Correlation of axon size and myelin occupancy in rats prenatally exposed to methamphetamine

The abuse of methamphetamine (MA) and other psychostimulants is a social and medical problem. In particular, the use of these drugs by pregnant women results in an increased number of children exposed prenatally to psychostimulants. Our previous work has demonstrated that prenatal exposure to MA affects the normal development of the rat visual system due to alterations of biochemical mechanisms and oxidative stress. It was also demonstrated that prenatal exposure to MA affects the dopaminergic system of the rat retina and optic nerve (ON) myelination. The present work was conducted to evaluate the effects of prenatal exposure to MA on the development of the ON in terms of axon growth and the myelin sheath. Pregnant female rats were given 5 mg/kg/day MA, subcutaneously (s.c.), in 0.9% saline from gestational day (GD) 8 to 22. The pair-fed control group was injected s.c. with an isovolumetric dose of 0.9% saline. Qualitative analysis was performed using representative electron ultramicrographs. Quantitative analysis was performed at an electron microscopic level on ON cross sections; parameters measured included myelinated/unmyelinated ratio, outer axon mean area, inner axon mean area, myelin mean area, myelin occupancy and distribution of axons by size. The ON of prenatally MA-exposed rats presented a higher rate of deformed axons and slighter lamellar separation. At PND 21, the average outer axon area of MA-treated males was significantly reduced. The average inner axon area only showed a significant difference between MA and control males for axons with an area of less than 0.3 µm2. The average myelin area of MA-treated males was significantly reduced, and in MA-treated females was only significantly reduced in axons with an area of less than 0.3 µm2. The percentage of myelin occupancy was significantly affected in MA-treated males, and in MA-treated females in the group of axons with an area of more than 0.3 µm2. At PND 14 no significant differences were found between MA and control groups. The spectrum of ON myelinated axon size of MA-treated animals was shifted to the left at PND 14 and PND 21 for both genders. These results are in agreement with previous animal studies of prenatal and perinatal exposure to drugs of abuse. Taken together, these data indicate that the ON is vulnerable to early exposure to MA which causes developmental changes and may interfere with the functioning of the visual system.