THE EFFECTS OF TWO YEARS ESTROGEN LOSS AND REPLACEMENT ON CHOLINERGIC NEURONS AND CORTICAL CHOLINERGIC FIBERS IN MONKEYS
G.P. Tinkler*, J.R. Tobin, and M.L. Voytko
Interdisciplinary Neuroscience Program,
Wake Forest University School of Medicine,
Medical Center Boulevard,
Winston-Salem, NC 27157
Women can expect to spend one-third of their lives postmenopause, yet
the neurobiological consequences of chronic estrogen loss and
replacement are poorly understood. Additionally, only a handful of
studies investigating this issue have been conducted in humans or
non-human primates. The basal forebrain cholinergic system (BFCS)
contains estrogen receptors and is sensitive to changes in estrogen
state in rodents. We have found that normal performance on a
visuospatial attention task is dependent upon the BFCS or estrogen.
The current study investigated the effects of two years estrogen loss
and replacement on neurons in the nucleus basalis and their cortical
cholinergic projections in surgically menopausal adult monkeys. Using
stereological methods we analyzed the number and volume of the
cholinergic neurons of the nucleus basalis, and also analyzed
cholinergic fiber length and density in cortical regions that are part
of a frontoparietal visuospatial attention network, in intact monkeys
(n=6) and ovariectomized monkeys treated with placebo (n=6) or estrogen
(n=6) for two years. We did not find changes in the number or size of
nucleus basalis cholinergic neurons, or of cholinergic fiber length or
density in parietal cortex (area 7a) or ventrolateral principal sulcus
(area 46v), following 2 years of estrogen loss or replacement. In
contrast, we did find a layer-specific decrease in cholinergic fiber
length and density in the dorsal bank of the principal sulcus (area
46d) following two years of estrogen loss. Daily oral treatment with
estrogen prevented this decrease. The results suggest that long-term
estrogen loss may have subtle but significant neurobiological
consequences in the primate cholinergic system that may be prevented
with long-term estrogen replacement.
Supported by: NIA AG13204 and a grant from the Wake Forest University School of Medicine Women’s Health Center of Excellence.
Key words:
menopause acetylcholine stereology macaque basalis
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