Summary
A rat model of a mild, chronic, early postnatal hypoxia, characterized by long-term consequences in the behavioural outcome, was used to study longterm consequences in the dopaminergic system. Exposure of newborn rats to an early postnatal hypoxia (hypobaric hypoxia, 11 kPa pO2 in the inspiratory air, 2nd–10th day of life, 10 hours daily) brings about the following lasting neurochemical changes: an increased stimulated dopamine release rate from striatum slices by about 30%, an increased low affinity, high capacity dopamine uptake into striatum synaptosomes by about 100%. The critical period to produce an increased release rate of dopamine was estimated as day 2–6 postnatally. There are no long-term changes in the concentration of dopamine and its metabolites and in the tyrosine hydroxylase activity in consequences of this early postnatal hypoxia. Treatment of newborn animals with L-DOPA (10–50 μg/g body weight) previous to hypoxia normalizes the DA release rate.
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References
Bartholini G, Zivkovic B, Scatton B (1989) Dopaminergic neurons, basic aspects. In: Trendelenburg U, Weiner N (eds) Handbook of experimental pharmacology 90/II. Springer, Berlin Heidelberg New York Tokyo, pp 277–305
Berndt Ch, Henke W, Dubiel W, Gross J (1991) Kinetic evidence that the sodium-dependent high affinity and the sodium-independent low-affinity dopamine uptake are mediated by one carrier. Biomed Biochim Acta 50: 1093–1097
Bjelke B, Andersson K, Ogren SO, Bohne P (1991) Asphyctic lesion: proliferation of tyrosine hydroxylase immunoreactive nerve cell bodies in the rat substantia nigra and functional changes in dopamine neurotransmission. Brain Res 543: 1–9
Freemann GB, Gibson GE (1986) Effect of decreased oxygen on in vitro release of endogenous 3,4 dihydroxyphenylethylamine from mouse striatum. J Neurochem 47: 1924–1931
Gordon K, Statman D, Johnston MV, Robinson TE, Becker JB, Silverstein FS (1990) Transient hypoxia alters striatal catecholamine metabolism in immature brain: an in vivo microdialysis study. J Neurochem 54: 605–611
Horn AS (1990) Dopamine uptake: a review of progress in the last decade. Prog Neurobiol 34: 387–400
Justice BJ Jr, Nicolaysen LC, Michael AC (1988) Modeling the dopaminergic nerve terminal. J Neurosci Methods 22: 239–252
Kilbourne EJ, Nankova BB, Lewis EJ, McMahon A, Osaka H, Sabban DB, Sabban El (1992) Regulated expression of the tyrosine hydroxylase gene by membrane depolarization. J Biol Chem 267: 7563–7569
Lee K, Miwa S, Koshimura K, Hasegawa H, Hamahata K, Fujiwara M (1990) Effects of hypoxia on the catecholamine release, Ca++-uptake, and cytosolic free Ca++ concentration in cultured bovine adrenal chromaffm cells. J Neurochem 55: 1131–1137
Lun A, Gross J, Beyer M, Fischer HD, Wustmann Ch, Schmidt J, Hecht K (1986a) The vulnerable period of perinatal hypoxia with regard to dopamine release and behavior in adult rats. Biomed Biochim Acta 45: 619–627
Lun A, Wustmann Ch, Berndt Ch, Fischer HD, Gross J, Hecht K, Stamminger G, Schmidt J (1986b) Postnatal administration of L-DOPA normalized hypoxia-induced long-term changes in dopamine release from striatum slices and in avoidance learning. Biomed Biochim Acta 45: 1277–1283
Lun A, Gross J, Siggel H, Pohle R (1988) Concentration of hypoxanthine in both cerebrospinal fluid and brain tissue increases under intensive hypoxia only. Biol Neon 54: 195–202
Masserano JM, Vulliet PR, Tank AW, Weiner N (1990) The role of tyrosine hydroxylase in the regulation of catecholamine synthesis. In: Trendelenburg U, Weiner N (eds) Catecholamines. Springer, Berlin Heidelberg New York Tokyo, pp 427–469
Matthies HJ (1989) In search of cellular mechanisms of memory. Prog Neurobiol 32: 277–349
Odarjuk J, Hetey L, Gross J (1987) Synaptosomal uptake and release of dopamine in striatum after hypoxia. J Neurochem 48: 1115–1120
Paneth N, Stark RI (1983) Cerebral palsy and mental retardation in relation to indicators of perinatal asphyxia. Am J Obstet Gynecol 147: 960–966
Pastuszko A, Wilson DF, Erecinska M (1982) Neurotransmitter metabolism in rat brain synaptosomes: effect of anoxia and pH. J Neurochem 38: 1657–1667
Santiago M, Westerink BHC (1991) The regulation of dopamine release from nigro-striatel neurons on conscious rats: the role of somatodendritic autoreceptors. Eur J Pharmacol 204: 79–85
Seidler JF, Slotkin TA (1990) Effects of acute hypoxia on neonatal rat brain: regionally selective, long-term alterations in catecholamine levels and turnover. Brain Res Bull 24: 157–161
Shukova T (1984) Brain damage due to intrauterine asphyxia, in hypoxia of the newborn. In: Studenikin MJ, Hallmann H (eds) Medicina, Moscow, pp 157–187
Silverstein F, Buchanan K, Johnston MW (1984) Pathogenesis of hypoxic-ischemic brain injury in a perinatal rodent model. Neurosci Lett 49: 271–277
Slotkin TA, Cowdery TS, Orband L, Pachman St, Whitmore WL (1986) Effects of neonatal hypoxia in brain development in the rat: immediate and long-term biochemical alterations in discrete regions. Brain Res 374: 63–74
Synder GL, Zigmond M (1990) The effect of L-DOPA on in vitro dopamine release from striatum. Brain Res 508: 181–187
Stefanovich V, Lun A, Gross J (1988) The effect of early postnatal hyoxia on the regional cerebral utilization of glucose in adult rats. Metabol Brain Dis 3: 311–315
Trojan St (1978) Adaptation of the central nervous system to oxygen deficiency during ontogenesis. Acta Univ Carol Med Praha: 5–180
Trouvin JH, Prioux-Guyonneau M, Cohen Y, Jacquot C (1986) Rat brain monoamine metabolism and hypobaric hypoxia: a new approach. Gen Pharmacol 17: 69–73
Westerink BHC (1985) Sequence and significance of dopamine metabolism in the rat brain. Neurochem Int 7: 221–227
Wustmann Ch, Schmidt J, Ihle W, Gross J, Fischer HD (1983) Dopamine release from striatum slices of rats at different age: influence of hypoxia. Biomed Biochim Acta 42: 265–273
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Gross, J., Lun, A. & Berndt, C. Early postnatal hypoxia induces long-term changes in the dopaminergic system in rats. J. Neural Transmission 93, 109–121 (1993). https://doi.org/10.1007/BF01245341
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DOI: https://doi.org/10.1007/BF01245341