Acute exposure to alcohol during early postnatal life causes a deficit in the total number of cerebellar Purkinje cells in the rat

Abstract

Alcohol taken regularly over a lengthy period of time has been claimed to cause the loss of neurons in both the adult and developing brain. However, it remains uncertain whether acute, as opposed to chronic, exposure to alcohol at specified periods can also cause disruption in the neuronal population of the developing brain. This question was investigated by exposing Wistar rat pups to 7.5 g/kg body weight of ethanol administered as a 10% solution via an intragastric cannula over an 8 hour period either on the 5th (PND5) or the 10th (PND10) postnatal day of age. Gastrostomy controls received a 5% sucrose solution substituted isocalorically for the ethanol. Another set of pups raised by their mothers was used as "suckle controls." All surgical procedures were carried out under halothane vapour anaesthesia. After the artificial feeding regimes, all pups were returned to the lactating dams and weaned at 21 days of age. Between 52 and 54 days of age, the rats were anaesthetised with an intraperitoneal injection with Nembutal and killed by intracardiac perfusion with 3% glutaraldehyde in 0.1 M phosphate buffer. The relatively unbiased stereological procedure known as the "fractionator" method was used to estimate the total number of Purkinje cells in the cerebellum of each animal. The Purkinje cell nucleolus was used as the counting unit; it was assumed that each Purkinje cell contained only one nucleolus. PND10 ethanol-treated rats and gastrostomy and suckle controls had between about 210,000-232,000 Purkinje cells in the cerebellum. However, the PND5 ethanol-treated rats had only about 137,000 Purkinje cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

“…In addition to the IP, rat neonates exposed to ethanol also have dramatic reductions in the total estimated number of Purkinje cells in the cerebellar cortex Pauli et al, 1995;Thomas et al, 1998;Tran et al, 2005), an effect that remains relatively constant across the rat's life span (Bonthius and West, 1991;Napper and West, 1995). Purkinje cell numbers, relative to untreated controls, are reduced from 20-50%, with some regional differences in the pattern of Purkinje cell depletion.…”

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

“…These include giving ethanol to the pregnant or lactating dams as a liquid diet (Pinazo-Duran et al 1993), or through an intraperitoneal injection (Ashwell & Zhang, 1994). Alternatively, pups can be given ethanol directly by gastric intubation together with a period of artificial rearing (West, 1993 ;Pauli et al 1995) or by the ethanol vapour inhalation method (Karanian et al 1986). A distinct advantage of the vapour inhalation method is that a known concentration of ethanol can be delivered easily to the pup causing a minimum of distress.…”

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

“…The tissue blocks were cut subsequently on a Historange microtome at a nominal section thickness of 6 µm until all the tissue had been exhaustively serially sectioned. A sample of 1 in 20 (f3 l 20) of these sections was chosen by a systematic random sampling procedure (Bedi et al 1992 ;Pauli et al 1995), mounted on glass slides and stained with 0n1 % cresyl violet (Drury & Wallington, 1976).…”

“…In a recent study we (Pauli et al 1995) have found that acute exposure of rats to alcohol for a period of just a few hours on PND 5 resulted in a marked deficit in Purkinje cell numbers. However, similar exposure on PND 10 had no significant effect.…”

“…The period of maximal vulnerability in the rat is therefore thought to coincide with this postnatal period. Ethanol administration to rats during early postnatal life has been shown to result in behavioural anomalies (Goodlett et al 1987 ;Kelly et al 1987 ;Meyer et al 1990 ;Pauli et al 1995) and various cerebellar deficits (Phillips & Cragg, 1982 ;Pierce et al 1989 ;Goodett et al 1990 ;Hamre & West, 1993 ;Pauli et al 1995).…”