S06
ROLE OF INNATE IMMUNE SYSTEM IN THE ETHANOL-INDUCED BRAIN DAMAGE, BEHAVIOURAL DYSFUNCTIONS AND ADDICTION
S06.1
BINGE DRINKING INDUCES SIGNIFICANT CHANGES IN THE INNATE IMMUNE SYSTEM

Abstract

Chronic and intermittent alcohol consumption leads to cognitive impairment in the brain due to the ethanol's action on specific neurotransmitter systems and intricate signalling pathways. Glial cells actively participate in brain function by nurturing neurons and facilitating neuronal activity as well having an immunological role to protect brain cells from invading pathogens. Dysregulation of this immune function induced by intermittent alcohol abuse may shift the homeostatic balance of inflammatory mediators to a proinflammatory state, activating microglia and inducing neuronal loss thereby inducing behavioural and cognitive impairments. Molecules, which could prevent the microglial activation and cytokine production would downregulate the pro-inflammatory state and help to prevent the decline of cognitive impairment. Studies of a ‘binge drinking’ adolescent female rats identified increased levels of glutamate in the dentate gyrus region of the hippocampus, which were associated with activated microglia. Such microglia will release glutamate when activated as well as a plethora of pro-inflammatory cytokines, e.g. IL-6 and TNFα. Oral administration of a taurine analogue, ethane-β-sultam to such ‘binge drinking’ rats for a 3-week period stabilized IKBα within the microglial cell, thereby preventing NFkappaB translocation to the nucleus and cytokine production. Activated microglia were no longer visible after immunohistochemical staining of the dentate gyrus brain region. The innate immune system, which is activated by intermittent alcohol use, can be suppressed by the use of molecules which target specific activators of this system, i.e. NFkappaB.

ERAB funding is gratefully acknowledged.