Title : Low dose chronic prenatal alcohol exposure abolishes the pro-cognitive effects of angiotensin IV
Foetal alcohol syndrome (FAS) is a condition that currently affects approximately 1% of babies born in Europe and North America. It is characterised by memory impairment, developmental delay and distinctive facial features. This research uses a Mouse Prenatal Alcohol Exposure (PAE) model to explore the effects of PAE on learning, memory and to explore the potentially beneficial effects of common drugs previously shown to have cognitive enhancing effects in both humans and animals. 60 mice (M=30 F=30) C57 Breeding harem of mice, were exposed to 5% ethanol throughout pregnancy. After weaning, the offspring received Losartan (10mg/kg) via their drinking water for eight weeks. At three months of age, learning and memory was assessed using the novel object recognition paradigm. The results indicate that PAE caused a significant decrease in offspring body weight. Treatment with Losartan caused no growth impairment or renal damage. Novel object recognition indicated that PAE caused male offspring to spend significantly less time exploring the novel object than controls and that treatment with Losartan had the effect of improving awareness of the novel object both in the control and alcohol group; in addition to decreasing anxiety (p≤0.05). A significant opposite effect was noticed in the female alcohol progeny when compared to the male alcohol progeny (p≤0.05). Losartan in female alcohol progeny had no effect on anxiety. Overall, male control losartan spent more time exploring the novel object than male alcohol losartan (p≤0.05). The results suggest that Losartan had no deleterious effects on the development of the animals, and was able to improve learning and memory in control animals without effect in PAE mice.
Audience take away:
• Our mouse paper demonstrates that low-level, but chronic, alcohol intake during pregnancy has an effect on learning and memory without there being any obvious physical effects (e.g birth weight, gross anatomical changes).
• Importantly the study suggests that there are sex differences, which might reflect differences in rate of development, or some people suggest that oestrogens are protective. (This is illogical though because both male and female foetus is exposed to maternal oestrogens, more likely that androgens are deleterious).
• How might this change practice? It reinforces the message about no safe limit of alcohol. • Our original hypothesis was that losartan may improve cognition in young children, as it does in adults. The mouse results suggests that this will not be the case.