Effect of Oestradiol on Neurotrophin receptor expression in Cholinergi neurons in Vivo (#257)
Neurotrophin receptors (NRs) such as TrkA, TrkB and p75 show high expression on basal forebrain cholinergic neurons (BFCN) and have been implicated in the promotion of plasticity, neurogenesis and neuronal survival. Previous studies have suggested that estradiol (E2) may play a significant role in the regulation of neurotrophin action. In the current study, we investigated the effect of E2 deficiency on the expression of NRs on BFCN. We also observed if oestrogen receptor α (ERα) and the NRs were co-localised on the same BFCNs using multiple immunolabelling. To eliminate circulating E2 levels, 6-8 week old female C57BL6 mice underwent bilateral ovariectomy (OVX) or sham surgery, a third group of mice after bilateral OVX were implanted with a subcutaneous E2 capsule. We found that the number of TrkA receptor (TrkAR) expressing choline acetyltransferase (ChAT) positive neurons was significantly reduced in the medial septum (MS) in the absence of E2 two weeks post-OVX. A significant reduction in TrkBR expressing ChAT positive cells was also observed in OVX mice in the MS and nucleus basalis magnocellularis (NBM) but to a lesser extent. p75R expression was found to be reduced in the NBM and striatum but not in the MS. NR levels in mice with E2 replacement were not significantly different from sham operated mice. We also showed that ERα was present on a small percentage of TrkAR and TrkBR positive neurons in the MS and NBM and on a high percentage of TrkAR positive neurons in the striatum, similarly ERα was seen on low levels on p75 neurons in the MS and NBM but not on striatal neurons. These results indicate that E2 influences NR expression on BFCNs, with effects depending on NR type and neuroanatomical location and may be related to the expression of ERα on these neurons.