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Biomedical subjects

Julie A Markham

Publications and source records attributed to Julie A Markham.

4 recordsLinked to original sources

Corticosterone response to acute stress in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS), the most common form of inherited mental retardation, results from the silencing of the Fmr1 gene that encodes the Fragile X mental retardation protein (FMRP). Because (1) mRNA for the glucocorticoid receptor is bound by FMRP and (2) the response to acute stress is elevated in children with FXS, we examined whether this heightened response is characteristic of a mouse model of FXS. Fmr1 knockout (KO) and wildtype (WT) control mice were exposed to 30 min of acute restraint; serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60 min recovery period. Under unstressed conditions, KOs and WTs did not differ in serum corticosterone, although both genotype and sex affected corticosterone levels observed following exposure to acute stress. Similar to FXS patients, serum glucocorticoid levels of KO mice exhibited a protracted return to baseline following acute stress. This suggests that the stress response is misregulated in Fmr1 KO mice as in FXS patients and provides the first evidence for a link between a particular FMRP-binding mRNA and a functional phenotype of FXS (impaired glucocorticoid negative feedback).

Adaptation, Physiological↗

Experience-driven brain plasticity: beyond the synapse.

The brain is remarkably responsive to its interactions with the environment, and its morphology is altered by experience in measurable ways. Histological examination of the brains of animals exposed to either a complex ('enriched') environment or learning paradigm, compared with appropriate controls, has illuminated the nature of experience-induced morphological plasticity in the brain. For example, this research reveals that changes in synapse number and morphology are associated with learning and are stable, in that they persist well beyond the period of exposure to the learning experience. In addition, other components of the nervous system also respond to experience: oligodendrocytes and axonal myelination might also be permanently altered, whereas changes in astrocytes and cerebrovasculature are more transient and appear to be activity- rather than learning-driven. Thus, experience induces multiple forms of plasticity in the brain that are apparently regulated, at least in part, by independent mechanisms.

Journal Article↗

The cellular basis for volume changes in the rat cortex during puberty: white and gray matter.

We have found that developmental changes through the adolescent period in the rat cerebral cortex provide parallels to those seen in the human cortex. Like humans, the rat cerebral white matter increases during this time due to increases in the number of axons that become myelinated even while the total number of axons decreases. We have preliminary evidence that estrogen decreases the rate of myelination, which results in a sex difference in adult rats. Another parallel to the human cortex is the nonlinear changes in the size of the cortex. We have found that in some cortical regions, female rats show decreases in cortical volume and number of neurons across the time of puberty, and removal of the ovaries stops these decreases. The rat cortex may serve as a model for the cellular changes underlying the volume changes seen in adolescent humans.

Adolescent↗

Aging and sex influence the anatomy of the rat anterior cingulate cortex.

Cognitive processes supported by the prefrontal cortex undergo an age-related decline. Until very recently, nonhuman animal models of aging have relied on the exclusive use of male subjects. This study was designed to investigate the influence of age, sex, and ovarian hormonal state on anatomy of the rat medial prefrontal cortex (anterior cingulate cortex). Dendritic tree extent and spine density were examined in young adult (3-5 mos.) and aged (20-24 mos.) male and female rats. Young adult females were examined either at proestrus or estrus, and aged females were examined in one of two reproductively senescent (estropausal) phases, persistent estrus or persistent diestrus. Neither the estrous cycle nor state of estropause influenced spine density or dendritic tree extent. However, the anatomy of the anterior cingulate cortex of young adult rats was sexually dimorphic, with males having greater dendritic spine density as well as arborization. While there was a reduction in density and tree extent with age for both sexes, this reduction was more pronounced for males, resulting in a disappearance of most sex differences with age. Thus the results of this study suggest that aging of the rodent cerebral cortex may follow a sexually dimorphic pattern.

Aging↗