Abstract

Chronic hypertension is a primary risk factor of vascular dementia. The hippocampus is a brain region critical to learning and memory and is highly susceptible to hypoxia/ischemia. Here, we investigated how chronic hypertension affects two different types of memory function, and whether one sex is more susceptible to hypertension-induced memory impairment. Memory function in adult male and female SHR (spontaneously hypertensive rats) and normotensive Wistar rats was tested using two behavioral tasks (n=6/group). The radial arm maze (RAM) tested reference memory that is largely hippocampal-dependent by measuring the time it took to retrieve rewards from three baited arms during daily 10 min sessions. A continuous y maze task was used to calculate alternation index and determine working memory that is cortico-hippocampal-dependent. Data are mean±SEM and comparisons made via a two-way ANOVA with a post-hoc Tukey test. In the RAM task, female rats had steeper learning curves than males as they completed the task in less time with each session (Fig 1). There was a significant interaction between sex and hypertension in the y maze task (F (1,20) =13.26, p=0.002). Working memory was impaired in female SHR, with a lower alternation index (index=0.60±0.03) than Wistar rats (index=0.74±0.03). However, male SHR that had a higher alternation index of 0.75±0.02 compared to 0.58±0.6 in male Wistar rats. Overall, females had stronger reference memory than males regardless of hypertension. Working memory was differentially affected in male and female SHR, suggesting sex differences in the susceptibility of different brain regions and types of memory to hypertension-induced dysfunction.

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