MacLusky, 2006). If multiparity exerts long-term changes on hippocampal (or septal) BDNF protein, it is possible that BDNF may underlie any positive effects of parity on spatial memory.…”