European Journal of Inflammation (Sep 2012)

The Inflammatory Chemokine CXCL10 Modulates Synaptic Plasticity and Neuronal Activity in the Hippocampus

  • J.N. Kodangattil,
  • G. Möddel,
  • M. Müller,
  • W. Weber,
  • A. Gorji

DOI
https://doi.org/10.1177/1721727X1201000307
Journal volume & issue
Vol. 10

Abstract

Read online

Chemokines, a family member of cytokines, have been shown to play a major role in central nervous system inflammation. Among other chemokines, CXCR3 and its ligand CXCL10 are involved in the pathophysiology of several neuroinflammatory conditions. Most of these conditions are also associated with an increased incidence of seizure or epilepsy. Using age-matched wild-type (WT), as well as CXCR3-receptor-deficient (CXCR3-KO) mice, the present study aimed to investigate the effect of the chemokine CXCL10 and its receptor CXCR3 on synaptic plasticity as well as neuronal activities in hippocampal brain slices. Using field potential and intracellular recordings, the effect of exogenous CXCL10 on tetanus-induced long-term potentiation (LTP) as well as the neuronal spike activity was evaluated in hippocampal CA1 area. Exogenous application of CXCL10 enhanced LTP in WT mice, whereas it exerted no significant effect on CXCR3-KO mice. During intracellular recordings of spontaneous spike activity, exogenous application of CXCL10 significantly enhanced the amplitude, duration, and after-hyperpolarization of action potentials in slices obtained from WT mice compared to CXCR3-KO mice. In addition, CXCR3-KO mice exhibited a lower GABA A -mediated excitation in hippocampal CA1 neurons compared to WT mice. These data show that the inflammatory chemokine CXCL10, probably via its receptor CXCR3, modulates neuronal activity and synaptic plasticity in the hippocampus. CXCL10 may be involved in seizures observed during neuroinflammatory diseases such as meningitis and encephalitis.