Cholesterol and perhaps estradiol protect against corticosterone-induced hippocampal CA3 dendritic retraction in gonadectomized female and male rats

Abstract

Chronic stress or glucocorticoid exposure simplifies hippocampal CA3 apical dendritic arbors in male rats. In contrast to males, chronic stress either reduces CA3 basal branching or exerts no observable morphological effects in gonadally intact female rats. Under conditions that females display stress-induced CA3 dendritic retraction, such as following ovariectomy, chronic exposure to 17β-estradiol or cholesterol can negate these changes. Whether glucocorticoids produce CA3 dendritic retraction in ovariectomized females and whether neuroprotection from 17β-estradiol or cholesterol is sex-specific remains unknown. The current study examined the effects of chronic glucocorticoid exposure, in conjunction with 17β-estradiol or cholesterol administration, on hippocampal CA3 dendritic complexity. Adult male and female Sprague-Dawley rats were gonadectomized and implanted with 25% 17β-estradiol in cholesterol, 100% cholesterol, or blank Silastic capsules. Rats were then assigned to either a 21-day corticosterone (CORT) drink (400µg/mL CORT, 2.4% ethanol in tap water) or tap water (Tap, 2.4% ethanol in tap water) treatment. Brains were processed for Golgi staining, and hippocampal CA3 dendritic architecture was quantified. Results showed 21-day CORT administration reduced hippocampal CA3 apical dendritic branch points, CA3 apical dendritic length, body weight gain, and adrenal weights compared to male and female control counterparts. Furthermore, male and female rats implanted with Silastic capsules containing cholesterol or 25% 17β-estradiol in cholesterol were protected from CORT-induced CA3 apical dendritic branch reduction. No effects were observed in the CA3 basal dendritic arbors. The present results demonstrate that CORT produces hippocampal CA3 dendritic retraction in gonadectomized male and female rats and that cholesterol and 25% 17β-estradiol in cholesterol prevent this dendritic simplification.

Estradiol replacement extends the window of opportunity for hippocampal function

“…A recent report shows that serum E2 levels are higher when rats are implanted with cholesterol versus blank capsules (McLaughlin, et al, 2010), suggesting that increasing cholesterol levels may increase E2 synthesis despite OVX. This finding however was not replicated in a more recent study (Ortiz, et al, 2013) or in the current study since serum E2 levels are undetectable in all Chol-replaced animals when measured prior to surgical capsule removal.…”

Cognitive training increases dendritic arborization in the dorsal hippocampal CA1 and CA3 neurons of female and male Long–Evans rats

“…Multiple types of experimental manipulations have been used to study the strong capacity for the hippocampus to express neuronal plasticity. For example, studies have been conducted on the effects of social isolation (Silva‐Gómez, Rojas, Juárez, & Flores, ), androgens (Hajszan, Maclusky, & Leranth, ; Leranth, Hajszan, & MacLusky, ), estradiol (Gould, Woolley, Frankfurt, & McEwen, ; Murakami et al, ; Woolley & McEwen, , , ; Woolley, Weiland, McEwen, & Schwartzkroin, ), glucocorticoids (Komatsuzaki et al, ; Silva‐Gómez, Aguilar‐Salgado, Reyes‐Hernández, & Flores, ), induced stress (Lambert et al, ; McEwen & Milner, ; McLaughlin, Baran, Wright, & Conrad, ), hypobaric hypoxia (Titus et al, ), spatial learning (Moser, Trommald, & Andersen, ), ovariectomy (Ortiz et al, ; Wallace, Luine, Arellanos, & Frankfurt, ), estrous cycle (Woolley, Gould, Frankfurt, & McEwen, ), and handling and drug injection procedures (Horner, O'Regan, & Arbuthnott, ) on the neuronal morphology of the CA1 region of the hippocampus. The CA3 region has also received attention in terms of its capacities for dendritic remodeling as a result of the effects of stress (McLaughlin et al, ; Watanabe, Gould, & McEwen, ).…”

Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum

“…Brains and adrenal glands were then extracted. All brains were stained with FD Rapid Golgistain™ Kits (FD NeuroTechnologies, Baltimore MD) according to the manufacturer's instructions and previous publications (Hoffman et al, 2011, Ortiz et al, 2013). Briefly, freshly extracted brains were rapidly rinsed with distilled water and then placed in an impregnation solution.…”