Activation of orexin neurons through non-NMDA glutamate receptors evidenced by c-Fos immunohistochemistry.
Orexin neuropeptides participate in the regulation of feeding as well as the regulation and maintenance of wakefulness and the cognitive functions. Orexin A and B share a common precursor, prepro-orexin and neurons are localized in the lateral hypothalamus. Physiological studies showed that these neurons are regulated by glutamatergic innervations. We aimed to assess the effects of kainic acid as a potent agonist for non-NMDA glutamate receptors in the activation of orexin neurons. We also analyzed the effect of glutamate antagonist CNQX, injected prior to kainic acid, on this activation. Expression of c-Fos protein was used as a marker for neuronal activation. Dual immunohistochemical labeling was performed for prepro-orexin and c-Fos and the percentages of c-Fos-expressing orexin neurons were obtained for control, kainic acid, and CNQX groups. Kainic acid injection caused statistically significant increase in the number of c-Fos-positive neurons when compared to control group (62.69 and 36.31%, respectively). Activation of orexin neurons was blocked, in part, by CNQX (43.36%). In the light of these results, it is concluded that glutamate takes part in the regulation of orexin neurons and partially exerts its effects through non-NMDA glutamate receptors and that orexin neurons express functional non-NMDA receptors.
Department of Histology and Embryology, Uludag University Faculty of Medicine, Gorukle Kampusu, 16059 Bursa, Turkey. oeyigor@uludag.edu.tr
Ozhan
O
Eyigor
Zehra
Z
Minbay
Ilkin
I
Cavusoglu
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid