Perinatal nicotine attenuates the hypoxia-induced up-regulation of tyrosine hydroxylase and galanin mRNA in locus ceruleus of the newborn mouse.
The effect of perinatal nicotine exposure on the hypoxic response in the newborn mouse was examined, with special reference to the catecholaminergic system. We studied transcripts for the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) and the neuropeptide galanin (GAL) in locus ceruleus (LC) and adrenal medulla at different times after birth and postnatal hypoxia. We thereafter investigated how perinatal nicotine affected these mRNA levels, as well as the ability of the newborn to survive severe hypoxia. TH mRNA levels increased postnatally in both LC and adrenals, reaching peak values at 24 h postnatally and thereafter stabilizing at lower levels. GAL mRNA also increased in the LC but did not decrease after 24 h. Acute hypoxia (5% O(2) for 60 min) elicited increases in TH and GAL mRNA levels in the LC after 24 h. However, TH mRNA levels in the adrenals did not change. Perinatal nicotine exposure increased mortality after hypoxia (from 0% to 16.9%). Moreover, hypoxia-induced increases in TH and GAL mRNA levels in the LC were not observed in nicotine-treated pups. Nicotine also decreased basal TH mRNA levels in the adrenals. The present results suggest (1) that the postnatal increases in adrenal TH mRNA levels are not directly due to hypoxia at birth, and (2) that the increased mortality seen after hypoxia in nicotine pups concurs with a perturbed LC function in these animals. A deficient catecholamine synthesis in the adrenals may also contribute to the detrimental effect of prenatal exposure to nicotine on the response to hypoxia.
Wickström
H Ronny
HR
Department of Woman and Child Health, Karolinska Institutet, 171 77 Stockholm, Sweden. ronny.wickstrom@kbh.ki.se
Mas
Christophe
C
Simonneau
Michel
M
Holgert
Hans
H
Hökfelt
Tomas
T
Lagercrantz
Hugo
H
D000208:Acute Disease; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine