Biology subjects

McGowan, P. O.

Publications and source records attributed to McGowan, P. O..

3 recordsLinked to original sources

bioRxiv2020

Early-life Temperature Exposure Affects Thyroid Hormone Receptor Signaling and Epigenetic Regulation of the Paraventricular Nucleus in Female Rat Pups

Early-life maternal care received has a profound effect on later-life behaviour in adult offspring and previous studies have suggested epigenetic mechanisms (e.g., DNA methylation) are involved. Changes in thyroid hormone receptor signaling might be related to differences in maternal care received and DNA methylation modifications. We investigated the effects of two factors in the maternal environment, temperature exposure (a proxy of maternal contact) and licking-like tactile stimulation, on these processes in week-old female rat pups. We assessed thyroid hormone receptor signaling by measuring circulating triiodothyronine and transcript abundance of thyroid hormone receptors and the thyroid hormone-responsive genes DNA methyltransferase 3a and oxytocin in the paraventricular nucleus of the hypothalamus. DNA methylation of the oxytocin promoter was assessed in relation to changes in thyroid hormone receptor binding. Repeated room temperature exposure was associated with a decrease in thyroid hormone receptor signaling measures relative to nest temperature exposure, while acute room temperature exposure was associated with an increase. Repeated room temperature exposure also increased thyroid hormone receptor binding and DNA methylation at the oxytocin promoter. These findings suggest that repeated room temperature exposure may affect DNA methylation levels as a consequence of alterations in thyroid hormone receptor signaling.

neuroscience↗

bioRxiv2019

Genotype Effects and Gene x Environment Interactions on Inter-Individual Licking Received and Licking Provisioning in Female Rat Offspring

In most mammals, mothers exhibit natural variations in care that propagate between generations of female offspring. However, there is limited information on genetic variation that influences this propagation. We assessed early-life maternal care received by individual female rat offspring in relation to genetic polymorphisms linked to dopaminergic activity, maternal care provisioning, and dopaminergic activity in the maternal brain. We also conducted a systematic analysis of other genetic variants potentially related to maternal behavior in our Long-Evans rat population. We found that dopamine receptor 2 (rs107017253) variation interacted with the relationship between early-life maternal care received and dopamine levels in the nucleus accumbens which, in turn, were associated with later-life maternal care provisioning. We also discovered and validated new variants that were predicted by our systematic analysis. Our findings suggest that genetic variation influences the relationship between maternal care received and maternal care provisioning, similar to findings in human populations.

neuroscience↗

bioRxiv2019

Maternal high-fat diet induces sex-specific effects on inflammatory responses to corticosterone and lipopolysaccharide challenge in adult rat offspring

BackgroundAcute elevations in endogenous corticosterone (CORT) with psychosocial stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity as a result of high-fat diet (HFD) consumption has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes in the amygdala. These findings suggest that exposure to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor such as lipopolysaccharide (LPS), a component of gram-negative bacteria, as well as acute elevated CORT. MethodsRat offspring were exposed to maternal HFD or control diet (CHD) throughout pre and postnatal development until weaning, when all offspring were provided CHD until adulthood. In adulthood, offspring were challenged with administration of exogenous CORT, to simulate an acute physiological stress, LPS, to induce an immune stress, or both. qPCR was used to measure transcript abundance of CORT receptors and downstream inflammatory genes in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioral responses to stress. ResultsHFD female offspring exhibited elevations in anti-inflammatory transcripts, whereas HFD male offspring responded with greater pro-inflammatory gene expression to simultaneous CORT and LPS administration. ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific alterations that may alter inflammatory responses in the brain, possibly as an adaptive response to basal inflammation.

neuroscience↗