Effects of Exercise Training during Advanced Maternal Age on the Cognitive Function of Offspring

Abstract

Advanced maternal age (AMA) denotes an age of ≥35 years during the time of delivery. Maternal metabolism affects the offspring's physical and neurological development as well as their cognitive function. This study aimed to elucidate the effects of exercise training among old female animals on the cognitive function, hippocampal neuroplasticity, mitochondrial function, and apoptosis in the offspring. We found that the offspring of mothers with AMA without exercise training had decreased spatial learning and memory, brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95) protein levels, neurogenesis, and mitochondrial function, as well as hippocampal cell death. Contrastingly, offspring of mothers with AMA with exercise training showed improved spatial learning, memory, hippocampal neuroplasticity, and mitochondrial function. These findings indicate that despite the AMA, increasing fitness through exercise significantly contributes to a positive prenatal environment for fetuses. The maternal exercises augmented the hippocampal levels of BDNF, which prevents decreased cognitive function in the offspring of mothers with AMA.

Keywords: advanced maternal age; cognitive function; exercise; hippocampus; mitochondria; neuroplasticity; offspring.

Figure 1

Effects of maternal exercise on spatial learning (A) and memory (B) in the offspring from mothers with advanced maternal age (AMA). The Morris water maze task was used to evaluate spatial learning and memory. CON: offspring from the control group; CON + EX: offspring from the control and exercised group; AMA: offspring from the advanced maternal age group; AMA + EX: offspring from the advanced maternal age and exercised group. Data are expressed as means ± standard error of the mean (SEM). * p < 0.05 compared to the CON group. # p < 0.05 compared to the AMA group.

Figure 2

Effects of exercise on BDNF and PSD95 in the hippocampus of the offspring from mothers with advanced maternal age (AMA). CON: offspring from the control group; CON + EX: offspring from the control and exercised group; AMA: offspring from the advanced maternal age group; AMA + EX: offspring from the advanced maternal age and exercised group. Data are expressed as means ± standard error of the mean (SEM). * p < 0.05 compared to the CON group. # p < 0.05 compared to the AMA group.

Figure 3

Effects of maternal exercise on mitochondrial Ca²⁺ retention (A) and H₂O₂ emission (B) in the hippocampus of offspring from mothers with advanced maternal age (AMA). CON: offspring from the control group; CON + EX: offspring from the control and exercised group; AMA: offspring from the advanced maternal age group; AMA + EX: offspring from the advanced maternal age and exercised group; GM: glutamate + malate; GMS: GM + succinate; GMSG3P: GMS + glycerol-3-phosphate. Data are expressed as means ± standard error of the mean (SEM). * p < 0.05 compared to the CON group. # p < 0.05 compared to the AMA group.

Figure 4

Effects of exercise on apoptosis (A) and cell death (B) in the hippocampus and dentate gyrus of offspring from mothers with advanced maternal age (AMA). Representative photomicrographs and data for TUNEL-positive cells are shown. The scale bar represents 50 µm. CON: offspring from the control group; CON + EX: offspring from the control and exercised group; AMA: offspring from the advanced maternal age group; AMA + EX: offspring from the advanced maternal age and exercised group. Data are expressed as means ± standard error of the mean (SEM). * p < 0.05 compared to the CON group. # p < 0.05 compared to the AMA group.

Figure 5

Effects of exercise on cell differentiation and neurogenesis in the hippocampal dentate gyrus of the offspring from mothers with advanced maternal age (AMA). Representative photomicrographs and data for DCX- and NeuN/BrdU-positive cells are shown. The scale bar represents 50 µm. CON: offspring from the control group; CON + EX: offspring from the control and exercised group; AMA: offspring from the advanced maternal age group; AMA + EX: offspring from the advanced maternal age and exercised group; NeuN: neuronal nuclear protein; BrdU: 5-bromo-2’-deoxyuridine. Data are expressed as means ± standard error of the mean (SEM). * p < 0.05 compared to the CON group. # p < 0.05 compared to the AMA group.