Muramyl-dipeptide, a macrophage-derived cytokine, alters neuronal activity in hypothalamus and hippocampus but not in the dorsal raphe/periaqueductal gray of rats

Muramyl-dipeptide (MDP) is derived in vivo by degradation of bacteria cell walls and is the minimun fragments that stimulates the acute phase response to bacterial infection. The present study investigates whether this specific product of an immune response affects central nervous system (CNS) function. To this end, the activity of single neurons within the hypothalamus, hippocampus, and dorsal raphe/periaqueductal gray region prior to and following systemic (i.p.) injections was studied. The results obatined from a total of 120 cells demonstrate that single hypothalamic and hippocampal neurons, sites previously shown to aid in the integration of various environmental stimuli into physiologic processes, alter their neuronal activity in site-specific manners following MDP administration. The specificity of the responses included both the threshold for activation of particular sites, effects of increasing dosages upon response pattern characteristic, and time course to the changes observed. These resultsp therefore suggest that MDPs may play a role in the neuro-immunologic regulatory pathways during the immune response to bacterial infection.