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Victoria Luine


Aging; Dendritic Spines; Memory; Olfaction


The experiences of motherhood, pregnancy, birth and postnatal care, are associated with neural and behavioral changes. Female rats undergoing multiple bouts of motherhood (multiparous) have been shown in some, but not all studies, to have a dampened HPA axis stress response, changes in some hormone levels and better performance on spatial memory tasks compared to age matched females who have not given birth (nulliparous). Moreover, some of these changes extend into old age, approximately 24 months old. Thus, parous rats provide a unique, physiological model in which to investigate neural and hormonal factors that may contribute to cognitive decline and other changes with aging. Subjects investigated were 2-4 months old nulliparous, 10-12 months old nulliparous and 10-12 months old female Fisher 344 (F344) rats. In the first study, we found nulliparous young females had significantly better spatial memory on the object placement task than the nulliparous middle-aged females and that the multiparous middle-aged females were not different from the nulliparous young or middle-aged groups. Thus parity partially mitigated the age dependent decrease in spatial memory found in nulliparous females.

No differences in anxiety between any groups were noted on the elevated plus maze (EPM). Thus, multi-parity may have long lasting effects on spatial memory, but not on anxiety. In addition, serum oxytocin levels were assessed since oxytocin is known to contribute to maternal behavior and to mood, and levels are increased during pregnancy and lactation. Circulating oxytocin did not differ between groups. Similarly, basal serum corticosterone was not different in the groups. Possible mechanisms underlying these behavioral effects were investigated by measuring dendritic spine density in the hippocampus, the prefrontal cortex and the amygdala. Apical and basal spine density in hippocampal CA1 pyramidal cells of young virgins and multiparous females was higher than in the middle-aged nulliparous females. In the prefrontal cortex, apical spine density of hippocampal cells layer II/III showed a similar pattern as the hippocampus, but no significant differences were present in basal spines. Consistent with anxiety results, there were no significant differences in spine density in the medial amygdala, an area that contributes to anxiety regulation. Thus, the preservation of spine density in parous females may contribute to the mitigation of spatial memory loss at middle age.

Because olfaction is a necessary component of maternal behavior and the olfactory bulb shares connections with memory and emotion centers, another cohort of female rats were assessed for olfactory behavior. Using an acuity task and an olfactory habituation/dis-habituation task, olfactory sensitivity was assessed. Anxiety was further investigated by testing closer to weaning of the last litter, using additional anxiety measures and assessing before other behavior test. As in the first study, no difference between groups was found on the EPM. In addition, the latency to approach an object was not different between groups. In contrast, nulliparous middle-aged females exhibited significantly more rearing compared to multiparous middle-aged females and significantly more wall climbing than nulliparous young females. Thus, some effects of parity on age-related increases in anxiety were noted. Corticosterone was lower in nulliparous middle-aged females as compared to multiparous middle-aged females following acute restraint stress indicating that multiparous middle-aged females appear to be more sensitive to restraint stress and exhibited a larger stress response.

In olfactory assessments, no differences between groups were found on the acuity task. All groups also significantly habituated to the odor, but, in habituation 3, multiparous females spent significantly less time with the presented odor compared to nulliparous young females. This result suggests that olfactory sensitivity in multiparous females is impaired compared to young nulliparous females. While there were no differences in spine density of the semi-lunar cells in layer II/III of the piriform cortex, mitral cell number in the olfactory bulb of multiparous middle-aged females was significantly lower compared to nulliparous young females. Thus, both behavioral and morphological data suggest that parity may be detrimental to olfactory sensitivity as female's age.

Overall, these results suggest that the motherhood experience confers some neuro-protective effects that attenuate some of the negative aspects of cognitive aging. Parity preserves spine density in the hippocampus and prefrontal cortex as well as spatial memory in reproductively experienced females as they age. Parity does not appear to attenuate anxiety long-term. The benefits of parity do not appear to extend to the amygdalar or semi-lunar cells of the piriform cortex. Long-term effects of parity on olfactory behavior need further investigation because the current results were inconclusive. In conclusion, parous females therefore may offer valuable insights into the aging process, could serve as a unique and useful model for studying aging in general and for understanding how reproductive experiences influence female aging.