Developmental changes in nicotinic receptor mRNAs and responses to nicotine in the suprachiasmatic nucleus and other brain regions

• Published in: Brain research. Molecular brain research. Vol. 66; no. 1; pp. 71 - 82
• Main Authors: O'Hara, Bruce F., Macdonald, Ellen, Clegg, Denis, Wiler, Steven W., Andretic, Rozi, Cao, Vinh H., Miller, Joseph D., Heller, H.Craig, Kilduff, Thomas S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.03.1999; Elsevier
• Subjects: Acetylcholine; Acetylcholine - physiology; Animals; Biological and medical sciences; Blotting, Northern; c- fos; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Circadian rhythm; Circadian Rhythm - physiology; DNA Probes; DNA, Complementary; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Genes, Immediate-Early - physiology; Habenula - chemistry; Habenula - cytology; In Situ Hybridization; Mice; Mice, Inbred C57BL; Neurons - chemistry; Neurons - physiology; NGFI-A; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Paraventricular Hypothalamic Nucleus - chemistry; Paraventricular Hypothalamic Nucleus - cytology; Pregnancy; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-jun - genetics; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - genetics; RNA, Messenger - analysis; Suprachiasmatic Nucleus - chemistry; Suprachiasmatic Nucleus - cytology; Vertebrates: nervous system and sense organs; Acetylcholine; NGFI-A; Circadian rhythm; c- fos; Suprachiasmatic nucleus; Rat; Rodentia; Central nervous system; Biological rhythm; Hypothalamus; Gene expression; Cholinergic receptor; Vertebrata; Mammalia; Development; Nicotinic receptor; Brain (vertebrata); Nicotine
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(99)00004-2

Our previous studies demonstrated that nicotine induces c- fos expression in the suprachiasmatic nucleus (SCN) of the rat during a narrow developmental window occurring in the perinatal period. We have extended these observations by showing that c- fos cannot be induced in the adult SCN by nicotine even during the subjective night, when phase shifts do occur. In contrast to the SCN, significant induction of c- fos and NGFI-A was observed in the medial habenula and paraventricular nucleus at all circadian times. In the fetal rat SCN we show that NGFI-A and junB are also induced by nicotine, but not c- jun. To investigate whether changes in nicotinic acetylcholine receptor (nAChR) expression in the SCN may underlie this change in sensitivity during the perinatal period, we examined nAChR mRNAs across this developmental period. By Northern analyses, α2, α3 and α4 subunit mRNAs are relatively abundant in the fetal SCN but decline substantially in the adult. α7 mRNA increases substantially while β2 mRNA is relatively abundant throughout development. We also examine expression in the whole mouse brain beginning at embryonic day 11. Many mRNA sizes for nAChR subunits in both the rat and mouse are characterized here for the first time by Northern analyses and some show very large changes in expression across development. In particular, a small 1.4 kb α2-related mRNA is highly expressed during early development, perhaps indicating an important novel function for this subunit.