Ovariectomy reduces cholinergic modulation of excitatory synaptic transmission in the rat entorhinal cortex

Estrogens are thought to contribute to cognitive function in part by promoting the function of basal forebrain cholinergic neurons that project to the hippocampus and cortical regions including the entorhinal cortex. Reductions in estrogens may alter cognition by reducing the function of cholinergic inputs to both the hippocampus and entorhinal cortex. In the present study, we assessed the effects of ovariectomy on proteins associated with cholinergic synapses in the entorhinal cortex. Ovariectomy was conducted at PD63, and tissue was obtained on PD84 to 89 to quantify changes in the degradative enzyme acetylcholinesterase, the vesicular acetylcholine transporter, and muscarinic M-1 receptor protein. Although the vesicular acetylcholine transporter was unaffected, ovariectomy reduced both acetylcholinesterase and M-1 receptor protein, and these reductions were prevented by chronic replacement of 17 beta-estradiol following ovariectomy. We also assessed the effects of ovariectomy on the cholinergic modulation of excitatory transmission, by comparing the effects of the acetylcholinesterase inhibitor eserine on evoked excitatory synaptic field potentials in brain slices obtained from intact rats, and from ovariectomized rats with or without 17 beta-estradiol replacement. Eserine is known to prolong the effects of endogenously released acetylcholine, resulting in an M-1-like mediated reduction of glutamate release at excitatory synapses. The reduction in excitatory synaptic potentials in layer II of the entorhinal cortex induced by 15-min application of 10 mu M eserine was greatly reduced in slices from ovariectomized rats as compared to intact rats and ovariectomized rats with replacement of 17 beta-estradiol. The reduced modulatory effect of eserine is consistent with the observed changes in cholinergic proteins, and suggests that reductions in 17 beta-estradiol following ovariectomy lead to impaired cholinergic function within the entorhinal cortex.

Automated summary

Estrogens play a role in promoting the function of cholinergic neurons and have an impact on cognitive function. This study found that ovariectomy reduces the expression of cholinergic synaptic proteins in the entorhinal cortex, and this reduction can be prevented by estradiol replacement. Ovariectomy also impairs the cholinergic modulation of excitatory transmission in the entorhinal cortex, which may be related to the changes in cholinergic proteins.