Estrogen Therapy and brain muscarinic receptor density in healthy females: A SPET study

Psychopharmacology and Emotion Research Laboratory, University of Oxford, UK.
Hormones and Behavior (Impact Factor: 4.63). 03/2007; 51(2):249-57. DOI: 10.1016/j.yhbeh.2006.10.007
Source: PubMed


Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer's disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term ET and age on brain m(1)/m(4) receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n=2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels.

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Available from: Declan Murphy, Jan 19, 2016
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    • "In human females, variations in estradiol during the natural menstrual cycle are also associated with mood changes (Derntl et al., 2008; McEwen, 2010): a negative affect is more commonly experienced when estrogen levels are declining or low; whereas a positive affect is associated with high estrogen levels, according to the significant modulatory effects of estrogen upon neurotransmitter systems involved in the regulation of affective behavior (Amin et al., 2006a,b; Norbury et al., 2007). Women with mood disorders show definite peaks that are temporally related to periods of substantial hormonal fluctuation (e.g., adolescence, the week before the onset of menses and perimenopause; Sigmon et al., 2000). "
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