Print this page 
Sexual dimorphism in neurological disorders
Summary
We are interested in understanding the genetic factors that underlie gender differences in susceptibility to neurological disorders. We aim to test whether abnormal SRY function, and therefore abnormal regulation of dopamine, may increase the susceptibility of men to these neurological disorders such as schizophrenia, and drug addiction.
Description
Male and female brains are different in many ways. Structural difference between the male and the female brain has been long detected in numerous brain structures including areas critical to most hormonal, vegetative, emotional and reproductive responses in our behaviour.
Gender differences also exist in relation to diseased states of brain function. For example, males are more susceptible to neurological disorders such as schizophrenia, alcoholism and other drug abuse, Attention Deficit Disorder, and Tourette's syndrome.
Although the relationship of gender to the aetiology of these diseases is unclear, all these conditions have a common defect in levels of a brain chemical called dopamine.
Dopamine has many functions in the brain, including important roles in behaviour and cognition, voluntary movement, motivation and reward, mood, attention, and learning.
We have previously demonstrated that the male-specific gene SRY is localized in dopamine producing areas in the brain, such as the substantia nigra (SN) and the ventral tegmental area. We have shown that SRY controls gene transcription of TH, the rate-limiting enzyme in dopamine synthesis. Thus, we are interested in whether SRY is a factor involved in the male susceptibility to neurological disorders characterized by dopaminergic dysfunction, such as schizophrenia.
We will test this aim by determining if the function or level of SRY are altered in human post-mortem brains from schizophrenia patients. We will also assess whether altering SRY levels in the brain, using molecular and genetic approaches, reduces symptoms or prevents the development of schizophrenia using animal models.
The proposed projects will provide entirely novel and important insights into genetic factors involved in the susceptibility of men to neurological disorders, such as schizophrenia and drug addiction.
Ultimately, the outcome of this research could yield a novel genetic context into understanding sexual dimorphism in brain disorders.
Funding
-
National Institutes of Health, USA
-
Rebecca L. Cooper Medical Research Foundation
Outcomes
-
Established rodent stereotaxic surgery, including site-specific injections and cannulation of brain structures
-
Established behavioural assays for schizophrenia
Selected Publications
Lee, J. and Harley, V. Sex differences in catecholamine regulation. Bioessays. Accepted 24/1/12