Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing.
Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss.
School of Biomedical Sciences, Kent State University, Kent, OH, United States; Department of Biological Sciences, Kent State University, Kent, OH, United States.
Jeffrey A
JA
Blair
College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States.
Russell
R
Palm
Department of Neurosciences, Case Western Reserve University, Cleveland, OH, United States.
Jaewon
J
Chang
Department of Biological Sciences, Kent State University, Kent, OH, United States.
Henry
H
McGee
Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Xiongwei
X
Zhu
Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Xinglong
X
Wang
Department of Biological Sciences, Kent State University, Kent, OH, United States. Electronic address: gcasades@kent.edu.
Gemma
G
Casadesus
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood*; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control; D010052:Ovariectomy / Q000009:adverse effects* / Q000523:psychology; D012098:Reproduction / Q000187:drug effects; D013131:Spine / Q000187:drug effects; D013997:Time Factors
D004967:Estrogens; D004958:Estradiol; D007986:Luteinizing Hormone
Aging; Cognition; Estrogen; Luteinizing hormone; Menopause; Ovariectomy; Spine density; Timing