Sexual dimorphism and developmental regulation of substantia nigra function

The substantia nigra is an important brain nucleus involved in the expressi on of movement disorders and seizures. The two most common movement disorde rs affecting the substantia nigra, Parkinson's disease and Tourette syndrom e, show gender differences and age-related onset. To assess the substrates for the gender and age specificity of substantia nigra-related disorders, w e determined the functional properties of the substantia nigra gamma -amino butyric acid (GABA(A)) system along its anterior-posterior axis, using loca lized microinfusions of muscimol (a GABA(A) agonist) and susceptibility to motor seizures in rats. In the substantia nigra, there are sex specific dif ferences in the topographic segregation and functionality of GABA(A) system s. In mature male rats there are two distinct regions mediating opposite ef fects on seizures; in female rats there is only one region that can affect seizures. In the neonatal period, the presence of circulating testosterone is essential for the development of a substantia nigra region that exerts p roconvulsant effects throughout the rat's life, a unique feature of the mal e substantia nigra. The final maturation of the substantia nigra occurs in the peripubertal period, and is in part regulated by testosterone as well. The recognition of the existence of distinct sex- and age-specific substant ia nigra features can be translated into new cures of disorders affecting t he substantia nigra.