Neuroinflammation is a feedback mechanism against infection, with recent studies 
suggesting a neuromodulatory role. The chemokine, (C-C motif) ligand 2 (CCL2), 
and its receptor, (C-C motif) receptor type 2 (CCR2), affect neuromodulation and 
migration in response to damage. Although CCL2 co-localizes with neuropeptides 
in the hypothalamus that control voluntary behavior, the function of CCL2/CCR2 
is unknown. This led us to consider the possibility that CCL2 acting through 
CCR2, under natural conditions, may affect the migration and peptide levels of 
hypothalamic neurons that control voluntary behavior. This study used primary 
embryonic hypothalamic neurons to examine the effect of CCL2 on migratory 
behavior and on levels of the peptides, enkephalin (ENK) and galanin. Treatment 
with CCL2 led to a significant, dose-dependent increase in the number of 
migrated neurons and an increase in the velocity and distance traveled. CCL2 
also significantly increased the number of ENK-expressing and CCR2/ENK 
co-expressing neurons and the percentage of neurons that contain higher levels 
of ENK. Lastly, CCL2 produced a dose-dependent increase in expression of ENK and 
galanin. These results provide evidence for a stimulatory effect of CCL2 on 
embryonic hypothalamic neurons involving changes in migratory behavior, 
expression, and synthesis of neuropeptides that function in controlling 
behavior. Our results demonstrate that the chemokine, CCL2, functions through 
its receptor, CCR2, to stimulate the migration and expression of the orexigenic 
peptides, enkephalin (ENK) and galanin (GAL), in developing embryonic 
hypothalamic neurons that are important for controlling ingestive behavior. This 
evidence reveals broad effects of CCL2 in the developing hypothalamus, showing 
this chemokine system to be tightly linked to the hypothalamic peptide neurons.