The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum

Abstract

We have previously shown that exposing rats to a high dose of ethanol on postnatal d 5 can affect Purkinje cell numbers in the cerebellum whilst similar exposure on d 10 had no such effect. The question arose whether a longer period of ethanol exposure after d 10 could produce loss of Purkinje cells. We have examined this question by exposing young rats to a relatively high dose (" 420-430 mg\dl) of ethanol for 6 d periods between the ages of either 4 and 9 d or 10 and 15 d of age. Exposure was carried out by placing the rats in an ethanol vapour chamber for 3 h per day during the exposure period. Groups of ethanoltreated (ET), separation controls (SC) and mother-reared controls (MRC) were anaesthetised and killed when aged 30 d by perfusion with buffered 2n5 % glutaraldehyde. Stereological methods were used to determine the numbers of Purkinje cells in the cerebellum of each rat. MRC, SC and rats treated with ethanol between 10-15 d of age each had, on average, about 254-258 thousand cerebellar Purkinje cells ; the differences between these various groups were not statistically significant. However, the rats treated with ethanol vapour between 4-9 d of age had an average of only about 128 000p20 000 Purkinje cells per cerebellum. This value was significantly different from both the MRC and group-matched SC animals. It is concluded that the period between 4 and 9 d of age is an extremely vulnerable period during which the rat cerebellar Purkinje cells are particularly susceptible to the effects of a high dose of ethanol. However, a similar level and duration of ethanol exposure commencing after 10 d of age has no significant effect on Purkinje cell numbers.

Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex

“…They 29) speculated that maternal deprivation might have greater effects on the immature brain, which may be more susceptible to cell death prior to the establishment of neural connections. The results of our previous study 28) seem to be inconsistent with that of Zhang's group 29) . This discrepancy might have arisen from differences in the timing and/or period of separation and the methodology employed.…”

“…Early postnatal maternal separation for 3 h each day from PND10 to PND15 showed no significant changes in the total number of cerebellar Purkinje cells between separated and control rats when they were examined on PND 16 and 30. Similarly, an identical duration of maternal separation from PND4 to 9 showed no significant changes in the total number of Purkinje cell numbers when assessed on PND10 and PND30 28) . These lines of evidence indicate that cerebellar Purkinje cells are less influenced by early postnatal repeated maternal separation stress.…”

“…Such developmental features are highly involved in the differential alterations of various neurotrophic factors in the cerebellum, hippocampus, and cerebral cortex. We have previously examined the effects of early postnatal maternal separation on the total number of cerebellar Purkinje cells in rats with stereological techniques 28) . Early postnatal maternal separation for 3 h each day from PND10 to PND15 showed no significant changes in the total number of cerebellar Purkinje cells between separated and control rats when they were examined on PND 16 and 30.…”

Eyeblink Classical Conditioning and Interpositus Nucleus Activity Are Disrupted in Adult Rats Exposed to Ethanol as Neonates

“…More recent studies have confirmed and extended these findings using unbiased stereological procedures, in which estimates of the total number of cells in a structure are not affected by changes in cell density (Napper and West 1995a;Pauli et al 1995;Goodlett and Lundahl 1996;Goodlett and Eilers 1997;Miki et al 1999). Cell loss is greatest during the early stages of Purkinje cell dendritic outgrowth and synap-togenesis (which occurs in rats on postnatal days [PDs] 4-9).…”

Ethanol exposure of neonatal rats does not increase biomarkers of oxidative stress in isolated cerebellar granule neurons

“…A particular feature of this neurotoxicity is the differential temporal vulnerability of neuronal loss. When ethanol exposure occurs during the period postnatal day (P) 4-6, significant loss of neurons occurs reproducibly in the cerebellum (Goodlett and Eilers, 1997;Hamre and West, 1993;Miki et al, 1999;Pierce et al, 1999). In contrast, the periods prior to P4 and after P6 are less sensitive to ethanol neurotoxicity.…”