Defective Hippocampus-Dependent Spatial Memory in Mouse Model of Polyendocrine metabolic ovarian syndrome (PMOS, formerly PCOS).

Abstract

Polyendocrine metabolic ovarian syndrome (PMOS), formerly called as Polycystic Ovarian Syndrome (PCOS), is a complex endocrine disorder characterised by hyperandrogenism, oligo-or anovulation, and polycystic ovaries. Endocrine dysfunction in PMOS disrupts both hormonal and neurotransmitter balance, contributing to the psychological distress frequently reported by affected individuals. Although hormonal imbalances have been associated with memory impairments, their specific contribution to cognitive dysfunction in PMOS remains incompletely understood. In this study, we investigated the impact of PMOS on the hippocampus, a brain region critical for memory formation and highly sensitive to sex steroid modulation. A dehydroepiandrosterone (DHEA)-induced PMOS mouse model was employed to assess anxiety-like behaviour, locomotion, and memory. In the open field test (OFT), DHEA-treated mice spent significantly less time in the central zones and travelled a shorter total distance compared with controls, indicating increased anxiety-like behaviour. DHEA treatment also resulted in significantly impaired performance in both the object location test (OLT) and novel object recognition test (NORT), as reflected by a reduced discrimination index. Analysis of hippocampal immediate early gene expression using qRT-PCR revealed altered transcription of memory-related markers, including downregulation of Npas4 and Grin2a, and upregulation of Grin1, Arc, Egr1, and Egr2. Collectively, these findings suggest that elevated androgen levels induce anxiety- and depression-like behaviours and impair cognitive function, including spatial, recognition, and motor learning abilities, in PMOS. Our results further indicate that disrupted cortex-hippocampus communication may underlie these cognitive deficits, underscoring the importance of evaluating memory and cognitive health in women with PMOS to support brain health and overall well-being. Graphical summaryCartoon representation of the impact of hyperandrogenism on anxiety, spatial memory, and cognition in PMOS pathology. O_FIG O_LINKSMALLFIG WIDTH=132 HEIGHT=200 SRC="FIGDIR/small/721991v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1d0125eorg.highwire.dtl.DTLVardef@1660d8aorg.highwire.dtl.DTLVardef@102ff8aorg.highwire.dtl.DTLVardef@1d6e06b_HPS_FORMAT_FIGEXP M_FIG C_FIG