Up-regulation of the GPR39 Zn2+-sensing receptor and CREB/BDNF/TrkB pathway after chronic but not acute antidepressant treatment in the frontal cortex of zinc-deficient mice.
BACKGROUND
The GPR39-Zn(2+)-sensing receptor seems to be involved in the pathophysiology of depression. GPR39 knockout animals show depressive- and anxiety-like behavior. Chronic treatment with selective antidepressants (ADs) up-regulates GPR39.


OBJECTIVE
In the present study we investigated whether acute or chronic treatment with imipramine, escitalopram, reboxetine and bupropion would cause changes in CREB, BDNF, TrkB and GPR39-Zn(2+) receptor proteins (measured by Western Blot) in the frontal cortex of mice fed with a low-zinc diet.


RESULTS
The administration of acute antidepressants induced diverse effects in the proteins that were examined (namely, GPR39 down-regulation and a reduction in CREB protein after administration of all ADs; a decrease in BDNF after administration of imipramine and escitalopram; an increase in BDNF after administration of reboxetine; no change in BDNF following administration of bupropion; and a decrease in TrkB following the administration of all ADs except bupropion). On the other hand, chronic treatment (which is required for depression relief) with all antidepressants increased the levels of all these proteins.


CONCLUSIONS
The present study for the first time demonstrates the up-regulation of GPR39 (and CREB, BDNF, and TrkB) protein when induced by chronic treatment with antidepressants (with different pharmacological profiles) in a zinc-deficiency model in mice. These data further indicate that the GPR39 receptor may be an important target in the antidepressant response.
Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland; Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: katarzyna.mlyniec@uj.edu.pl.
Katarzyna
K
Młyniec
Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland; Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Gabriel
G
Nowak
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D000077593:Reboxetine; D020813:Receptor, trkB / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D015032:Zinc / Q000172:deficiency*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; C495797:GPR39 protein, human; D009025:Morpholines; D043562:Receptors, G-Protein-Coupled; D016642:Bupropion; D015283:Citalopram; D000077593:Reboxetine; D020813:Receptor, trkB; D015032:Zinc; D007099:Imipramine
Antidepressants; BDNF; CREB; GPR39; Zinc deficiency