450 International Medical Journal Vol. 26, No. 6, pp. 450 -452, December 2019 PSYCHOLOGICAL MEDICINE Menopause Rodent Models: Suitability for Cognitive Aging Research Rahimah Zakaria”, Badriya A1 Rahbi2’, Asma Hayati Ahmad* 12 3 4 * ’, Rozzana Mohd Said3’, Zahiruddin Othman4’, Khairunnuur Fairuz Azman", Che Badariah Abdul Aziz1’ ABSTRACT Background: Recently published findings noted that women suffer from Alzheimer disease, a form of neurodegenerative dis order, more often than men, even accounting for the fact that women on average live longer. Objective: Menopause rodent model may be an invaluable tool for assessing longitudinal effects of hormones and aging, as well as providing access to body tissues especially brain, from which insight into the mechanisms related to cognitive aging and Alzheimer disease can be gleaned. Method: This review highlights the suitability and limitations of using menopause rodent models for cognitive aging research. Conclusion: Intact aging and OVX animals mimic natural and surgical menopause, respectively, hence making them suitable menopause models for cognitive aging research after taking into account their limitations. KEY WORDS Alzheimer disease, menopause, rodents, intact aging, ovariectomized, accelerated ovarian failure INTRODUCTION Menopause is the cessation of menstruation at the end of a woman's reproductive life and, by definition, is the absence of menstruation for a year". Natural menopause is the result of loss of ovarian follicular activ ity due to natural aging23’. Another form of menopause is medically-in duced menopause. It is the loss of ovarian follicular activity due to sur gery, chemotherapy or radiation. The term perimenopause is defined by the World Health Organization and the North American Menopause Society as two to eight years preceding menopause and one year following final men ses43’1 . Menopausal transition stage is divided into early and late phases. It is characterised by irregularity in menstrual cycle with a discrepancy of 7 days or more from the normal cycle. For late menopausal transition, there are 2 or more skipped cycles with an interval of amenorrhea of equal to or more than 60 days71 . Postmenopausal stage is also divided into two phases, early and late postmenopause. Early postmenopause occurs within 5 - 8 years after cessation of the last menstrual period, while late postmenopause begins after early postmenopause until the remaining of the life span71 . MENOPAUSE ANIMAL MODELS Menopause has been known to cause brain-related symptoms such as depression, anxiety81 , insomnia91 and cognitive deficits101 . Non-human primates experience human-like menopause, but menopause studies in such long-lived mammals are unfeasible'" because of cost and complex variables in lifestyle, history, and time required to study aging systems. Therefore, this review focuses on alternative menopause models using small laboratory animals such as rodents for cognitive aging research. Genetically modified animal models (transgenic and knock-out animals) such as aromatase deficiency and APP23 transgene mouse model121 , and Follicle Stimulating Hormone receptor knockout (FORKO) mice13’, however, are beyond the scope of this review. The ideal menopause model should have similarity to endocrine and neuroendocrine aspects of human ovarian biology, and if possible, the model should have reproductive traits that can be manipulated in the laboratory, that is, by transgenic or natural mutations that result in an accelerated or delayed example of ovarian aging. Rodents have a maxi mum lifespan of 5 years, their ovaries deteriorate as they age and they can be genetically manipulated, making them a suitable menopause m odel141 . Table 1 summarizes comparison between human and rodent reproductive senescence. Received on December 11, 2018 and accepted on June 20, 2019 1) Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Malaysia 2) College of Health Science, Ministry of Health Muscat, Oman 3) Faculty of Health Science, Universiti Teknologi MARA Puncak Alam Campus 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia 4) Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Malaysia Correspondence to: Zahiruddin Othman (e-mail: zahirkb@usm.my) (E) 2019 Japan Health Sciences University & Japan International Cultural Exchange Foundation