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

Abstract

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged " 171 mg\dl and in the ETHD animals " 430 mg\dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection of ketamine and xylazine, and killed by intracardiac perfusion with phosphatebuffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of " 145 000-165 000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75 000 optic nerve axons (P 0n05) of which about 2n8 % were myelinated. By 30 d of age there was a total of between 75 000-90 000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P 0n001) in the ETHD animals (" 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats

“…Evidence for the effects of alcohol on the developing visual system has emerged from studies demonstrating that perinatal alcohol exposure causes hypoplasia and decreased myelination of optic nerve axons (Harris et al, 2000;Pinazo-Duran et al, 1997). In addition, recent findings indicate that neonatal alcohol administration induces apoptotic neurodegeneration of both retinal ganglion cells and neurons in brain regions receiving visual system projections such as the lateral geniculate nucleus (Tenkova et al, 2003).…”

Effectiveness of iron repletion in the diet for the optic nerve development of anaemic rats

“…Although there are not sufficient data to explain this result, the oedema in the axons and its myelin shields can be the support to clear this finding. Harris et al 29 showed that the proportion of axons that were myelinated at PND 30 was also lower in the high dose ethanol-treated animals than in the other groups. Melo et al 31 showed that the percentage of myelinated axons in the ON did not differ between methamphetamine-treated animals and their respective age-matched controls.…”

“…33,52,54 The exposure to a relatively high dose of ethanol for a short period during the rats' early postnatal life markedly influenced the development, myelination, and total numbers of ON axons. 29 In this work, we evaluated the structural impairment of the rat ON resulting from postnatal iron-deficient diet (4 mg Fe/kg diet) and the effect of iron repletion (35 mg Fe/kg diet) after weaning. The experimental design effectively produced maternal iron-deficient anaemia, which indicated low iron status of their offspring.…”

“…11,12 Trace elements deficiency, undernourishment, and exposure to drugs of abuse or alcohol induced ultrastructural changes in the ON, cornea, and retina. 25,26,29,[31][32][33][34][35][42][43][44][45][46][47][48][49][50][51][52][53] Figure 2 Mean density (a) and total number (b) of myelinated and unmyelinated fibres of the optic nerve in the control, anaemic, and recovered rats at postnatal day 32. Values are means ± SE for n ¼ 6; *Po0.05.…”

“…27,28 The visual pathways are vulnerable structures to insults such as deficiency diet, drugs of abuse, and alcohol. [29][30][31][32][33][34][35][36][37] In this study, we examined the effect of iron repletion administrated after weaning on the ON development of rats fed with an iron-deficient diet since birth until the postnatal day (PND 21). The quantitative changes analysed in the ON of iron-deficient rats and after iron repletion provides a baseline pattern to the ON damage, which will lead to a better understanding of the ophthalmologic alterations found in children breastfed from anaemic women.…”