Basic Science and Pathogenesis

Lucineia Danielski, Eduarda Behenck Medeiros, Gabriel Casagrande Zabot, Adrielly Vargas, Gabriela Piovesan Fenilli, Laura Ceolin De Jesus, Gustavo De Bem Silveira, Vijayasree V. Giridharan, Tatiana Barichello, Josiane Budni

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The increasing prevalence of neurodegenerative diseases, particularly among women post-menopause, is linked to the decline in 17 β estradiol (E2). Vitamin D deficiency, common in older individuals, exacerbates this risk due to its anti-inflammatory and neuroprotective properties. Hypovitaminosis D is associated with age-related conditions, including cognitive decline. Donepezil, an acetylcholinesterase inhibitor used for Alzheimer's dementia, targets cholinergic dysfunction in normal aging and prodromal states of this disease, suggesting a potential intervention for early disease modification. METHOD: Adult female Wistar rats aged 60 or 120 days were used, submitted to ovariectomy (OVX) for 1, 4, or 8 months, supplemented with vit D, at doses of 42 and 420 IU/kg, or water or combined with DONE (1 mg/kg) orally by gavage for 21 days. The open field test (OFT) and Y-maze test were performed. RESULT: Ovariectomized rats at 60 and 120 days of age exhibit deficits in short-term spatial reference memory, as evidenced by performance in the Y-maze task. In the OFT, 60-day-old rats subjected to OVX for four months displayed impairment, a trend also observed in rats of the same age undergoing OVX for eight months, both in the control and OVX groups. Notably, 120-day-old rats subjected to OVX for 4 and 8 months failed to learn, along with their respective control groups. However, the majority of interventions successfully reversed these memory impairments, with particular efficacy observed in treatments involving vitamin D at 42 IU/kg and the combination of vitamin D with DONE. CONCLUSION: Memory impairment occurs as a result of ovariectomy (OVX). This effect persists with aging, and vit D, either alone or in combination with DONE, emerges as a significant alternative for reversing or mitigating this cognitive decline.

Original languageEnglish (US)
Pages (from-to)e091739
JournalAlzheimer's and Dementia
Volume20
DOIs
StatePublished - Dec 1 2024

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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