Year: 2023
Type: article
Abstract: Menopause is associated with cognitive deficits and brain atrophy, but the brain region and cell-specific mechanisms are not fully understood. Here, we identify a sex hormone by age interaction whereby loss of ovarian hormones in female mice at midlife, but not young age, induced hippocampal-dependent cognitive impairment, dorsal hippocampal atrophy, and astrocyte and microglia activation with synaptic loss. Selective deletion of estrogen receptor beta (ERβ) in astrocytes, but not neurons, in gonadally intact female mice induced the same brain effects. RNA sequencing and pathway analyses of gene expression in hippocampal astrocytes from midlife female astrocyte-ERβ conditional knock out (cKO) mice revealed Gluconeogenesis I and Glycolysis I as the most differentially expressed pathways. Enolase 1 gene expression was increased in hippocampi from both astrocyte-ERβ cKO female mice at midlife and from postmenopausal women. Gain of function studies showed that ERβ ligand treatment of midlife female mice reversed dorsal hippocampal neuropathology.
Source: Nature Communications
Institution: University of California, Los Angeles
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Awards: Determining the neuroprotective role of estriol in experimental autoimmune encephalomyelitis, The Mechanism of Gray Matter Atrophy in Experimental Autoimmune Encephalomyelitis, Parental imprinting of the X chromosome: effects on neurodegeneration, G3611230001, Bringing CLARITY to EAE, G3973089391, G7665100347, Neuroprotection in MS: A Cell-Specific and Region-Specific Transcriptomics Approach, Neurodegeneration Underlying Distinct Disabilities in Multiple Sclerosis Using a Cell-Specific, Region-Specific, and Sex-Specific Approach
OpenAlex ID: W4387115400