Prenatal Ethanol Exposure Reduces Spinal Cord Motoneuron Number in the Fetal Rat but Does Not Affect GDNF Target Tissue Protein

Abstract

Fetal rats were exposed throughout gestation to one of three diets: an ethanol-containing liquid diet, a liquid diet with the isocaloric substitution of sucrose for ethanol or a laboratory chow control diet. At postnatal day 1 (P1), the spinal cords were taken for analyses of motoneuron number and size. These analyses revealed a significant loss of motoneurons and a reduction of motoneuron size in the ethanol-exposed animals, compared to both sucrose and chow controls. Spinal cord length and ventral horn volume were not altered as a result of ethanol treatment, so the change in motoneuron number cannot be attributed to volumetric changes. The content of the motoneuron survival factor glial cell-line-derived neurotrophic factor (GDNF) was also assessed in the P1 limb motoneuron target tissue. This analysis was undertaken because GDNF is a potent survival factor for developing motoneurons and has been shown to protect this population from ethanol neurotoxicity. Thus, its depletion could contribute to motoneuron loss. These analyses, using the ELISA assay, did not detect reductions in GDNF in the ethanol-exposed animals. Therefore, alterations in other neurotrophic factors or ethanol neurotoxicity by other means appear to be responsible for the motoneuron loss. These results are consistent with earlier studies in the chick embryo, which also found reduced motoneuron numbers as a function of developmental ethanol exposure, and point again to the general lethality of ethanol to the developing nervous system.

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

“…However, several studies suggest different sensitiveness to ethanol of cranial and spinal motoneurons [36], [37], [38]. Using other animal models, some authors have shown that ethanol exposure during gestation causes a significant loss of motoneurons and a reduction of motoneuron diameter [39]. Different windows of exposure and doses might explain the discrepancy between our results and those mentioned before.…”

Prenatal exposure to drugs: effects on brain development and implications for policy and education

“…Exposure during all gestational periods has dramatic teratogenic consequences 131-133. There are reports of a decrease in spinal and cranial motor neuron production and size, neocortical and hippocampal dysgenesis, increased neuronal cell death, reduced or delayed neuronal migration and a decrease in myelination 134-137. Ethanol exposure also disrupts the integrity of plasma membrane receptors 138, 139.…”

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

“…Some examples of neurological dysfunction and developmental disturbances include reductions in spinal and cranial motor neuron production and size (Barrow Heaton et al 1999); disturbance of neurogenesis and/or gliogenesis in the neocortex (Miller and Robertson 1993), cerebellum (Shetty and Phillips 1992), and hippocampus (Redila et al 2006); increased neuronal cell death (Olney et al 2000); abnormal neuronal migration and decreased myelination (Ozer et al 2000); disruptions in the integrity of plasma membrane NMDA receptors (Honse et al 2003; Hughes et al 2001); adverse effects on the endocrine and immune system (Zhang et al 2005; Wilcoxon et al 2005); and dysregulation of the hypothamic-pituitary-adrenal (HPA) axis (Glavas et al 2007), which can lead to increased responsiveness to later stressors and reduced plasticity in the hippocampus (Sliwowska et al 2010). …”