The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory

Sci Rep. 2015 Oct 29;5:15862. doi: 10.1038/srep15862.

Abstract

Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL3 / metabolism
  • Chemokine CCL3 / pharmacology*
  • Hippocampus / metabolism*
  • Long-Term Potentiation / drug effects*
  • Long-Term Synaptic Depression / drug effects*
  • Male
  • Memory / drug effects*
  • Mice
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / pharmacology*
  • Synaptic Transmission / drug effects*

Substances

  • Ccl3 protein, mouse
  • Chemokine CCL3
  • Neurotransmitter Agents