Abstract
The monoamine and intracellular calcium systems are two major elements of nervous system functions. However, their role in human brain development is unclear. We studied the association between activity of monoamine and intracellular calcium systems during prenatal life and subsequent psychomotor performances in healthy children. We used prospective data from 247 children followed from birth through 6 y of age. Among those, 195 were examined at 9 mo using the Brunet-Lézine Scales, whereas 126 were examined at 3 y and 100 at 6 y using the McCarthy Scales of Children's Ability. A blood sample was collected from the umbilical cord to measure levels of dopamine and serotonin metabolites (homovanillic acid and 5-hydroxyindoleacetic acid, respectively) and ATPase activities (Na+K+-ATPase and Ca2+Mg2+-ATPase). The hand skill score at 6 y of age was significantly and negatively correlated with ATPase activities and with monoamine metabolite concentrations. No other cognitive score was related to biochemical measures at birth. Results were adjusted for child's sex, mother's educational level, duration of labor, and tea consumption. Composite scores of ATPase activities and monoamine metabolite concentrations measured at birth explained 29% of hand skill score variance at 6 y. Our results demonstrate the importance of prenatal factors on monoaminergic and ATPase activities in early human psychomotor development. This study also suggests that specific psychometric measures such as fine motor tests may be a better developmental measurement to correlate with biochemical factors than general cognitive scales.
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Abbreviations
- HVA:
-
homovanillic acid
- 5-HIAA:
-
5-hydroxyindoleacetic acid
- MAO:
-
monoamine oxidase
- DBH:
-
dopamine-β-hydroxylase
- GCI:
-
General Cognitive Index
References
Berger-Sweeney J, Hohmann CF 1997 Behavioral consequences of abnormal cortical development: insights into developmental disabilities. Behav Brain Res 86: 121–142
Yew DT, Chan WY 1999 Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system. Microsc Res Tech 45: 389–400
Komori H, Matsuishi T, Yamada S, Ueda N, Yamashita Y, Kato H 1999 Effect of age on cerebrospinal fluid levels of metabolites of biopterin and biogenic amines. Acta Paediatr 88: 1344–1347
Whitaker-Azmitia PM 1991 Role of serotonin and other neurotransmitter receptors in brain development: basis for developmental pharmacology. Pharmacol Rev 43: 553–561
Hadders-Algra M, Huisjes HJ, Touwen BCL 1988 Perinatal correlates of major and minor neurological dysfunction at school age: a multivariate analysis. Dev Med Child Neurol 30: 472–481
Kapucu LO, Koç E, Gucuyener K, Zenciroglu A, Atalay Y, Unlu M, Van Royen E 1998 D2 receptor imaging with iodine-123-iodobenzamide brain SPECT in infants with hypoxic-ischemic brain injury. J Nucl Med 39: 1703–1707
Lamers KJB, Wevers RA 1998 Abnormalities of biogenic amines affecting the metabolism of serotonin and catecholamines. Mult Scler 4: 37–38
Weglage J, Pietsch M, Fünders B, Koch HG, Ullrich K 1995 Neurological findings in early treated phenylketonuria. Acta Paediatr 84: 411–415
Stokes AH, Hastings TG, Vrana KE 1999 Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55: 659–665
Klinteberg B, Oreland L, Hallman J, Wirsén A, Levander SE, Schalling D 1990–91 Exploring the connections between platelet monoamine oxydase activity and behavior: relationships with performance in neuropsychological tasks. Neuropsychobiology 23: 188–196
Matthews G 1996 Neurotransmitters release. Annu Rev Neurosci 19: 219–233
Nicotera P, Bellomo G, Orrenius S 1992 Calcium-mediated mechanisms in chemically induced cell death. Annu Rev Pharmacol Toxicol 32: 449–470
Carafoli E, Brini M 2000 Calcium pumps: structural basis for and mechanism of calcium transmembrane transport. Curr Opin Chem Biol 4: 152–161
Garcia-Martin E, Gutierrez-Merino C 1996 Rate of Na+/Ca2+ exchange across the plasma membrane of synaptosomes measured using the fluorescence of chlortetracycline. Implications to calcium homeostasis in synaptic terminal. Biochim Biophys Acta 1280: 257–264
Lees GJ 1991 Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res Rev 16: 283–300
Constantino JN, Murphy DL 1996 Monoamine metabolites in “leftover” newborn human cerebrospinal fluid: a potential resource for biobehavioral research. Psychiatry Res 65: 129–142
Constantino JN, Murphy DL, Morris JA 1999 Family psychiatric history, cerebrospinal fluid monoamine metabolites, and temperament in infants. Biol Psychiatry 45: 626–632
Clarke RA, Murphy DL, Constantino JN 1999 Serotonin and externalizing behavior in young children. Psychiatry Res 86: 29–40
Rapoport JL, Pandoni C, Renfield M, Lake CR, Ziegler MG 1977 Newborn dopamine-β-hydroxylase, minor physical anomalies, and infant temperament. Am J Psychiatry 134: 676–678
Degrell I, Nagy E 1990 Correlations between cisternal CSF and plasma concentrations of HVA, MHPG, 5-HIAA, DA, and NA. Biol Psychiatry 27: 1179–1182
Amin F, Davidson M, Davis KL 1992 Homovanillic acid measurement in clinical research: a review of methodology. Schizophr Bull 18: 123–148
Sweadner KJ 1989 Isozymes of the Na/K-ATPase. Biochem Biophysic Acta 988: 185–220
El-Mallakh RS, Wyatt RJ 1995 The Na,K-ATPase hypothesis for bipolar illness. Biol Psychiatry 37: 235–244
Campagna D, Huel G, Hellier G, Girard F, Sahuquillo J, Fagot-Campagna A, Godin J, Blot P 2000 Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns. Life Sci 68: 203–215
Tang H-W, Huel G, Campagna D, Hellier G, Boissinot C, Blot P 1999 Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters. J Appl Toxicol 19: 167–172
Brunet O, Lézine I 1983 Le développement psychologique de la première enfance. EAP, Paris
McCarthy D 1976 Manuel des échelles d'aptitudes pour enfants de McCarthy M.S.C.A. Les Editions du Centre de Psychologie Appliquée, Paris
Lee HB, Comrey AL 1979 Distortions in a commonly used factor analytic procedure. Multivariate Behav Res 14: 301–321
SAS/STAT User's Guide, Version 8. SAS Institute Inc, Cary NC, 1999
Flynn JR 1994 IQ gains over time. In: Sternberg RJ (ed) Encyclopedia of Human Intelligence. Macmillan, New York, pp 617–623.
Gabriel M, Hunneman DH, Gahr M 1983 Plasma levels of catecholamine metabolites in the newborn period. Biol Neonate 44: 203–209
Oxenstierna G, Edman G, Iselius L, Oreland L, Ross SB, Sedvall G 1986 Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals: a genetic study. J Psychiatr Res 20: 19–29
Sostek AJ, Sostek AM, Murphy DL, Martin EB, Born WS 1981 Cord blood amine oxydase activities relate to arousal and motor functioning in human newborn. Life Sci 28: 2561–2568
Amin F, Seeman TE, Mohs RC, Davidson M, Knott P, Berkman LF, Albert M, Blazer D 1994 Plasma homovanillic acid and performance on motor and cognitive tasks in community-dwelling elderly: MacArthur studies of successful aging. Neuropsychopharmacology 10: 29–35
Volkow ND, Gur RC, Wang G-J, Fowler JS, Moberg PJ, Ding Y-S, Hitzemann R, Smith G, Logan J 1998 Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry 155: 344–349
Vitiello B, Jensen PS 1995 Developmental perspectives in pediatric psychopharmacology. Psychopharmacol Bull 31: 75–81
Guerini D, Garcia-Martin E, Gerber A, Volbracht C, Leist M, Merino G, Carafoli E 1999 The expression of plasma membrane Ca2+ pump isoforms in cerebellar granule neurons is modulated by Ca2+. J Biol Chem 274: 1667–1676
Zacharias DA, Strehler EE 1996 Change of plasma membrane Ca2+-ATPase splice-variant expression in response to a rise in intracellular Ca2+. Curr Biol 6: 1642–1652
Martin LJ, Brambrink A, Koehler RC, Traystman RJ 1997 Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia. J Comp Neurol 377: 262–285
Acknowledgements
The authors thank the staff of the Robert Debré Maternity Clinic for its collaboration in obtaining specimens and the mothers for their participation.
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Supported by the French Ministry of Research and Technology (Department “Biologie, Médecine et Santé, Action toxicologie”: Grant DRAEI/93037).
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Takser, L., Campagna, D., Blot, P. et al. Could Monoamine Plasma Levels and Erythrocyte Membrane ATPase Activities at Birth Be Predictive for Future Hand Performance?. Pediatr Res 54, 358–363 (2003). https://doi.org/10.1203/01.PDR.0000077484.55921.A0
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DOI: https://doi.org/10.1203/01.PDR.0000077484.55921.A0


