Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: evidence for its colocalization with neurotransmitters and neuropeptides

Abstract

The monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 are key modulators of immune functions. In the nervous system, MCP-1/CCL2 is implicated in neuroinflammatory pathologies. However, cerebral functions of MCP-1/CCL2 under normal conditions are still unclear. In this study, using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific rat MCP-1 enzyme-linked immunosorbent assay (ELISA) approaches, we observed that MCP-1/CCL2 mRNA and protein were expressed in different punched regions of the normal rat central nervous system. Immunohistochemical studies further revealed that this chemokine is constitutively expressed not only in astrocytes but also in neurons, in discrete neuroanatomical regions. Neuronal expression of MCP-1/CCL2 is mainly found in the cerebral cortex, globus pallidus, hippocampus, paraventricular and supraoptic hypothalamic nuclei, lateral hypothalamus, substantia nigra, facial nuclei, motor and spinal trigeminal nuclei, and gigantocellular reticular nucleus and in Purkinje cells in the cerebellum. Moreover, we obtained the first evidence that MCP-1/CCL2 is constitutively expressed in cholinergic neurons, notably in the magnocellular preoptic and oculomotor nuclei, and in dopaminergic neurons of the substantia nigra pars compacta. In addition, in the lateral hypothalamic area, MCP-1/CCL2 co-localized with melanin-concentrating hormone-expressing neurons. Interestingly, we demonstrate a co-localization of MCP-1/CCL2 with vasopressin in magnocellular neuronal cell bodies and processes in the supraoptic and paraventricular hypothalamic nuclei, as well as in processes in the internal layer of the median eminence and in the posterior pituitary. Taken together, our data suggest that MCP-1/CCL2 could act as a modulator of neuronal activity and neuroendocrine functions.