The Unit on Molecules in Neurobiology for the Development of Schizophrenia (MiNDS) is part of the Section on Neuropathology in the Clinical Brain Disorders Branch which utilizes molecular biological methodologies in brain to elucidate the neurobiology and pathophysiology of schizophrenia. In collaboration with the Section of Neuropathology, we are able to obtain well-characterized human brain samples from healthy persons and those with schizophrenia, allowing us to explore the molecular neurodevelopmental changes that occur in the human brain from infancy through adulthood. Understanding normal gene expression changes may provide clues to the underlying neurobiological events that lead to behavioral changes that are associated with schizophrenia and other major mental illnesses. We have successfully charted molecular neurobiological changes in the levels of growth-related factors, such as neurotrophic factors, dopamine receptors, and hormone receptors across normal development and compared levels of these developmentally important molecules in samples from patients with schizophrenia compared to age-matched controls. It appears that the onset of psychiatric symptoms coincides with diverse molecular changes in frontal cortex gene expression and with human behavioral maturation. While 1% of the general population suffers from schizophrenia, little is known about the cause of this complex brain disorder; but we do know that there is a substantial genetic risk for developing schizophrenia that is influence by environment or neurobiological events. One way the environment impacts the genes is by changing their expression levels across time, therefore we study genes across neurodevelopment such as: 1) how ?schizophrenia? genes influence the development of brain cells; 2) how variations of the estrogen receptor impact the development and function of the cerebral cortex; and 3) how neuregulin-1 (NRG-1) in particular may change it?s expression across postnatal development and how precisely the gene is changed in patients with schizophrenia. It is our hypothesis that patients with schizophrenia fail to undergo the correct cellular and molecular changes that occur in the normal human brain during human maturation.
| Kaalund, S S; Newburn, E N; Ye, T et al. (2014) Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Mol Psychiatry 19:1258-66 |
| Montague, D; Weickert, C S; Tomaskovic-Crook, E et al. (2008) Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species. J Neuroendocrinol 20:893-903 |
| Weickert, C S; Ligons, D L; Romanczyk, T et al. (2005) Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia. Mol Psychiatry 10:637-50 |
| Law, A J; Shannon Weickert, C; Hyde, T M et al. (2004) Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain. Neuroscience 127:125-36 |
