title: Effects of estrogen and fimbria/fornix transection on p75NGFR and ChAT expression in the medial septum and diagonal band of Broca.
abstract: NGF receptor-expressing cells located in the basal forebrain have recently been shown to contain estrogen (E) receptors (Toran-Allerand and MacLusky. 1989. Soc. Neurosci. Abstr. 15: 954). In the present study, we have examined the effects of E-treatment on p75NGFR and choline acetyltransferase (ChAT) expression by neurons in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca using immunocytochemical and in situ hybridization techniques. First, since E-treatment has been shown to affect neuronal survival and to stimulate synaptic reorganization and growth within various regions of the brain, we hypothesized that E-treatment might attenuate the loss of p75NGFR immunoreactivity (IR) which occurs in the MS and VDB following transection of the fimbria/fornix. Contrary to our hypothesis, E-treatment did not attenuate the effects of fimbria/fornix transection. In fact, E-treatment alone produced a significant decrease in the number of p75NGFR-IR cells detected in the MS. Subsequent experiments confirmed that chronic E-treatment produces a down-regulation of both p75NGFR-IR and p75NGFR mRNA in the MS and VDB. In the MS, estrogen appeared to affect a subpopulation of p75NGFR-expressing neurons which were also affected by fimbria/fornix transection since the effects of these two treatments were not additive. In addition, effects of E-treatment on p75NGFR-IR were sex-specific (observed in females but not in males) and were reversible in the MS after 2 weeks, but not after 4 weeks (allowing 2 weeks recovery), of E-treatment. A time-course analysis revealed that effects of E-treatment on p75NGFR-IR were not observed until after 16 days (MS) or 30 days (VDB) of E-treatment and were preceded by a significant and transient increase in ChAT expression in both the MS and VDB. The data are consistent with the possibility that continuous, long-term exposure to gonadal steroids may contribute to a loss of p75NGFR-expressing neurons with age. In addition, the data suggest that p75NGFR expression may play a role in regulating the functioning of specific basal forebrain cholinergic neurons. Different mechanisms by which E-treatment might influence ChAT and p75NGFR expression in brain are discussed.
authors.affiliation: Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, New York 10021.
authors.forename: R B
authors.initials: RB
authors.lastname: Gibbs
authors.forename: D W
authors.initials: DW
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity; D010052:Ovariectomy; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D013997:Time Factors
chemical_list: D004343:Drug Implants; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D004958:Estradiol; D002795:Choline O-Acetyltransferase