title: Chemokine CCL2 modulation of neuronal excitability and synaptic transmission in rat hippocampal slices.
abstract: In addition to its well-characterized effects in immune system, chemokine CC motif ligand 2 (CCL2, formerly known as monocyte chemoattractant protein-1) is believed to play an important role in brain physiological and pathological processes. It has been shown that CCL2 and its cognate receptor chemokine CC motif receptor 2 are constitutively expressed in several brain regions including the hippocampus, and the expression is up-regulated under pathological conditions. Whereas most investigations have so far focused on its involvement in CNS pathology, few studies have examined the effects of CCL2 on neuronal and synaptic physiology. In this study, we tested the effects of CCL2 on neuronal excitability and excitatory synaptic transmission in the CA1 region of rat hippocampal slices using whole-cell patch clamp techniques. Bath application of CCL2 depolarized membrane potential and increased spike firing in CA1 neuronal cells. Bath application of CCL2 also produced an increase of excitatory post-synaptic currents recorded in Schaffer-collateral fibers to CA1 synapses. Quantal analysis revealed that CCL2 increased the frequency of spontaneous excitatory post-synaptic current occurrence and mean quantal content. Taken together, our data indicate that CCL2 enhances neuronal excitability and synaptic transmission via pre-synaptic mechanisms. These results support the emerging concept that chemokines function as neuromodulators in the CNS.
authors.affiliation: The Laboratory of Neurophysiology, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hongmei
authors.initials: H
authors.lastname: Tang
authors.forename: Jianuo
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2