Background: Intrauterine growth restriction (IUGR) delays oligodendrocyte development and reduces perinatal myelination. Although a risk factor for adult neurological disorders, it is unknown whether IUGR-induced myelin deficits increase vulnerability to Multiple Sclerosis. This study aimed to determine whether IUGR influences functional recovery following cuprizone-induced demyelination and subsequent remyelination.
Methods: On day 18 of pregnancy (term=22 days), rats underwent bilateral uterine vessel ligation (n=4) or sham surgery (n=4) to generate IUGR (n=12) or sham (n=13) pups. On postnatal day (P) 85, rats were randomly allocated to cuprizone (sham n=7; IUGR n=7) or regular chow feed (sham n=6; IUGR n=5) for 5 weeks (demyelination). On P118-119, motor function (grid walk, tapered beam test) and behaviour (open field) was assessed. All rats then resumed normal feed for 2 weeks to allow for remyelination. Behavioural and motor tests were performed on P132-133. Data were analysed by repeated measures ANOVA.
Results: IUGR or cuprizone had no effect on foot faults during demyelination. However, sham+cuprizone animals had significantly more foot faults during remyelination than their regular chow counterparts (p=0.018), whereas no differences were seen between the IUGR groups. Animals fed cuprizone, irrespective of sham or IUGR status, travelled further in the open field test compared to chow-fed animals in both the demyelination (p=0.042) and remyelination (p=0.048) phases. There were no differences between groups in time spent in the inner zone of the open field or on the tapered beam test.
Conclusion: Cuprizone exposure of both IUGR and sham IUGR rats resulted in a hyperactive phenotype and affected fine motor control in sham rats during remyelination, but not in IUGR rats. These results indicate that IUGR does not increase vulnerability to subsequent demyelination events in later life and suggest that IUGR may confer protection during remyelination. Further assessment of myelin status is required to confirm these conclusions.