Ovary-Dependent Degeneration in the Hypothalamic Arcuate Nucleus*

Abstract

The effects of estradiol valerate and constant light exposure on the histological appearance of the arcuate nucleus were assessed in female rats. Both of these treatments caused significant increases in the numbers of reactive microglial cells and astrocytic granules in the nucleus. Ovariectomy before either treatment prevented the glial reaction, indicating that the experimental manipulations triggered the secretion of an ovarian product which appears to be selectively toxic to the arcuate nucleus. The fact that monthly injections of estradiol valerate in male rats produced the same profile of degeneration in the arcuate nucleus suggests that the neuropathological agent may itself be estradiol. Ovariectomy also significantly reduced arcuate microglial reactivity associated with normal aging, which suggests that cyclic surges of endogenous estradiol may be capable of gradually producing an arcuate lesion. This phenomenon may accout for the hypothalamic reproductive failure associated with normal aging in the rat.

Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells

“…Recently it has also been shown that EV-induced PE results in a selective loss of~-endorphin containing neurons with the arcuate nucleus of the hypothalamus (Desjardins et al, 1993). Brawer et al (1980) have demonstrated that ovariectomy prior to EV treatment or continuous illumination prevented the development of hypothalamic pathology in adult female rats, suggesting that an ovarian product is required for the condition to occur. Conversely, chronic exposure to high-physiological concentrations of unconjugated estradiol in gonadectomized male and female rats results in similar senescence-like pathological changes within the arcuate nucleus (Schipper et al, 1982;Brawer et al, 1983).…”

“…• (Srebro, 1971) and chronic estrogenization (Brawer et al, 1980;Brawer et al, 1983) induce the accumulation of these astrocytic inclusions. As discussed below, this estrogenic effect on Gomori-positive hypothalamic astrocytes may play a critical role in the development of reproductive failure in rodents .…”

“…However, in female rats the decline in the reproduct;ve system seems to be due to a decrease in the ability of the hypothalamus to release gonadotrophin releasing hormone (Meites et al, 1987;Finch, 1978). The onset of PE can occur as a consequence of natural aging (Ascheim, 1976;Schipper et al, 1981) or as a result of external influences such as exposure to continuous illumination or a single intramuscular dose of 2 mg estradiol valerate (EV; Brawer et al, 1978;Brawer et al, 1980). Administration of EV to young adult female rats results in axodendritic damage in the arcuate nucleus of the hypothalamus associated with the formation of myelin figures, synaptic loss and remodelling, increased numbers of reactive microglial cells containing phagocytosed material, and an accumulation of astrocytes…”

Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study

“…In rodent hypothalamus, the astrocytic inclusions accumulate with aging (Schipper et al, 1981) and chronic estrogen exposure (Brawer et al, 1980(Brawer et al, , 1983. In the hypothalamic arcuate nucleus, chronic estrogenization induces dendritic damage and synaptic remodeling in close proximity to heavily granulated Gomori astrocytes (Brawer et al, 1978;Naftolin et al, 1988;Olmos et al, 1989).…”

Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice

“…The enhancement of the bfl-1 response by estrogen treatment suggests another potential neuroprotective mechanism for this steroid hormone. Microglia express the ER-β estrogen receptor (48), and microglia in the hypothalamus are activated during the estrous cycle or in response to a single estradiol injection (49). Equally, the failure of an early microglial response in the diabetic brain may contribute to increased infarction.…”