Alteration in the expression of exon IIC transcripts of brain-derived neurotrophic factor gene by simvastatin [correction of simvastain] in chronic mild stress in mice: a possible link with dopaminergic pathway.
We have investigated the influence of dopaminergic agents on the expression of brain-derived neurotrophic factor (BDNF) gene in relation with lipid levels in chronic mild stress (CMS). Mice subjected to CMS were treated with simvastatin (10 mg/kg, per os (orally)) along with bromocriptine (2 mg/kg, intraperitoneally (ip)), levodopa (200 mg/kg, ip), or haloperidol (0.1 mg/kg, ip) for 14 days. CMS produced a decrease in sucrose intake and an increase in serum cholesterol and triglycerides levels with a decrease in high-density lipoprotein cholesterol, which were prevented by simvastatin. This was greater when it was combined with bromocriptine or levodopa. Haloperidol significantly prevented the simvastatin-induced increase in sucrose intake but not the alterations in lipids. There was an upregulation in the expression of BDNF exon-IIA and -IIB transcripts by CMS but not the exon-IIC transcripts. Simvastatin could increase expression of exon-IIC transcripts in stressed mice. This was partially increased by bromocriptine. Haloperidol significantly prevented simvastatin-induced increase in expression of BDNF exon-IIC transcripts. The results showed a positive correlation between expression of BDNF exon-IIC transcripts and sucrose intake. In conclusion, our data suggest the involvement of lipid levels and BDNF exon-IIC transcripts in CMS-induced behaviour in mice, possibly through the dopaminergic system.
a Faculty of Pharmacy, Hemchandracharya North Gujarat University, Patan, Gujarat, India.
Digvijay G
DG
Rana
Amrutlal K
AK
Patel
Chaitanya G
CG
Joshi
Mayurdhvaj K
MK
Jhala
Ramesh K
RK
Goyal
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D005091:Exons; D006220:Haloperidol / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D015398:Signal Transduction; D019821:Simvastatin / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001971:Bromocriptine; D007980:Levodopa; D013395:Sucrose; D019821:Simvastatin; D006220:Haloperidol; D004298:Dopamine
BDNF exon II transcripts; cholesterol; cholestérol; depression; dopamine; dépression; statines; statins; transcrits de l’exon-II du BDNF