Effect of MPEP treatment on brain-derived neurotrophic factor gene expression.
Treatment with most antidepressants induces expression of the gene coding for brain-derived neurotrophic factor (BDNF) in the hippocampus (and cerebral cortex). Recent data indicate antidepressant-like activity of group I mGlu receptor (mGluR1 and mGluR5) antagonists in animal tests/models. We now report that chronic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGlu5 receptor antagonist, increased hippocampal but reduced cortical BDNF mRNA level (Northern blot). Desipramine, a classic antidepressant, increased BDNF mRNA level in both examined brain regions. This is the first demonstration that an antagonist of mGlu5 receptors, like a majority of well-established antidepressants, induces hippocampal BDNF gene expression. A significance of MPEP ability to reduce cortical BDNF needs further study. Nevertheless, this observation further indicates a potential antidepressant activity of the group I mGlu receptor antagonists in human depression.
Legutko
Beata
B
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. nflegutk@cyf-kr.edu.pl
Szewczyk
Bernadeta
B
Pomierny-Chamioło
Lucyna
L
Nowak
Gabriel
G
Pilc
Andrzej
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors
D019208:Brain-Derived Neurotrophic Factor; C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D003891:Desipramine