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Impact of maternal obesity on cerebral structure and function of offspring

Supervisor: Emily Camm, Abigail Fowden

Clinical and experimental studies have demonstrated a link between obesity in pregnancy and increased risk of cardiovascular and metabolic dysfunction in offspring. In contrast, relatively few studies have determined the impact of obesity in pregnancy on cerebral structure and function in offspring. Given the increasing rates of obesity in pregnant women, we need to know much more about the effects of maternal nutrition on the brain and mental health of the offspring, and the mechanisms of developmental programming involved. Using a mouse model of maternal obesity during pregnancy, this knowledge gap will be addressed by asking four questions:

Aim 1: Does maternal obesity lead to alterations in behaviour, anxiety and cognition in offspring? Female mice will be fed a standard control chow diet or an obesogenic diet prior to mating, during pregnancy and lactation. Behaviour of offspring will be assessed early in development and with ageing (2, 6 and 12 months of age) using a battery of tasks (e.g. elevated plus maze, social interaction tests, automated touchscreen platform to assess cognitive and attentional function).

Aim 2: Does maternal obesity alter brain morphology in offspring? Brain tissue will be collected from fetuses during pregnancy and offspring at 2, 6 and 12 months of age, to assess development, synaptic morphology, neurotransmitter levels and receptors, using immunohistochemical, molecular and stereological techniques. Molecular markers of senescence will also be assessed.

Aim 3: Does maternal obesity increase oxidative stress in offspring? Lipid peroxidation, nitrosative and mitochondrial oxidative stress will be determined in the brains and plasma of fetuses during pregnancy and in offspring after birth, using Western blotting, colorimetric assays and immunohistochemistry techniques.

Aim 4: Can antioxidant supplementation ameliorate any programmed effects of maternal obesity on offspring cerebral structure and function? To determine if oxidative stress underlies the molecular basis via which maternal obesity may programme offspring behaviour and cerebral morphology, aims 1-3 will be addressed in the offspring of obese mothers who are administered antioxidants during pregnancy and lactation.

 

Relevant references

Drake AJ, Reynolds RM. Impact of maternal obesity on offspring obesity and cardiometabolic disease risk. Reproduction 2010;140:387-98.

Rivera HM, Christiansen KJ, Sullivan EL. The role of maternal obesity in the risk of neuropsychiatric disorders. Frontiers in neuroscience 2015;9:194.

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