Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation.
The present studies compared the regulation of the neurotrophin ligands and receptors by estrogen in young adult and reproductively senescent rats. Both groups of animals were ovariectomized and replaced with 17beta-estradiol or placebo pellets for 4 weeks. Protein expression of specific neurotrophins and their receptors were measured in the olfactory bulb and its basal forebrain afferent, the horizontal limb of the diagonal band of Broca (hlDBB). Young-adult rats responded to estrogen with an increase in the expression of brain-derived neurotrophic factor (BDNF) in the olfactory bulb and hlDBB, as well as bulbar trkA and trkB receptors. Older rats did not respond to estrogen in this manner. Additionally, estrogen treatment decreased the expression of the universal neurotrophin receptor p75 in young adult animals, but increased expression of this receptor in reproductively senescent rats. The latter group, however, had significantly greater estrogen receptor alpha (ERalpha) expression in the olfactory bulb as compared to their younger counterparts, but very low expression of the steroid receptor coactivator, SRC-1. Changes in the proportion or ratio of steroid receptor/coactivator systems in the aging forebrain may contribute to the refractory response to estrogen in the reproductively senescent animals.
Jezierski
M K
MK
Department of Human Anatomy and Medical Neurobiology, The Texas A&M University System Health Science Center, 228 Reynolds Medical Building, College Station, TX 77843-1114, USA.
Sohrabji
F
F
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005260:Female; D051548:Histone Acetyltransferases; D020932:Nerve Growth Factor / Q000032:analysis / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D056920:Nuclear Receptor Coactivator 1; D009830:Olfactory Bulb / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000032:analysis / Q000378:metabolism; D020917:Receptor, trkA / Q000032:analysis / Q000378:metabolism; D020813:Receptor, trkB / Q000032:analysis / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism; D012686:Septal Nuclei / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D047628:Estrogen Receptor alpha; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D011960:Receptors, Estrogen; D014157:Transcription Factors; D004958:Estradiol; D020932:Nerve Growth Factor; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D020917:Receptor, trkA; D020813:Receptor, trkB; C073922:neurotrophin 4