Alterations of sex-typical microanatomy: prenatal stress modifies the structure of medial preoptic area neurons in rats.

Prenatal stress disrupts normal sexual differentiation and behavior with concomitant alterations in brain development; however, its effects on the cytoarchitecture of neurons in the sexually dimorphic medial preoptic area (mPOA) of the hypothalamus is not known. Morphometric analysis of the mPOA of adult rats showed sex differences as neurons from control females had significantly greater numbers of basal dendritic branches and cumulative basal dendritic length as compared to control male neurons. Prenatal stress significantly altered these sexual dimorphisms, as prenatally stressed (P-S) males had increased measures of cell body area, perimeter, cumulative basal dendritic length, and branch point numbers as compared to control males. Prenatal stress also altered the cytoarchitecture in the female mPOA neurons as P-S female neurons had significantly greater measures for primary dendritic branch number and a trend towards significance for several additional measures as compared to control females. Therefore, there are significant effects of both sex and prenatal stress on neuronal architecture in the mPOA that may help to explain the well-documented alterations in reproductive behaviors observed in P-S animals.

Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines.

Short-term fluctuations in steroid hormones such as estradiol (E2) and progesterone (P) can affect the concentration of hippocampal dendritic spines in adult, cycling nulliparous female rats. Pregnancy is characterized by a significantly longer duration of substantially elevated E2 and P compared to the estrous cycle. Thus, even greater changes than those reported during estrus may be evident. In two experiments, we examined the extent to which reproductive and hormonal state altered the concentration of apical neuronal dendritic spines of the CA1 region of the hippocampus in the following age-matched groups (N's = 7-10/group) of rats: in Exp. 1., CA1 dendritic spine density was examined in nulliparous diestrus (DES), proestrus (PRO), and estrus (ES) females, and late-pregnant (LP) (day 21) and lactating (day 5-6; LACT) females. In Exp. 2, the effects on spine density of a regimen mimicking pregnancy (and that stimulates maternal behavior) were examined, using ovariectomized, no hormone-exposed (OVX-minus) vs. sequential P&E(2)-treated (OVX + P&E2) groups. For both experiments, brains were removed, Golgi-Cox-stained and the most lateral tertiary branches of the apical dendrite of completely-stained hippocampal CA1 pyramidal neurons were traced with oil-immersion at x 1600 and dendritic spine density (# spines/10 micro dendritic segment) recorded. In Exp. 1, spine density was increased in LP and LACT females (which were not different) compared to the other virgin groups, including PRO females, who had more spines than DES and ES. In Exp. 2, OVX + P&E2 displayed significantly more dendritic spines per 10 micro than OVX-minus females (and had numbers that were similar to those of LP and LACT from Exp. 1). Pregnancy and its attendant hormonal fluctuations, therefore, may alter hippocampal neurons that regulate some non-pup-directed components of maternal behavior (e.g., nest building) or behaviors that support maternal behavior (e.g., foraging, associative memory).

Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat.

The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.