Long-term prenatal hypoxia alters maturation of brain catecholaminergic systems and motor behavior in rats.
In order to determine the influence of long-term prenatal hypoxia on the maturation of the brain catecholaminergic structures involved in motor and cognitive functions, pregnant rats were subjected to hypoxia (10% O2) from the 5th to 20th day of gestation. The in vivo activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was assessed, by accumulation of L-DOPA after i.p. administration of NSD-1015, in the motor cortex areas, the hippocampus, and the striatum at birth and at the 3rd, 7th, 14th, 21st, and 68th postnatal days. The motor reactivity to novelty and the circadian motor activity were measured at the 21st and 68th postnatal days. Exposure to prenatal hypoxia strongly altered the developmental pattern of in vivo TH activity in restricted noradrenergic terminals of the brain. In the 21-day-old prenatal hypoxic rats, the TH activity was reduced by 80% in the motor cortex areas and by 43% in the hippocampus, compared to control rats, while no differences could be detected in the striatum. Compared to control rats, the prenatal hypoxic pups exhibited a higher motor reactivity to novelty and a nocturnal motor hypoactivity at the 21st postnatal day. The neurochemical and behavioral alterations were no longer observed at the 68th postnatal day. The altered in vivo TH activity in the young rats might be part of the neural mechanisms contributing to the motor behavioral impairments induced by prenatal hypoxia. Long-term prenatal hypoxia could be linked to the development of psychopathologies that can be detected in infancy.
Perrin
David
D
Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire UMR CNRS 5123, Université Claude Bernard, Lyon, France. dav.perrin@netcourrier.com
Mamet
Julie
J
Scarna
Hélène
H
Roux
Jean Christophe
JC
Bérod
Anne
A
Dalmaz
Yvette
Y
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013995:Time; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D004791:Enzyme Inhibitors; D006834:Hydrazines; D007980:Levodopa; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase