Ontogenesis of Human Cerebellar Cortex and Biopathological Characterization in Sudden Unexplained Fetal and Infant Death

Overview

Journal Virchows Arch

Specialties Cell Biology
Molecular Biology
Pathology

Date 2007 Mar 6

PMID 17334803

Citations 5

Authors

Anna Maria Lavezzi

Giulia Ottaviani

Luigi Matturri

Affiliations

Soon will be listed here.

Abstract

The aims of this study were to investigate in the human cerebellar cortex the structural and biological ontogenetic features, the possible presence of alterations in cases of sudden unexplained fetal and infant death, and the involvement of the maternal cigarette smoking in developmental abnormalities. We analyzed 52 brains of fetal and infant death victims, aged from the second gestational trimester to 12th postnatal month. In the cerebellar cortex we evaluated, besides the morphological aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, proliferating cell nuclear antigen, and apoptosis) as well as the presence of the neurotransmitter somatostatin, which is strongly implicated in central nervous system differentiation, and of EN2 gene. The observed features of the cerebellar cortex, mainly confined to the transient external granular layer, were high proliferative activity and high expression of both somatostatin and EN2 gene in prenatal life and high apoptotic index after birth. In 41% of the sudden unexplained death victims, in the greater part with smoking mothers, we observed different biopathological alterations of the cerebellar cortex. Maternal smoking is increasingly being demonstrated to be one of the main contributors to developmental neurological alterations in the offspring.

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References

Ten Donkelaar H, Lammens M, Wesseling P, Thijssen H, Renier W . Development and developmental disorders of the human cerebellum. J Neurol. 2003; 250(9):1025-36. DOI: 10.1007/s00415-003-0199-9. View

Abdel-Rahman A, Dechkovskaia A, Sutton J, Chen W, Guan X, Khan W . Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty. Toxicology. 2005; 209(3):245-61. DOI: 10.1016/j.tox.2004.12.037. View

Herrera D, Robertson H . Activation of c-fos in the brain. Prog Neurobiol. 1996; 50(2-3):83-107. DOI: 10.1016/s0301-0082(96)00021-4. View

Millen K, Hui C, Joyner A . A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum. Development. 1995; 121(12):3935-45. DOI: 10.1242/dev.121.12.3935. View

Rakic P, Sidman R . Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J Comp Neurol. 1970; 139(4):473-500. DOI: 10.1002/cne.901390407. View

Lavezzi A, Ottaviani G, Mingrone R, Matturri L . Analysis of the human locus coeruleus in perinatal and infant sudden unexplained deaths. Possible role of the cigarette smoking in the development of this nucleus. Brain Res Dev Brain Res. 2004; 154(1):71-80. DOI: 10.1016/j.devbrainres.2004.10.007. View

Vollmer J, Clerc R . Homeobox genes in the developing mouse brain. J Neurochem. 1998; 71(1):1-19. DOI: 10.1046/j.1471-4159.1998.71010001.x. View

Chen W, Edwards R, Romero R, Parnell S, Monk R . Long-term nicotine exposure reduces Purkinje cell number in the adult rat cerebellar vermis. Neurotoxicol Teratol. 2003; 25(3):329-34. DOI: 10.1016/s0892-0362(02)00350-1. View

Lavezzi A, Ottaviani G, Mauri M, Matturri L . Hypoplasia of the arcuate nucleus and maternal smoking during pregnancy in sudden unexplained perinatal and infant death. Neuropathology. 2005; 24(4):284-9. DOI: 10.1111/j.1440-1789.2004.00558.x. View

10.

Wood K, Dipasquale B, Youle R . In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron. 1993; 11(4):621-32. DOI: 10.1016/0896-6273(93)90074-2. View

11.

Laquerriere A, Leroux P, Gonzalez B, Bodenant C, TAYOT J, Vaudry H . Somatostatin receptors in the human cerebellum during development. Brain Res. 1992; 573(2):251-9. DOI: 10.1016/0006-8993(92)90770-a. View

12.

Fucile S, Renzi M, Lauro C, Limatola C, Ciotti T, Eusebi F . Nicotinic cholinergic stimulation promotes survival and reduces motility of cultured rat cerebellar granule cells. Neuroscience. 2004; 127(1):53-61. DOI: 10.1016/j.neuroscience.2004.04.017. View

13.

Olpe H, Balcar V, Bittiger H, RINK H, Sieber P . Central actions of somatostatin. Eur J Pharmacol. 1980; 63(2-3):127-33. DOI: 10.1016/0014-2999(80)90436-7. View

14.

Heck D, Sultan F . Cerebellar structure and function: making sense of parallel fibers. Hum Mov Sci. 2002; 21(3):411-21. DOI: 10.1016/s0167-9457(02)00123-9. View

15.

Fukuda K, Aihara N, Sagar S, Sharp F, Pitts L, Honkaniemi J . Purkinje cell vulnerability to mild traumatic brain injury. J Neurotrauma. 1996; 13(5):255-66. DOI: 10.1089/neu.1996.13.255. View

16.

Bautista J, Rubin S, Moran T, Schwartz G, Carbone K . Developmental injury to the cerebellum following perinatal Borna disease virus infection. Brain Res Dev Brain Res. 1995; 90(1-2):45-53. DOI: 10.1016/0165-3806(96)83485-7. View

17.

Xu F, Owen J, Frazier D . Cerebellar modulation of ventilatory response to progressive hypercapnia. J Appl Physiol (1985). 1994; 77(3):1073-80. DOI: 10.1152/jappl.1994.77.3.1073. View

18.

Matturri L, Ottaviani G, Alfonsi G, Crippa M, Rossi L, Lavezzi A . Study of the brainstem, particularly the arcuate nucleus, in sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD). Am J Forensic Med Pathol. 2004; 25(1):44-8. DOI: 10.1097/01.paf.0000113813.83779.21. View

19.

Morris G, Mathews M . Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem. 1989; 264(23):13856-64. View

20.

Gadson D, Emery J . Quantitative morphological studies of developing human cerebellar cortex in various disease states. Arch Dis Child. 1976; 51(12):964-7. PMC: 1546178. DOI: 10.1136/adc.51.12.964. View