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Biomedical subjects

H A Bimonte

Publications and source records attributed to H A Bimonte.

9 recordsLinked to original sources

Neonatal estrogen blockade prevents normal callosal responsiveness to estradiol in adulthood.

The rat corpus callosum (CC) is larger in males than females, and is responsive to hormone manipulations during development. We previously demonstrated that P25 ovariectomy (Ovx) enlarged (defeminized) adult CC, while P70 ovary transfer (OvT) counteracted this enlarging effect, resulting in smaller (feminized) CC. Since OvT females were not Ovx'd until P25, they received some neonatal estrogen (E) exposure. Behavioral data suggest that adult responsiveness to ovarian hormones depends upon prior organization by neonatal E. It has not been determined whether a similar phenomenon occurs for the feminization of brain morphology. The current experiment examined whether our previous finding of adult CC responsiveness to ovarian hormones depended upon neonatal E exposure. We investigated this by assessing the effects of P70 ovarian hormone replacement (via ovary transfer or E pellet) in females that received either (1) normal ovarian hormone exposure until P25 Ovx, or (2) the E receptor blocker tamoxifen from birth to P25 Ovx. Females receiving normal neonatal hormone exposure responded to P70 E in the female-typical manner: E reduced CC size. In contrast, females receiving neonatal E blockade responded to adult E in the opposite manner: E increased CC size. As far as we are aware, this is the first report suggesting that neonatal E exposure organizes the female brain so that it responds normally to the organizing actions of E when later exposure occurs. These findings further challenge the traditional model of female brain development, which asserts that normal female brain organization occurs by default, in the absence of gonadal hormone exposure.

Aging↗

Adult ovary transfer counteracts the callosal enlargement resulting from prepubertal ovariectomy.

The rat corpus callosum (CC) is larger in males than females, and is sensitive to hormone manipulations during development. Previous research found that, in rats, CC sensitivity to testosterone ended by postnatal day 8 (P8). In contrast, more recent findings demonstrated that CC responsivity to ovarian hormones continued at least through P70. The current experiment extends these findings by showing that the female callosum is still sensitive to ovarian hormones as late as P130, well into adulthood.

Analysis of Variance↗

Ovarian hormones can organize the rat corpus callosum in adulthood.

The rat corpus callosum (CC) is larger in males than females, and is responsive to hormone manipulations during development. Previous data suggest that CC sensitivity to testosterone ends by postnatal day 8 (P8). In contrast, responsivity to ovarian hormones extends as late as P25. The current series of experiments investigates whether ovarian hormone effects on the callosum are permanent and whether CC sensitivity to ovarian hormones extends beyond P25. We found that P70 ovariectomy (Ovx) did not affect callosal size, suggesting that ovarian hormone exposure sometime prior to P70 is sufficient to feminize the CC, and that once the callosum is feminized, the effects can not be reversed. We also found that P25 ovariectomy enlarged, or defeminized, adult female CC, whereas ovary transfer starting on P55 or P70 counteracted this enlarging effect, resulting in feminized adult CC. Thus, although a previously feminized callosum is not affected by P70 ovarian hormone removal, a not-yet feminized callosum can still be feminized after P70. These findings indicate that there is flexibility in the developmental window within which the female brain is responsive to the active feminization process initiated by ovarian hormones.

Age Factors↗

Perceptual auditory gap detection deficits in male BXSB mice with cerebrocortical ectopias.

Underlying impairments in rapid auditory processing may contribute to disrupted phonological processing, which in turn characterizes developmental language impairment (LI). Identification of a neurobiological feature of LI that is associated with auditory deficits would further support this model. Accordingly, we found that adult male rats with induced cortical malformations were impaired in rapid auditory processing. Since 40-60% of BXSB mice exhibit spontaneous focal cerebrocortical ectopias (as seen in dyslexics brains), we assessed auditory gap detection in adult male BXSB mice. Ectopic mice were significantly worse than non-ectopics in detecting a 5 ms silent gap, but were not significantly impaired at longer gap durations (10-100 ms). Our results confirm that focal cortical malformations are associated with impairments in rapid auditory processing.

Animals↗

Sex differences in vicarious trial-and-error behavior during radial arm maze learning.

We investigated sex differences in VTE behavior in rats during radial arm maze learning. Females made more VTEs than males, although there were no sex differences in learning. Further, VTEs and errors were positively correlated during the latter testing sessions in females, but not in males. This sex difference may be a reflection of differences between the sexes in conflict behavior or cognitive strategy while solving the maze.

Animals↗

Spatial ability of XY sex-reversed female mice.

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.

Animals↗

Estradiol facilitates performance as working memory load increases.

A water-escape version of the radial-arm maze was used to assess rat spatial working memory performance. Intact females and ovariectomized females receiving a physiologically low dose, physiologically moderate dose or no estradiol replacement were studied. Subjects were given seven trials a day for 12 days. Females receiving moderate dose estradiol made fewer errors than the other three groups during the latter portion of testing. As trials progressed within a session, the elements of information to be remembered increased. Assessment of individual trials revealed that when the demand on an animal's working memory system was limited to one to four elements of information, the three groups with estrogen (including intact females) maintained successful performance, whereas the ovariectomized females made more errors. However, when the demand on an animal's working memory system was increased to six elements of information, only the moderate dose estradiol females maintained successful performance. These data suggest that, although moderate levels of estradiol replacement are the most beneficial for working memory function, even low-dose estradiol replacement can act to protect working memory systems from the decline seen with the removal of ovarian hormones.

Animals↗

Lack of activational influence of ovarian hormones on the size of the female rat's corpus callosum.

The sex difference in the midsagittal area of the adult rat corpus callosum (CC) has been shown to be mediated, in part, by gonadal steroids in early development, with the sensitive period of hormone action in the female extending at least up to postnatal day 25. Given this prolonged sensitivity, the current study attempted to delineate organizational vs. activational influences of gonadal hormones on the female rat CC. In Experiment 1, callosal size was examined across the estrous cycle at 52 and 90 days of age. In Experiment 2, females were ovariectomized at 78 days and CC parameters assessed at 110 days. Last, in Experiment 3, females were ovariectomized at 78 days and sacrificed at 110 days; in addition, sham females were sacrificed during proestrus or estrus. Neither stage of estrous cycle nor adult ovariectomy affected midsagittal CC size. These results provide evidence for organizational effects of ovarian steroids on the female callosum, with the sensitive period of hormone action ending sometime between days 25 and 78.

Animals↗

In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze.

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.

Animals↗