Evidence for the involvement of heme oxygenase-1 in the antidepressant-like effect of zinc.
BACKGROUND
Considering that heme oxygenase-1 (HO-1) and the brain-derived neurotrophic factor (BDNF)-mediated pathway are involved in the pathophysiology of depression and that zinc has been shown to exert beneficial effects in the management of depression, this study investigated the influence of these targets on the antidepressant-like effect of zinc.


METHODS
Mice were treated with sub-effective or effective doses of zinc chloride (ZnCl2, 10mg/kg, po), and 45min later, they received intracerebroventricular (icv) injections of sub-effective doses of either zinc protoporphyrin IX (ZnPP, 10μg/mouse, HO-1 inhibitor), cobalt protoporphyrin IX (CoPP, 0.01μg/mouse, HO-1 inducer) or K-252a (1μg/mouse, TrkB receptor antagonist). Immobility time and locomotor activity were evaluated through the tail suspension test (TST) and open-field test (OFT), respectively. HO-1 immunocontents were evaluated in the prefrontal cortex and hippocampus 60min after ZnCl2(10mg/kg, po) treatment.


RESULTS
The antidepressant-like effect of ZnCl2was prevented by the treatment with ZnPP and K-252a. Furthermore, sub-effective doses of CoPP and ZnCl2produced a synergistic antidepressant-like effect in the TST. None of the treatments altered locomotor activity. ZnCl2administration increased HO-1 immunocontents only in the prefrontal cortex.


CONCLUSIONS
The results indicate that the antidepressant-like effect of ZnCl2in the TST may depend on the induction of HO-1, and activation of TrkB receptor.
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Luana M
LM
Manosso
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Morgana
M
Moretti
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Julia M
JM
Rosa
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Mauricio P
MP
Cunha
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil. Electronic address: alsrodri@gmail.com.
Ana Lúcia S
ALS
Rodrigues
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D002712:Chlorides; D026121:Indole Alkaloids; D011524:Protoporphyrins; D017967:Zinc Compounds; C017803:zinc protoporphyrin; C007095:cobaltiprotoporphyrin; C016837:zinc chloride; C049985:staurosporine aglycone; D051547:Heme Oxygenase-1
Antidepressant; Brain-derived neurotrophic factor; Heme oxygenase-1; Tail suspension test; Zinc