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A CHANGE IN SUSCEPTIBILITY OF RAT CEREBELLAR PURKINJE CELLS TO DAMAGE BY ACETALDEHYDE DURING FETAL, NEONATAL AND ADULT LIFE
Author(s) -
PHILLIPS S. C.,
CRAGG B. G.
Publication year - 1982
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.1982.tb00313.x
Subject(s) - purkinje cell , cerebellum , fetus , in utero , medicine , gestation , endocrinology , biology , fetal alcohol syndrome , cerebellar cortex , acetaldehyde , ethanol , anatomy , pregnancy , biochemistry , genetics
Phillips S.C. & Cragg B.G. 1982 Neuropathology a id Applied Neurobiology 8, 455–463 A change in susceptibility of rat cerebellar Purkinje cells to damage by acetaldehyde during fetal neonatal and adult life The sensitivity of rat cerebellar Purkinje cells to acetaldehyde during fetal, neonatal or adult life has been assessed by histological techniques. A pregnant female rat was exposed to ethanol vapour during the last 2 weeks of gestation while metabolism of acetaldehyde was blocked by injections of disulfiram (200mg/kg) on days E14, E16, E18 and E20. Purkinje cells were counted in the offspring 5 days after birth. The number of Purkinje cells in lobes I and VIII were 52% and 42% less than age matched controls. Smaller reductions were found in lobes V and X. The weight of the cerebellum was reduced by 42%. Neonatal rats received disulfiram (40mg) on the second day after birth and were exposed to ethanol vapour during daylight hours on the third and fourth days. Purkinje cells were counted at 5 days after birth, and losses similar to those described above were found. The weight of the cerebellum was reduced by 47%. Adult male rats were exposed to ethanol vapour for 2 weeks and given disulfiram (200mg/kg) on every second day. No reduction in cerebellar weight or loss of Purkinje cells was detected. When the dura overlying the cerebellum in adult rats was superfused with acetaldehyde solutions for 1 h, a 1–6 M solution caused degeneration whereas a 0–68 M solution did not. Thus the combination of high blood ethanol and acetaldehyde levels is damaging to perinatal Purkinje cells, whereas adult cells are resistant. We found the same ranking of susceptibility with ethanol alone (Philips & Cragg, 1982a and it was surprising that the cell losses with acetaldehyde were only marginally greater than those with ethanol alone, in view of the greater neurotoxicity of acetaldehyde during acute exposure (Phillips, 1981.