Group II metabotropic glutamate receptor activation by agonist LY379268 treatment increases the expression of brain derived neurotrophic factor in the mouse brain.
A number of in vitro and in vivo studies using selective agonists have indicated a neuroprotective role for group-II metabotropic glutamate (mGlu2/3) receptors in various models of neuronal injury. Although an interplay among neurotrophic factors and mGlu2/3 receptors signalling system has been suggested as possible mechanism involved on neuroprotection, at present poor information are available concerning the in vivo regulation by mGlu2/3 receptors activation of specific neurotrophic factors. By using in situ hybridization and western blotting methods the aim of present study was to analyse the potential regulatory role of selective mGluR2/3 agonist LY379268 treatment on brain derived neurotrophic factor (BDNF) expression in the mouse brain. The treatment with LY379268 evidenced a significant upregulation of BDNF mRNA levels in the cerebral cortex and in the hippocampal formation with a peak at 3 h from treatment and its disappearance already at 6 h from treatment. An analysis of dose-effect curve revealed that LY379268 may significantly enhance BDNF mRNA expression already at dose of 0.250 mg/kg b.w. The upregulation of BDNF mRNA expression was followed by a significant increase of BDNF protein levels at 24 h from LY379268 treatment. These effects of LY379268 treatment on BDNF expression were restricted to neuronal cells and were blocked by the new selective mGlu2/3 receptor antagonist LY341495, suggesting a receptor specificity. Taken together these findings suggest that several previous observed neuroprotective and trophic actions of mGluR2/3 agonists treatment may be mediated, at least in the cerebral cortex and hippocampal formation, by upregulation of BDNF expression.
Di Liberto
V
V
Department of Experimental Medicine, Division of Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, Corso Tukory 129, 90134 Palermo, Italy.
Bonomo
A
A
Frinchi
M
M
Belluardo
N
N
Mudò
G
G
D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D019208:Brain-Derived Neurotrophic Factor; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C118218:LY 379268; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3