抄録
Genetic transmission is suggested to be involved in the etiology of schizophrenia. Some genes and chromosomal domains have been associated with risks for the illness, although no single gene or genes have been defined as causal for this complicated illness. Individual human has one or more different sequential variations (alleles) that are determined in part by past mutations and their permanent incorporation in the genome. One frequent and non-conservative polymorphism for BDNF is a single nucleotide polymorphism (SNP) found in its pro-domain whose biological functional role remains to be fully understood. In the rodent brain, BDNF facilitate long-term potentiation in hippocampus and cortex, by enhancing synaptic transmission and vesicle docking. Therefore, we have looked for subtle cognitive and physiological differences between persons with different BDNF alleles and the underlying molecular mechanisms using several measures. Here we present our recent studies, demonstrating that different polymorphisms in the BDNF gene alter the distribution of its product, activity-dependent secretion manner, biological activity to decide neuronal survival or death, electrophysiological property to elicit synaptic transmission, and cognitive performance on an array of human brain function tests. This integrative approach is of the most importance as it suggests that a polymorphism of neuronal genes modulates cognitive performance and clinical expression of brain dysfunction. [Jpn J Physiol 55 Suppl:S56 (2005)]
