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.


METHODS
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.
Paz
Rodrigo D
RD
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, 87131, USA.
Andreasen
Nancy C
NC
Daoud
Sami Z
SZ
Conley
Robert
R
Roberts
Rosalinda
R
Bustillo
Juan
J
Perrone-Bizzozero
Nora I
NI
D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid