Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia.
BACKGROUND
Altered glutamate transmission has been found in the medial temporal lobe in severe psychiatric illnesses, including major depressive disorder (MDD) and bipolar disorder (BD). The vesicular glutamate transporters (VGLUTs) have a pivotal role in presynaptic release of glutamate into the synaptic cleft. We investigated this presynaptic marker in major psychiatric illness by measuring transcript expression of the VGLUTs in the medial temporal lobe.


METHODS
The study sample comprised four groups of 13 subjects with MDD, BD, or schizophrenia (SCZ), and a comparison group from the Stanley Foundation Neuropathology Consortium. In situ hybridization was performed to quantify messenger RNA (mRNA) expression of VGLUT 1, 2, and 3 in medial temporal lobe structures. We also examined the same areas of rats treated with antidepressants, a mood stabilizer, and antipsychotics to assess the effects of these medications on VGLUT mRNA expression.


RESULTS
We found decreased VGLUT1 mRNA expression in both MDD and BD in the entorhinal cortex (ERC), decreased VGLUT2 mRNA expression in MDD in the middle temporal gyrus, and increased VGLUT2 mRNA expression in SCZ in the inferior temporal gyrus (ITG). We also found a negative correlation between age and VGLUT1 mRNA expression in BD in the ERC and ITG. We did not find any changes in VGLUT mRNA expression in the hippocampus in any diagnostic group. We found decreased VGLUT1 mRNA expression in rats treated with haloperidol in the temporal cortex.


CONCLUSIONS
These data indicate region-specific alterations of presynaptic glutamate innervation in the medial temporal lobe in the mood disorders.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
Akihito
A
Uezato
James H
JH
Meador-Woodruff
Robert E
RE
McCullumsmith
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000473:pathology*; D003024:Clozapine / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000473:pathology*; D013223:Statistics as Topic; D013702:Temporal Lobe / Q000378:metabolism*; D050496:Vesicular Glutamate Transport Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; C000715529:Msln protein, rat; D012333:RNA, Messenger; D050496:Vesicular Glutamate Transport Proteins; D000090204:Mesothelin; D003024:Clozapine; D006220:Haloperidol; D007099:Imipramine