Experimental neurology
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Experimental neurology · Jun 1998
Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function.
Recent studies suggest that women are at greater risk for Alzheimer's disease than men and that estrogen replacement can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that the increased risk for Alzheimer's-related dementia is due, in part, to the loss of ovarian function in postmenopausal women and to the effects that decreased levels of ovarian hormones have on basal forebrain cholinergic function. In the present study, the effects of aging and ovariectomy on cholinergic neurons in the rat basal forebrain were examined to determine (1) whether aging differentially affects cholinergic neurons in the basal forebrain of males vs females, and (2) whether long-term loss of ovarian function produces deficits in basal forebrain cholinergic function beyond those associated with aging and sex. ⋯ This, in turn, may increase the susceptibility of the cholinergic neurons to the effects of aging and disease and thereby contribute to basal forebrain cholinergic decline. We conclude that long-term loss of ovarian function combined with aging has a negative impact on basal forebrain cholinergic neurons. These effects may contribute to the risk and severity of cognitive decline associated with aging and Alzheimer's disease in postmenopausal women.
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Experimental neurology · Jun 1998
Plastic changes in glycine and GABA release and uptake in adult brain stem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation.
[i] In young adult guinea pigs, the effects of unilateral ossicle removal and unilateral cochlear ablation were determined on [14C]glycine or [14C]GABA release and uptake measured in subdivisions of the cochlear nucleus (CN), the superior olivary complex, and the auditory midbrain, after 2 or 5, 59, and 145 postlesion days. Activities were compared to those of age-matched, unlesioned controls. [ii] [14C]Glycine release declined bilaterally in the anteroventral and dorsal CN after ossicle removal and in the dorsal CN after cochlear ablation. [iii] Transient elevations of release occurred at 59 days in the ipsilateral posteroventral CN ([14C]glycine) and bilaterally in the ventral nucleus of the lateral lemniscus ([14C]GABA) after ossicle removal, and bilaterally in the medial superior olive ([14C]glycine) after cochlear ablation. [iv] In the medial nucleus of the trapezoid body, [14C]GABA release was depressed bilaterally 5 days after ossicle removal, but was elevated at 145 days contralaterally after ossicle removal and ipsilaterally after cochlear ablation. [v] In the contralateral central nucleus of the inferior colliculus, [14C]GABA release was elevated persistently after ossicle removal. After cochlear ablation, release was elevated at 5 days, near the control at 59 days, and elevated again at 145 days. [vi] After both lesions, [14C]glycine uptake was elevated bilaterally in the CN and medial superior olive. [14C]GABA uptake became depressed by 59 or 145 days bilaterally in the auditory midbrain. [vii] These changes may stem from regulation and may contribute to mechanisms that generate symptoms such as loudness recruitment and tinnitus, which often accompany hearing loss.