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Motherhood and ovarian hormones influence hippocampus-dependent cognition and neurogenesis later in life Roes, Meighen Maria

Abstract

Age-related cognitive decline in women may be influenced by hormonal experiences over the lifespan including parity (pregnancy and motherhood) and menopause. Previous research implicates hippocampal neurogenesis in spatial learning and age-related cognitive decline and indicates that different regions of the hippocampus (dorsal and ventral) may contribute differentially to spatial working and reference memory. Therefore, the current study investigates influences of parity and ovarian hormones on hippocampus-dependent spatial working and reference memory and neurogenesis during middle age. Multiparous and nulliparous middle-aged rats were either ovariectomized or received sham surgery and were injected with the DNA synthesis marker bromodeoxyuridine (BrdU). Rats were trained on working/reference (hidden platform moved every two days) and reference (hidden platform was stationary) memory versions of the Morris water maze on days 12-21 after BrdU injection. On day 22 rats were given a probe trial to assess memory retention. Multiparous rats had enhanced early working/reference memory acquisition compared to nulliparous rats and this was more prominent in ovariectomized rats. In contrast, nulliparous females had better reference memory acquisition compared to multiparous rats and had enhanced spatial reference memory during the probe trial. Multiparous females had a larger ventral dentate gyrus and greater density of immature neurons compared to nulliparous females, whereas nulliparous females had greater density of older BrdU-labelled cells in the dentate gyrus compared to multiparous females. Depending on ovarian hormone status and parity, neurogenesis in the dorsal dentate gyrus correlated with measures of spatial reference learning, whereas neurogenesis in the ventral dentate gyrus correlated with spatial working/reference performance. Overall, results indicate multiparous rats have better spatial working memory performance whereas nulliparous rats have enhanced reference performance. These results may reflect differences in neuroplasticity (with multiparous rats having more immature neurons and nulliparous rats having greater survival of new neurons) and/or stress resilience differences between the parous groups. Importantly, the influence of parity on spatial working and reference memory and acquisition was modified by ovarian hormone status. These results also suggest that the role of new neurons in cognition may be moderated by parity and ovarian status in middle age.

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