Liraglutide mends cognitive impairment by averting Notch signaling pathway overexpression in a rat model of polycystic ovary syndrome.

AIMS: Polycystic ovary syndrome (PCOS), the rifest endocrine disorder in women, is involved in disrupting many metabolic processes. However, the impact of PCOS on cognitive deficits is still uncertain. Recently, Notch signaling pathway was identified as a key modifier in regulating the pathological process in the ovary and various neurodegenerative disorders. Liraglutide has favourable neuroprotective effects that may protect against the possible cognitive dysfunction in PCOS.

MAIN

METHODS

PCOS was induced in rats by administrating Letrozole orally for 21 successive days. Then, Liraglutide (LIR) was administered intraperitoneally for 30 days. Memory was examined using Y-maze, novel object recognition (NOR), and Morris water maze (MWM) tests. Western blotting, enzyme immunoassay, and quantitative real-time PCR were used to examine Notch signaling downstream targets, as well as assessing the expression of the components of various pathways cross talked with Notch signaling in memory impairment. Furthermore, histopathological examination was performed to examine neuronal changes.

KEY FINDINGS: Notch signaling was overexpressed in PCOS rats, which increased Aβ aggregation, apoptosis, and neuroinflammation. Additionally, histopathological examination showed neuronal degeneration, which was marked by diminished acetylcholine levels in the PCOS rats' hippocampi. Finally, serum levels of insulin and testosterone were elevated while estradiol was reduced. Treatment with LIR repaired Notch signaling-attributed changes and improved the PCOS-induced memory impairment in rats.

SIGNIFICANCE: The obtained findings confirm that Notch signaling activation in the hippocampus of rats impairs cognitive functions in PCOS, which is mitigated by LIR. Therefore, LIR may offer a novel therapeutic intervention to impede PCOS-induced dementia.