Alcohol exposure during the first two trimesters-equivalent alters the development of corpus callosum projection neurons in the rat

Abstract

Children exposed prenatally to alcohol can display a variety of neural deficits, including an altered development of the corpus callosum (CC), the largest interhemispheric axon pathway in the brain. Furthermore, these children show functional abnormalities that are related to brain regions with significant numbers of CC connections. Little is known about how alcohol imparts influence on CC development, but one possible mechanism is by affecting the corpus callosum projection neurons (CCpn) directly. The purpose of this study was to quantify the effects of prenatal alcohol exposure on the number, size and distribution of CCpn within the visual cortex. The visual cortex was selected specifically due to the many vision-related deficits noted in fetal alcohol exposed children and because the critical role of the CC in visual cortex development is well documented. Sprague-Dawley rat pups received one of four alcohol dosages during gestational days (G) 1-20, or reared as nutritional or untreated control animals. Each litter was categorized according to the peak blood alcohol concentration (BAC) experienced. Pups were removed from each litter on days equivalent to G29, G36, G43, and G50, for histology and measurement. Callosal axons were labelled retrogradely to their CCpn using DiI and the CCpn were then examined using confocal laser scanning microscopy. Differences between alcohol-exposed and control animals were observed in CCpn cell body size, number, and location with the cortex. This was particularly true of animals exposed to high doses of alcohol. In addition, some trends of CCpn development were found to be unchanged as a result of prenatal alcohol exposure. The results demonstrate clear differences in the development of CCpn in the visual cortex between alcohol-exposed and control animals and suggest that this development is particularly affected in those animals exposed to high doses of alcohol.

The Impact of Prenatal Ethanol Exposure on Neuroanatomical and Behavioral Development in Mice

“…Midline callosal hypoplasia was detected in both P0 and P20 PrEE mice, consistent with previous studies in both human and mouse that demonstrate an association between PrEE and shape abnormalities with volumetric changes in the CC (Gautam et al., ; Livy and Elberger, ). Our results show an initial thinning of the CC at birth, lasting through P20, due to PrEE.…”

“…Other studies have identified noncortical damage to the developing nervous system from PrEE. For example, West and colleagues described abnormal development in the hippocampus, cerebellum, and CC following PrEE in a rat model of FASD (Livy and Elberger, ; Livy et al., ; Maier and West, ).…”

White matter microstructure from nonparametric axon diameter distribution mapping

“…Conventional neuroanatomical methods applied to postmortem human or animal tissue have provided evidence that the ADD changes in neurological conditions such as amyotrophic lateral sclerosis (ALS) (Cluskey and Ramsden, 2001) and multiple sclerosis (MS) (Trapp et al, 1998; Evangelou et al, 2001; Lovas et al, 2000). In addition, several pathologies, including autism (Hughes, 2007), dyslexia (Njiokiktjien et al, 1994), schizophrenia (Randall, 1983), and even alcoholism (Livy and Elberger, 2008), have been associated with changes in the distribution of axon size. Changes in the number of axons and their diameters also take place throughout normal development accompanying the period of dynamic behavioral, cognitive, and emotional changes in childhood and adolescence (Yakovlev, 1967; Pfefferbaum et al, 1994; Gregg et al, 2007; Barnea-Goraly et al, 2005; Schlaug et al, 2009).…”

Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons

“…Studies conducted primarily in rodent have reported ethanol-induced impairments in neurogenesis (Goodlett and Horn, 2001), neuronal migration (Aronne et al, 2011) and axonal outgrowth (Granato et al, 2003; Lindsley et al, 2003; Livy and Elberger, 2008). Regarding the latter, low (12.5 mM) concentrations of ethanol impair growth cone responses to guidance cues, including semaphorins and netrins (Sepulveda et al, 2011), known to regulate axonal growth and targeting (Behar et al, 1996; Luo et al, 1995; Serafini et al, 1994; Steup et al, 2000).…”