Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones

Abstract

Astroglia and steroid hormones such as estrogen and progesterone regulate cell growth, function, and protection in the central nervous system (CNS). It appears that astrocytes and steroids act in concert to promote cell survival under pathological conditions. With respect to the role of mitochondrial fusion and fission in energy metabolism, apoptosis, and proliferation, astrocyte mitochondria resemble a perfect intracellular target for steroids to modulate these processes, thereby promoting cell vitality after damage. We have studied the effects of estrogen and progesterone on cell viability in comparison with mitochondrial fusion and fission gene transcription in primary cortical astrocytes from female and male mouse brains. Estrogen-and progesterone-treated female astrocytes demonstrated an increase in cell number and proliferation marker accompanied by an upregulation of fusion and fission gene transcription, which were apparently balancing pro-and anti-apoptotic processes. On the other hand, male astrocytes exhibited no change in cell number after estrogen treatment, but a decrease after progesterone administration. This could be the consequence of stimulated apoptosis in male astrocytes by both steroids, which was counterbalanced by an increased proliferation in the presence of estrogen, whereas it was strengthened in the presence of progesterone. Supportively, estrogen promoted and progesterone decreased the transcription of fusion and fission genes. We suggest that estrogen and progesterone affect mitochondrial fusion and fission gene transcription in cortical astrocytes in a gender-specific way, thereby influencing mitochondrial function differently in both genders. Thus, interaction of sex steroids with mitochondria may represent one possible cause for gender differences in cellular pathology in the CNS.

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

“…The mRNA levels of the chemokine IFN-inducible protein 10, on the other hand, were higher in LPS-treated astrocytes derived from control or vehicle-treated females than in those obtained from males or androgenized females (202). In addition, the effects of estrogen and progesterone on the function and viability of mitochondria in astrocytes are gender dependent (12). There is evidence to support the notion that perinatal exposure to testosterone predetermines the responses of astrocytes (202).…”

Estrogen and the regulation of mitochondrial structure and function in the brain

“…Estrogen treatment prevented the OVX-induced alteration in mitochondrial dynamics [66]. In a recent study, we have investigated the effect of short-term application of 17␤-estradiol for 24 h on the expression levels of the above fusion and fission protein in cultured brain astrocytes originating from the cerebral cortex [67]. In addition, we attempted to detect differences in their regulation in male and female cells.…”

Brain region-specific vulnerability of astrocytes in response to 3-nitropropionic acid is mediated by cytochrome c oxidase isoform expression

“…Astroglial cultures were prepared from postnatal day 1 BALB/c mice as previously documented (Arnold et al 2008). Briefly, brains from decapitated mice were removed and transferred into preparation buffer consisting of 10 mM HEPES, 154 mM NaCl, 10 mM glucose, 2 mM KCl, and 15 µM bovine serum albumin.…”