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The Biochemistry of Brain Development and Mental Retardation

The Eleventh Blake Marsh Lecture delivered before the Royal College of Psychiatrists, 7 February, 1977

Published online by Cambridge University Press:  29 January 2018

A. N. Davison
A. N. Davison*
Affiliation:
Miriam Marks Department of Neurochemistry, Institute of Neurology, The National Hospital, Queen Square, London WC1N 3BG
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Extract

Mental retardation may be associated with a number of environmental factors such as undernutrition, lead poisoning or exposure to neuroactive drugs during a critical period of brain development. Possible biochemical mechanisms operating in these various conditions and in animal models are reviewed in relation to the vulnerable period hypothesis. Small brains are common in the mentally retarded, and this may be related to a developmental abnormality particularly at the level of the synapse.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 131 , Issue 6 , December 1977 , pp. 565 - 574
Copyright
Copyright © Royal College of Psychiatrists, 1977 

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References

Altman, J. (1970) Postnatal neurogenesis and the problem of neural plasticity. In Developmental Neurobiology (ed. Himwich, W. A.), pp 197–237. Springfield, Ill.: Thomas.Google Scholar
Balázs, R. (1974) Influence of metabolic factors on brain development. Brit. med. Bull., 30, 126–34.Google Scholar
Balázs, R. Patel, A. J. & Lewis, P. D. (1977) Metabolic influences on cell proliferation in the brain. In Biochemical Correlates of Brain Structure and Function (ed. Davison, A. N.), pp 43–83. London: Academic Press.Google Scholar
Baloh, R. W. (1973) The effects of chronic increased lead absorption on the nervous system—a review article. Bull. Los Angeles neurol. Sci., 38, 91–9.Google Scholar
Bank, N. L., Davison, A. N., Palo, J. & Savolainen, H. (1975) Biochemical studies on myelin isolated from the brains of patients with Down's syndrome. Brain, 98, 213–18.Google Scholar
Barlow, S. M., McElhatton, P. R. & Sullivan, F. M. (1975) The relation between maternal restraint and food deprivation, plasma corticosterone and induction of cleft palate in the offspring of mice. In Teratology—Trends and Applications (eds Berry, C. L. and Poswillo, D. E.), pp 97–101. New York: Springer-Verlag.Google Scholar
Beattie, A. D., Moore, M. R., Devenay, W. T., Miller, A. R. & Goldberg, A. (1972) Environmental lead pollution in an urban soft-water area. Brit. med. J., ii, 491–3.Google Scholar
Bowen, D. M., Smith, C. B., White, P. & Davison, A. N. (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain, 99, 459–96.Google Scholar
British Medical Journal (1977) Leader: Child health and environmental lead. Brit. med. J., i, 255–6.Google Scholar
Bryce-Smith, D. (1971) Lead pollution—a growing hazard to public health. Chemistry in Britain, 7, 54–6.Google Scholar
Byers, R. K. & Lord, R. E. (1943) Late effects of lead poisoning on mental development. Amer. J. Dis. Child., 66, 471–94.Google Scholar
Cavanagh, J. B. (Ed.) (1972) The Brain Unclassified Mental Retardation. Edinburgh: Churchill-Livingstone.Google Scholar
Conel, J. L. (1959) The postnatal development of the human cerebral cortex. In The Cortex of the Newborn, Vol 1. Cambridge, Mass: Harvard University.Google Scholar
Corsellis, J. A. N. (1976) Ageing and the dementias. Ch 18 in Greenfield's Neuropathology (eds Blackwood, W. and Corsellis, J. A. N.), pp 796–848. London: Edward Arnold.Google Scholar
Cragg, B. G. (1972) The development of cortical synapses during starvation in the rat. Brain, 95, 143–50.Google Scholar
Cragg, B. G. (1975) The density of synapses and neurons in normal, mentally defective and ageing human brains. Brain, 98, 81–90.Google Scholar
Cravioto, H. M., Randt, C. T., Derby, B. M. & Diaz, A. (1976) A quantitative ultrastructural study of synapses in the brains of mice following early life undernutrition. Brain Res., 118, 304–6.Google Scholar
Crome, L. & Stern, J. (1972) Pathology of Mental Retardation, 2nd Ed. Edinburgh and London: Churchill-Livingstone.Google Scholar
David, O., Clark, V. & Voeller, K. (1972) Lead and hyperactivity. Lancet, ii, 900–3.Google Scholar
David, O., Hoffman, S. P., Sverd, J., Clark, J. & Voeller, K. (1976) Lead and hyperactivity. Behavioral response to chclation: a pilot study. Amer. J. Psychiatry, 133, 10, 1155–8.Google ScholarPubMed
David, O., McGann, B., Hoffman, S., Sverd, J. & Clark, J. (1976) Low lead levels and mental retardation. Lancet, ii, 1376–9.Google Scholar
Davies, P. & Maloney, A. J. F. (1976) Selective loss of central cholinergic neurones in Alzheimer's disease. Lancet, ii, 1403.CrossRefGoogle Scholar
Davison, A. N. (1973) Nutrition and amino acid imbalance as factors influencing brain development. Ch 3 in Biochemistry and Mental Illness (eds Iversen, L. L. and Rose, S. P. R.), pp 27–37. Biochem. Soc. Spec. Publ. No. 1.Google Scholar
Dobbing, J. (1970) Undernutrition and the developing brain. The relevance of animal models to the human problem. Amer. J. Dis. Child., 120, 411–15.Google Scholar
Dobbing, J. (1974) The later development of the brain and its vulnerability. In Scientific Foundations of Paediatrics (eds Davis, J. A. and Dobbing, J.), pp 565–77. London: Heinemann.Google Scholar
Dobbing, J. Hopewell, J. W. & Lynch, A. (1971) Vulnerability of developing brain. VII. Permanent deficit of neurons in cerebral and cerebellar cortex following early mild undernutrition. Exp. Neurol., 32, 439–47.Google Scholar
Dobbing, J. & Sands, J. (1970) Timing of neuroblast multiplication in developing human brain. Nature (London), 226, 639–40.Google Scholar
Dobbing, J. & Smart, J. (1974) Vulnerability of developing brain and behaviour. Brit. med. Bull., 30, 164–8.CrossRefGoogle ScholarPubMed
Dodge, P. R., Prensky, A. L. & Feigin, R. D. (1975) Nutrition and the Developing Brain. St Louis: Mosby.Google Scholar
Drachman, D. A. & Leavitt, J. (1974) Human memory and the cholinergic system. A relationship to aging? Arch. Neurol., 30, 113–21.Google Scholar
Eccles, J. C. (1965) Possible ways in which synaptic mechanisms participate in learning, remembering and forgetting. In The Anatomy of Memory (ed. Kimble, D. P.), pp 12–87. Palo Alto, Ca.: Science and Behavior Books.Google Scholar
Eckhart, C. D., Barnes, R. H. & Levitsky, D. A. (1976) Regional changes in rat brain choline acetyl transferase and acetylcholinesterase activity resulting from undernutrition imposed during different periods of development. J. Neurochem., 27, 227–83.Google Scholar
Gaull, G. E., Tallan, H. H., Lajtha, A. & Rassin, D. K. (1975) Pathogenesis of brain dysfunction in inborn errors of amino acid metabolism. Ch 2 in Biology of Brain Dysfunction, Vol 3 (ed. Gaull, G. E.), pp 47–143. New York and London: Plenum Press.Google Scholar
Giulian, D., McEwen, B. S. & Pohorecky, A. (1974) Altered development of the rat brain serotonergic system after disruptive neonatal experience. Proc. Natl. Acad. Sci. USA, 71, 4106–10.Google Scholar
Goldstein, G. W., Asbury, A. K. & Diamond, I. (1974) Pathogenesis of lead encephalopathy. Uptake of lead and reaction of brain capillaries. Arch. Neurol., 31, 382–9.Google Scholar
Gonatas, N. K. & Moss, A. (1975) Pathologic axons and synapses in human neuropsychiatric disorders. Human Pathology, 6, 571–82.Google Scholar
Hertzig, M. E., Birch, H. G., Richardson, S. A. & Tizard, J. (1972) Intellectual levels of school children severely malnourished during the first two years of life. Pediatrics, 49, 814–24.CrossRefGoogle ScholarPubMed
Himwich, W. A. & Agrawal, H. C. (1974) Developmental biochemistry. In Mental Retardation and Developmental Disabilities, Vol 6 (ed. Wortis, J.), pp 84–107. New York: Brunner-Mazel.Google Scholar
Howard, E., Granoff, D. M. & Bujnovszky, P. (1969) DNA, RNA and cholesterol increases in cerebrum and cerebellum during development of human fetus. Brain Res., 14, 697–706.Google Scholar
Jones, D. G. & Dyson, S. E. (1976) Synaptic junctions in undernourished rat brain—an ultrastructural investigation. Exp. Neurol., 51, 529–35.Google Scholar
Krigman, M. R. & Hogan, E. L. (1976) Undernutrition in the developing rat: effect upon myelination. Brain Res., 107, 239–55.Google Scholar
Lansdown, R. G., Clayton, B. E., Graham, P. J., Shepherd, J., Delves, H. T. & Turner, W. C. (1974) Blood-lead levels, behaviour and intelligence. A population study. Lancet, i, 538–41.Google Scholar
Lewis, P. D., Balázs, R., Patel, A. J. & Johnson, A. L. (1975) The effect of undernutrition in early life on cell generation in the rat brain. Brain Res., 83, 235–47.Google Scholar
Lewis, P. D., Patel, A. J., Bendek, G. & Balázs, R. (1977) Hypothesis: no drugs acting on the nervous system affect cell proliferation in the developing brain? Lancet. In press.Google Scholar
Lim, L. (1977) Ribonucleic acid metabolism. Ch 2 in Biochemical Correlates of Brain Structure and Function (ed. Davison, A. N.), pp 15–41. London: Academic Press.Google Scholar
Lin-Fu, J. S. (1973) Vulnerability of children to lead exposure and toxicity. New Engl. J. Med., 289, 1229–33.Google Scholar
Marin-Padilla, M. (1976) Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome: a Golgi study. J. comp. Neur., 167, 63–82.Google Scholar
Nair, V. (1974) Prenatal exposure to drugs: effect on the development of brain monoamine systems. In Drugs and the Developing Brain (eds Vernadakis, A. and Weiner, N.), pp 171–97. New York: Plenum Publishing Corporation.Google Scholar
Nicholson, J. L. & Altman, J. (1972) Synaptogenesis in the rat cerebellum: effects of early hypo- and hyperthyroidism. Science, 176, 530–2.Google Scholar
Ohara, P. T. (1972) Electron microscopical study of the brain in Down's syndrome. Brain, 95, 681–4.Google Scholar
Pentschew, A. & Garro, F. (1966) Lead encephalomyelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases. Acta neuropath., 6, 266–78.Google Scholar
Perry, E., Perry, R. H., Blessed, G. & Tomlinson, B. C. (1977) Necropsy evidence of central cholinergic deficits in senile dementia. Lancet, i, 189.Google Scholar
Quimby, K. L., Aschkenase, L. J. & Bowman, R. E. (1974) Enduring learning deficits and cerebral synaptic malformation from exposure to 10 parts of Halothane per million. Science, 183, 625–7.Google Scholar
Raisman, G. & Field, P. M. (1973) Sexual dimorphism in the neuropil of the preoptic area of the rat and its dependence on neonatal androgens. Brain Res., 54, 1–29.Google Scholar
Randt, C. T. & Derby, B. M. (1973) There is persistent behavioural alteration many months after rehabilitation in previously nutritionally deprived mice. Arch. Neurol., 28, 167–72.Google Scholar
Rees, S. (1977) The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome). Acta neuropath. (Berlin), 37, 65–8.CrossRefGoogle ScholarPubMed
Shoemaker, W. J. & Wurtman, R. J. (1973) Effect of perinatal undernutrition on the metabolism of catecholamines in the rat brain. J. Nutr., 103, 1537–47.Google Scholar
Slotkin, T. A., Lau, C. & Bartolomé, M. (1976) Effects of neonatal or maternal methodone administration on ornithine decarboxylase activity in brain and heart of developing rats. J, Pharmac. exp. Ther., 199, 141–8.Google Scholar
Thomas, J. A., Dallenbach, F. D. & Thomas, M. (1973) The distribution of radioactive lead (210Pb) in the cerebellum of developing rats. J, Path., 109, 45–50.CrossRefGoogle ScholarPubMed
Thrower, S., Hall, C., Lim, L. & Davison, A. N. (1976) The selective isolation of the uterine oestradiolreceptor complex by binding to oligo(dT)-cellulose. The mediation of an essential activator in the transformation of cytosol receptor. Biochem. J., 160, 271–80.CrossRefGoogle ScholarPubMed
Whatson, T. S., Smart, J. L. & Dobbing, J. (1976) Undernutrition in early life: lasting effects on activity and social behaviour of male and female rats. Devl. Psychobiol., 9, 529–38.Google Scholar
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