TY - JOUR
T1 - Longitudinal Effects of Immediate and Delayed Estradiol on Cognitive Performance in a Spatial Maze and Hippocampal Volume in Menopausal Macaques Under an Obesogenic Diet
AU - Zimmerman, Benjamin
AU - Kundu, Payel
AU - Liu, Zheng
AU - Urbanski, Henryk F.
AU - Kroenke, Christopher D.
AU - Kohama, Steven
AU - Bethea, Cynthia
AU - Raber, Jacob
N1 - Funding Information:
The authors would like to thank Kevin Mueller, Lynn Bajorek, Grace Mammarella, and Bess Glickman for their contributions to the training of the monkeys and especially to Kevin Mueller for his assistance in preparing data for analysis. Funding. Funding for this study was provided by the National Institutes of Health through grant R24OD11895 to CB, RF1AG062220 to HU, and grant P51 OD11092 to the Oregon National Primate Research Center. Additionally, support for PK was provided by a grant from the National Institute of Environmental Health Sciences (NIEHS), T32ES007060. Support for BZ was provided by a Beckman Postdoctoral Fellowship and a Burroughs Wellcome Fund Collaborative Research Travel Grant (1018797). Partial support for JR was provided by RF1 AG059088 and R21 AG065914.
Publisher Copyright:
© Copyright © 2020 Zimmerman, Kundu, Liu, Urbanski, Kroenke, Kohama, Bethea and Raber.
PY - 2020/6/24
Y1 - 2020/6/24
N2 - The consumption of a diet high in fat and refined sugars has several health risks, including the development of cognitive decline and neurodegeneration. For women, menopause carries additional health risks that may interact with a high-fat diet in negative ways. Some symptoms of menopause, including cognitive impairments, can be modulated by hormone replacement therapy (HRT), but the hormonal formulation and the timing of the treatment relative to the onset of menopause are critical factors determining its efficacy. Little is known about how obesogenic, high-fat, high-sugar diets interact with HRT in menopause to affect cognition and neurodegeneration. Given the high prevalence of the consumption of an obesogenic Western-style diet, understanding how the effects of HRT are modulated by an obesogenic diet is critical for developing optimized therapeutic strategies for peri- and post-menopausal women. In this study, we investigated by magnetic resonance imaging (MRI) the effects of either immediate or delayed estradiol hormone therapy on cognition and neuroanatomy following ovo-hysterectomy (OvH) of aged, female rhesus macaques on an obesogenic diet. The macaques were followed for 2.5 years after ovo-hysterectomy, with four time points at which anatomical MRIs were acquired. Analysis of hippocampal volumes revealed an interaction between time point and treatment; hippocampal volumes in the delayed estrogen group, but not the immediate estrogen group, increased over time compared to those in untreated controls. Performance on a hippocampal-dependent spatial maze task showed improved performance in estrogen treated animals compared to OvH macaques given placebo. These results indicate that HRT may contribute to beneficial cognitive outcomes after menopause under an obesogenic diet.
AB - The consumption of a diet high in fat and refined sugars has several health risks, including the development of cognitive decline and neurodegeneration. For women, menopause carries additional health risks that may interact with a high-fat diet in negative ways. Some symptoms of menopause, including cognitive impairments, can be modulated by hormone replacement therapy (HRT), but the hormonal formulation and the timing of the treatment relative to the onset of menopause are critical factors determining its efficacy. Little is known about how obesogenic, high-fat, high-sugar diets interact with HRT in menopause to affect cognition and neurodegeneration. Given the high prevalence of the consumption of an obesogenic Western-style diet, understanding how the effects of HRT are modulated by an obesogenic diet is critical for developing optimized therapeutic strategies for peri- and post-menopausal women. In this study, we investigated by magnetic resonance imaging (MRI) the effects of either immediate or delayed estradiol hormone therapy on cognition and neuroanatomy following ovo-hysterectomy (OvH) of aged, female rhesus macaques on an obesogenic diet. The macaques were followed for 2.5 years after ovo-hysterectomy, with four time points at which anatomical MRIs were acquired. Analysis of hippocampal volumes revealed an interaction between time point and treatment; hippocampal volumes in the delayed estrogen group, but not the immediate estrogen group, increased over time compared to those in untreated controls. Performance on a hippocampal-dependent spatial maze task showed improved performance in estrogen treated animals compared to OvH macaques given placebo. These results indicate that HRT may contribute to beneficial cognitive outcomes after menopause under an obesogenic diet.
KW - aging
KW - hormone replacement therapy
KW - menopause
KW - neurodegeneration
KW - obesogenic diet
UR - http://www.scopus.com/inward/record.url?scp=85087713849&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087713849&partnerID=8YFLogxK
U2 - 10.3389/fneur.2020.00539
DO - 10.3389/fneur.2020.00539
M3 - Article
AN - SCOPUS:85087713849
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
SN - 1664-2295
M1 - 539
ER -