HOT BABY: HOW EARLY LIFE INFLAMMATION PROGRAMS THE BRAIN

Quentin J. Pittman, Hotchkiss Brain Institute and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada

Babies often get sick during the first few months of their life, but we do not know if this experience within an early developmental window has long term effects on adult brain and behavior. As rodents in most of our animal colonies are raised under condition where sickness is virtually absent, this provides an opportunity to explore this question. By giving a low, non-toxic dose of lipopolysaccharide (i.p. LPS- a component of gram negative cells walls) we are able to cause a controlled inflammation mimicking a bacterial infection. While the effects of the inflammation are transient, and resemble that seen in much older animals, there are long lasting changes in behavior and neuronal properties seen only if the inflammation is given during early life. Changes to behavior that persist into adolescence and adulthood include sexually dimorphic alterations in conditioned fear extinction, adolescent social interactions and anxiety like behaviors. Even as adults, brain are more excitable, with increased susceptibility to convulsants and more prevalent EEG symptoms in models of epilepsy. Responses to second stressors may also be affected. Mechanistic  changes that have been associated with early life inflammation include long term alterations in endocannabinoid signaling, expression of various neurotransmitters and their receptors and altered, sexually dimorphic electrophysiological properties of hippocampal neurons. It is well known that the adult brain is a product not only of our genes but also of early life experience; early life inflammation can now be recognized as one of the factors that affect brain development.