Increased Expression of Activity-dependent Genes in Cerebellar Glutamatergic Neurons of Patients with Schizophrenia

Objective: The purpose of this study was to evaluate the functional state of glutamatergic neurons in the cerebellar cortex of patients with schizophrenia.

Method: The authors measured messenger ribonucleic acid (mRNA) levels of three activity-dependent genes expressed by glutamatergic neurons in the cerebellar cortex (GAP-43, BDNF, and GABA OLE_LINK2>(A)-delta subunit) in the tissues of 14 patients with schizophrenia and 14 matched nonpsychiatric comparison subjects. Since its level of expression does not change in response to neuronal activity, gamma-aminobutyric acid(A)-alpha6 subunit mRNA was used as a control.

Results: The levels of GAP-43 and BDNF mRNAs were significantly elevated in patients with schizophrenia, and a similar finding was observed for GABA(A)-delta mRNA. In contrast, the levels of the GABA(A)-alpha6 subunit mRNA, which is expressed in cerebellar granule cells in an activity-independent manner, did not differ from comparison subjects.

Conclusions: These results suggest that glutamatergic neurons may be hyperactive in the cerebellar cortices of patients with schizophrenia.