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Synaptic Dysgenesis

Published online by Cambridge University Press:  18 September 2015

L.E. Becker*
Affiliation:
Division of Neuropathology, Department of Pathology, University of Toronto and The Hospital for Sick Children, Toronto
*
Department of Pathology (Neuropathology), The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8
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Abstract:

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Synapse formation is a complex, incompletely understood process that has received only limited investigation in man despite the importance of synaptic dysfunction in common disorders such as epilepsy and mental retardation. This review explores synaptic differentiation, focussing on the morphologic maturation of synapses. Since differentiation depends on many antecedent developmental events, synaptogenesis can be affected by several factors: errors in neuronal proliferation, migration, and differentiation. The challenge to the neurobiologist is to detect and evaluate the minor alterations in neuronal differentiation that could account for the structural basis of the clinical manifestations. Trisomy 21 is an example of a condition in which the cytoarchitecture of the cerebral cortex is not obviously altered, yet mental retardation is consistently present; research neurobiologic techniques are making possible documentation of its structural basis. Epilepsy is another example in which examination of surgically removed cerebral cortex reveals subtle cortical dysplasias helpful in understanding the basis for the abnormal electrical discharge. Further exploration of synaptogenesis, particularly the influence of gene products and epigenetic factors on synapse maturation, will increase our understanding of the pathogenesis of conditions in which “morphology” seems normal but function is abnormal.

Type
Symposium
Copyright
Copyright © Canadian Neurological Sciences Federation 1991

References

1.Vaughn, JE. Fine structure of synaptogenesis in the vertebrate cen-tral nervous system. Synapse 1989; 3: 225285.CrossRefGoogle Scholar
2.Rager, G. Morphogenesis and physiogenesis of the retino-tectal connection in the chicken. II. The retino-tectal synapses. Proc R Soc Lond [Biol] 1976; 192: 353370.Google ScholarPubMed
3.Blue, ME, Parnavelas, JG. The formation and maturation of synapses in the visual cortex of the rat. I. Qualitative analysis. J Neuro-cytol 1983; 12: 599616.Google ScholarPubMed
4.Bunge, MB. Fine structure of nerve fibres and growth cones of iso-lated sympathetic neurons in culture. J Cell Biol 1973: 56: 713735.CrossRefGoogle Scholar
5.Jones, DG. Development, maturation and aging of synapses. In: Advances in Cellular Neurobiology, Vol 4. Federoff S and Hertz L, eds. New York: Academic Press, 1983; 163222.Google Scholar
6.Steward, O, Falk, PM. Protein-synthetic machinery at postsynaptic sites during synaptogenesis: A quantitative study of the associa-tion between polyribosomes and developing synapses. J Neurosci 1986; 6: 412423.CrossRefGoogle Scholar
7.Hinds, JW, Hinds, PL. Synapse formation in the mouse olfactory bulb. II. Morphogenesis. J Comp Neurol 1976; 169: 4161.CrossRefGoogle ScholarPubMed
8.Takashima, S, Mito, T, Becker, LE. Neuronal development in the medullary reticular formation in sudden infant death syndrome and premature infants. Neuropediatrics 1985; 16: 7679.CrossRefGoogle ScholarPubMed
9.Weber, ED, Stelzner, DJ. Synaptogenesis in the intermediate gray region of the lúmbar spinal cord in the postnatal rat. Brain Res 1980; 185: 1737.CrossRefGoogle ScholarPubMed
10.Scheibel, ME, Davies, TL, Scheibel, AB. Maturation of reticular dendrites: Loss of spines and development of bundles. Exp Neurol 1973; 38: 301310.CrossRefGoogle ScholarPubMed
11.Morest, DK. The growth of dendrites in the mammalian brain. Z Anat Entwicklungsgesch 1969; 128: 290317.CrossRefGoogle ScholarPubMed
12.Henrikson, CK, Vaughn, JE. Fine structural relationships between neurites and radial glial processes in developing mouse spinal cord. J Neurocytol 1974; 3: 659675.CrossRefGoogle ScholarPubMed
13.Hayes, BP, Roberts, A. The distribution of synapses along the spinal cord of an amphibian embryo: An electron microscope study of junction development. Cell Tissue Res 1974; 153: 227244.CrossRefGoogle ScholarPubMed
14.Rees, RP, Bunge, MB, Bunge, RP. Morphological changes in the neuritic growth cone and target neuron during synaptic junction development in culture. J Cell Biol 1976; 68: 240263.CrossRefGoogle ScholarPubMed
15.Gotow, T, Sotelo, C. Postnatal development of the inferior olivary complex in the rat: IV. Synaptogenesis of GABAergic afferents. analyzed by glutamic acid decarboxylase immunocytochemistry. J Comp Neurol 1987; 263: 526552.CrossRefGoogle ScholarPubMed
16.Westenbroek, RE, Westrum, LE, Hendrickson, AE, et al. Ultrastructural localization of immunoreactivity in the developing piriform cortex. J Comp Neurol 1988; 274: 319333.CrossRefGoogle ScholarPubMed
17.Edelman, GM. Cell-surface modulation and marker multiplicity in neural patterning. Trends Neurosci 1984; 7: 7884.CrossRefGoogle Scholar
18.Caviness, VS Jr, So, DK, Sidman, RL. The hybrid reeler mouse. J Hered 1972; 63: 241246.CrossRefGoogle ScholarPubMed
19.Lauder, JM. Hormonal and humoral influences on brain development. Psychoneuroendocrinology 1983; 8: 121155.CrossRefGoogle ScholarPubMed
20.Scott, BS, Petit, TL, Becker, LE, et al. Electric membrane properties of human DRG neurons in cell culture and the effect of high K medium. Brain Res 1979; 178: 529544.CrossRefGoogle ScholarPubMed
21.Scott, BS, Petit, TL, Becker, LE, et al. Abnormal electric membrane properties of Down’s syndrome DRG neurons in cell culture. Brain Res 1981; 254: 257270.CrossRefGoogle ScholarPubMed
22.Scott, BS, Becker, LE, Petit, TL. Neurobiology of Down’s syndrome. Prog Neurobiol 1983; 21: 199237.CrossRefGoogle ScholarPubMed
23.Petit, TL, LeBoutillier, JC, Alfano, DP, et al. Synaptic development in the human fetus: A morphometric analysis of normal and Down’s syndrome neocortex. Exp Neurol 1984; 83: 1323.CrossRefGoogle ScholarPubMed
24.Purpura, DP. Normal and aberrant neuronal development in the cerebral cortex of human fetus and young infants. In: Buchwald, NA, Brazier, MAB, eds. Brain Mechanisms in Mental Retardation. New York: Academic Press, 1975; 141169.CrossRefGoogle Scholar
25.Takashima, S, Chan, F, Becker, LE, et al. Morphology of the developing visual cortex of the human infant. A quantitative and qualitative Golgi study. J Neuropathol Exp Neurol 1980; 39: 487501.CrossRefGoogle ScholarPubMed
26.Takashima, S, Becker, LE, Armstrong, DL, et al. Abnormal neuronal development in the visual cortex of the human fetus and infant with Down’s syndrome. A quantitative and qualitative Golgi study. Brain Res 1981; 225: 121.CrossRefGoogle ScholarPubMed
27.Becker, LE, Armstrong, DL, Chan, F. Dendritic atrophy in children with Down’s syndrome. Ann Neurol 1986; 20: 520526.CrossRefGoogle ScholarPubMed
28.Jagadha, V, Becker, LE. Dendritic pathology: An overview of Golgi studies in man. Can J Neurol Sci 1989; 16: 4150.CrossRefGoogle ScholarPubMed
29.Becker, LE, Jagadha, V. Structural adaptations of dendrites in the human brain during development and disease. In: Petit, TL, Ivy, GO, eds. Neural Plasticity: A Lifespan Approach. New York: Alan R. Liss, Inc. 1988; 4367.Google Scholar
30.Takashima, S, leschima, A, Nakamura, H, et al. Dendrites, dementia and the Down syndrome. Brain Dev 1989; 11: 131133.CrossRefGoogle ScholarPubMed
31.Becker, LE, Takada, K. Structural malformations of the cerebral hemispheres. In: Hoffman, HJ, Epstein, F, eds. Disorders of the Developing Nervous System: Diagnosis and Treatment. Boston: Blackwell Scientific Publications Inc. 1986; 191223.Google Scholar
32.Takashima, S, Becker, LE, Chan, F, et al. A Golgi study of the cerebral cortex in Fukuyama-type congenital muscular dystrophy, Walker-type “lissencephaly”, and classical lissencephaly. Brain Develop 1987; 9: 621626.CrossRefGoogle Scholar
33.Takada, K, Becker, LE, Chan, F. Aberrant dendritic development in the human agyric cortex: a quantitative and qualitative Golgi study of two cases. Clin Neuropathol 1988; 7: 111119.Google ScholarPubMed
34.Takashima, S, Becker, LE. Basal ganglia calcification in Down’s syndrome. J Neurol Neurosurg Psychiatry 1985; 48: 6164.CrossRefGoogle ScholarPubMed
35.Shah, SN. Fatty acid composition of lipids of human brain myelin and synaptosomes: Changes in phenylketonuria and Down’s syndrome. Int J Biochem 1979; 10: 477482.CrossRefGoogle ScholarPubMed
36.Molliver, ME, Kostovic, I, van der Loos, H. The development of synapses in cerebral cortex of the human fetus. Brain Res 1973; 50: 403407.CrossRefGoogle ScholarPubMed
37.Kish, S, Karlinsky, H, Becker, L, et al. Down’s syndrome individuals begin life with normal levels of brain cholinergic markers. J Neurochem 1989; 52: 11831187.CrossRefGoogle ScholarPubMed
38.Brooksbank, BWL, Walker, D, Balazs, R, et al. Neuronal maturation in the foetal brain in Down’s syndrome. Early Human Develop 1989; 18: 237246.CrossRefGoogle ScholarPubMed
39.Marin-Padilla, M. Pyramidal cell abnormalities in the motor cortex of a child with Down’s syndrome: A Golgi study. J Comp Neurol 1976; 167: 6381.CrossRefGoogle ScholarPubMed
40.Suetsugu, M, Mahraein, P. Spine distribution along the apical dendrites of the pyramidal neurons in Down’s syndrome: A quantitative Golgi study. Acta Neuropathol (Berl) 1980; 50: 207210.CrossRefGoogle ScholarPubMed
41.Coyle, JT, Oster-Granite, ML, Gearhart, JD. The neurobiologic consequences of Down syndrome. Brain Res Bull 1986; 16: 773787.CrossRefGoogle ScholarPubMed
42.Allore, R, O’Hanlon, D, Price, R, et al. Gene encoding the β subunit of SI00 protein is on chromosome 21: Implications for Down syndrome. Science 1988; 239: 13111313.CrossRefGoogle Scholar
43.Griffin, WST, Stanley, LC, Ling, C, et al. Brain interleukin I and S- 100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 1989; 86: 76117615.CrossRefGoogle ScholarPubMed
44.Moreland, DB, Glasauer, FE, Egnatchik, JG, et al. Focal cortical dysplasia. Case Report. J Neurosurg 1988; 68: 487490.CrossRefGoogle ScholarPubMed
45.Sutula, T, Cascino, G, Cavazos, J, et al. Mossy fibre synaptic reorganization in the epileptic human temporal lobe. Ann Neurol 1989; 26: 321330.CrossRefGoogle ScholarPubMed
46.Drake, J, Hoffman, HJ, Kobayashi, J, et al. Surgical management of children with temporal lobe epilepsy and mass lesions. Neurosurgery 1987; 21: 792797.CrossRefGoogle ScholarPubMed
47.Meencke, HJ. The density of dystopic neurons in the white matter of the gyrus frontalis inferior in epilepsies. J Neurol 1983; 230: 171181.CrossRefGoogle ScholarPubMed
48.Meencke, HJ, Janz, D. The significance of microdysgenesia in primary generalized epilepsy: an answer to the considerations of Lyon and Gastaut. Epilepsia 1985; 26: 368371.CrossRefGoogle Scholar
49.Hardiman, O, Burke, T, Phillips, J, et al. Microdysgenesis in resected temporal neocortex: Incidence and clinical significance in focal epilepsy. Neurology 1988; 38: 10411047.CrossRefGoogle ScholarPubMed
50.Kaufmann, WE, Galaburda, AM. Cerebrocortical microdysgenesis in neurologically normal subjects: A histopathologic study. Neurology 1989; 39: 238244.CrossRefGoogle ScholarPubMed
51.Townsend, JJ, Nielsen, SL, Malamud, N. Unilateral megalencephaly: Hamartoma or neoplasm? Neurology 1975; 25: 448453.CrossRefGoogle ScholarPubMed
52.Bignami, A, Palladini, G, Zappella, M. Unilateral megalencephaly with nerve cell hypertrophy. An anatomical and quantitative his-tochemical study. Brain Res 1968; 9: 103114.CrossRefGoogle ScholarPubMed
53.Manz, HJ, Phillips, TM, Rowden, G, et al. Unilateral megalen-cephaly, cerebral cortical dysplasia, neuronal hypertrophy, and heterotopia: cytomorphometric, fluorometric cytochemical, and biochemical analyses. Acta Neuropathol (Berl) 1979; 45: 97103.CrossRefGoogle ScholarPubMed
54.Nakamura, Y, Becker, LE. Subependymal giant-cell tumor: Astro-cytic or neuronal? Acta Neuropathol (Berl) 1983; 60: 271277.CrossRefGoogle ScholarPubMed
55.Vinters, HV, Fisher, RS, Orloff, W, et al. Cerebral cortical dysplasia and hamartomas in pediatric epilepsy: immunohistochemical study. (Abstract) J Neurpathol Exp Neurol 1990; 49: 305.CrossRefGoogle Scholar
56.Falconer, MA, Cavanagh, JB. Clinico-pathological considerations of temporal lobe epilepsy due to small focal lesions. Brain 1959; 82: 483504.CrossRefGoogle ScholarPubMed
57.Daumas-Duport, C, Scheithauer, BW, Chodkiewicz, JP, et al. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery 1988; 23: 545556.CrossRefGoogle ScholarPubMed
58.Koeppen, AH, Mitzen, EJ, Hans, MB, et al. Olivopontocerebellar atrophy: Immunocytochemical and Golgi observations. Neuro-logy 1986; 36: 14781488.CrossRefGoogle ScholarPubMed
59.Burnham, WM, Hwang, PA, Hoffman, HJ, et al. Benzodiazepine receptor binding in human epileptogenic cortical tissue. In: Engel, J Jr, ed. Fundamental Mechanisms of Human Brain Function. New York: Raven Press, 1987. 227235.Google Scholar