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

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

Marciniak E1,2,3, Faivre E1,2,3, Dutar P4, Alves Pires C1,2,3, Demeyer D1,2,3, Caillierez R1,2,3, Laloux C1,5, Buée L1,2,3, Blum D1,2,3, Humez S1,2,3.

Author information

1
Université de Lille, F-59000 Lille, France.
2
Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.
3
CHU-Lille, F-59000 Lille France.
4
Centre de Psychiatrie et Neurosciences, UMR_S 894, Faculté de Médecine, Université Paris Descartes, 75014, Paris.
5
SFR DN2M, 59000 Lille France.

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.

PMID:
26511387
PMCID:
PMC4625372
DOI:
10.1038/srep15862
[Indexed for MEDLINE]
Free PMC Article

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