Anatomical evidence for transsynaptic influences of estrogen on brain-derived neurotrophic factor expression.
Several studies have demonstrated that estrogen modulates brain-derived neurotrophic factor (BDNF) mRNA and protein within the adult hippocampus and cortex. However, mechanisms underlying this regulation are unknown. Although an estrogen response element (ERE)-like sequence has been identified within the BDNF gene, such a classical mechanism of estrogen-induced transcriptional activation requires the colocalized expression of estrogen receptors within cells that produce BDNF. Developmental studies have demonstrated such a relationship, but to date no studies have examined colocalization of estrogen receptors and BDNF within the adult brain. By utilizing double-label immunohistochemistry for BDNF, estrogen receptor-alpha (ER-alpha), and estrogen receptor-beta (ER-beta), we found only sparse colocalization between ER-alpha and BDNF in the hypothalamus, amygdala, prelimbic cortex, and ventral hippocampus. Furthermore, ER-beta and BDNF do not colocalize in any brain region. Given the recent finding that cortical ER-beta is almost exclusively localized to parvalbumin-immunoreactive GABAergic neurons, we performed BDNF/parvalbumin double labeling and discovered that axons from cortical ER-beta-expressing inhibitory neurons terminate on BDNF-immunoreactive pyramidal cells. Collectively, these findings support a potential transsynaptic relationship between estrogen state and cortical BDNF: By directly modulating GABAergic interneurons, estrogen may indirectly influence the activity and expression of BDNF-producing cortical neurons.
Blurton-Jones
M
M
Department of Neurosciences, University of California-San Diego, La Jolla, California 92093-0626, USA.
Kuan
P N
PN
Tuszynski
M H
MH
D000679:Amygdala / Q000737:chemistry; D000818:Animals; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis* / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000737:chemistry; D007031:Hypothalamus / Q000737:chemistry; D007150:Immunohistochemistry; D007395:Interneurons / Q000737:chemistry* / Q000378:metabolism; D019579:Neocortex / Q000737:chemistry* / Q000378:metabolism; D010320:Parvalbumins / Q000032:analysis; D017966:Pyramidal Cells / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid
D019208:Brain-Derived Neurotrophic Factor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D010320:Parvalbumins; D011960:Receptors, Estrogen; D005680:gamma-Aminobutyric Acid