Home » Prenatal Alcohol Exposure Causes Persistent Neuroinflammation and Age- and Sex- Specific Effects on Cognition and Metabolic Outcomes in an Alzheimer’s Disease Mouse Model

Prenatal Alcohol Exposure Causes Persistent Neuroinflammation and Age- and Sex- Specific Effects on Cognition and Metabolic Outcomes in an Alzheimer’s Disease Mouse Model

Kathleen R. Walter1, Dane K. Ricketts1, Brandon H. Presswood1, Susan M. Smith1,2 and Sandra M. Mooney1,2

1 UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis NC 28081, USA
2 Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis NC 28081, USA

Prenatal alcohol exposure (PAE) causes lasting behavioral deficits and increases risk of metabolic diseases including obesity and glucose intolerance. Alzheimer’s Disease (AD) is a neurodegenerative disease associated with dementia; the risk for this is higher in adults with metabolic diseases. We use an established mouse model of AD to test whether PAE exacerbates the AD-related cognitive decline, and that this associates with metabolic impairment and neuroinflammation. Pregnant 3xTg-AD mice (presenilin/amyloid precursor protein/tau) that display AD-like behaviors, received 3g/kg alcohol (ALC) from embryonic day 8.5 through 17.5. We evaluated recognition memory and associative memory (fear conditioning) in 8-10 male and female offspring per group at 3 months of age (mo), 7mo, and 11mo, and assessed glucose tolerance, body composition, and hippocampal microglial activation at 12mo. ALC females had higher body weights than controls beginning at 5mo. Controls showed improved recognition memory at 11mo; this was not seen in ALC mice. Older animals froze more during fear conditioning than younger, and ALC mice were hyper-responsive to the cue. Fasting blood glucose was lower in ALC males and higher in ALC females than controls. Glucose values and adiposity negatively correlated with behavior in an exposure- and sex-dependent manner, i.e., in ALC females. At 12mo, hippocampal microglial activation was higher in ALC than controls and this showed a trend to correlate with recognition memory. Overall, ALC animals showed age-related cognitive impairments that did not appear to interact with AD risk, but did correlate with their metabolic dysfunction.