THE McCARTHY LAB
Investigating the Sex Differences in the Developing Brain
The research laboratory of Margaret McCarthy PhD aims to understand the origins and mechanisms of sex differences in the brain. Sexual differentiation of the brain is a developmental process whereby physiological and behavioral phenotypes are modified to match gonadal phenotype to ensure reproductive success.
Why do we care about sex differences in the brain?
Females are more likely to:
Suffer from affective disorder (depression, anxiety, compulsion and eating disorders)
Be diagnosed with autoimmune and neuro-degenetrative disorders
Develop disorders in adolescence
Develop late on-set schizophrenia
Males are more likely to:
Be born prematurely
Suffer brain injury at birth
Have worse outcomes following injury
Be diagnosed with disorders such as autism spectrum or attention and hyperactivity disorders, which have origins in development
Exhibit speech and language deficits
Develop early on-set schizophrenia
Are males more vulnerable? Are females more resilient?
By increasing our understanding of how the brain develops differently in males and females, the McCarthy lab has revealed both naturally occurring variations and points of vulnerability for intervention in treatment of developmental neuropsychiatric disorders with a sex bias.
Using the rat species as a research model, our seminal research focuses on the influence of steroid hormones on the developing brain with a special emphasis on understanding the cellular mechanisms —that is, the numerous, novel mechanisms (including roles for prostaglandins, endocannabinoids, amino acid transmitters, and multiple enzymes) by which steroids permanently organize the developing brain differently in males and females.
Our lab has conducted some of the first studies on how steroid hormones can epigenetically imprint on the developing brain to organize differences between males and females in adult physiology and behavior. With the discovery that the feminization program of development requires suppression of the masculinization program via DNA methylation, and that steroid hormones emancipate the male gene expression profile by reducing activity of DNA methylating enzymes. Our laboratory has also investigated inflammatory and immune-mediated sex differences in the brain, sensitive periods in brain development, neurogenesis in the postnatal brain, and the role of GABA in brain differences.