The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory.
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.
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Elodie
E
Marciniak
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Emilie
E
Faivre
Centre de Psychiatrie et Neurosciences, UMR_S 894, Faculté de Médecine, Université Paris Descartes, 75014, Paris.
Patrick
P
Dutar
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Claire
C
Alves Pires
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Dominique
D
Demeyer
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Raphaëlle
R
Caillierez
Université de Lille, F-59000 Lille, France.|SFR DN2M, 59000 Lille France.
Charlotte
C
Laloux
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Luc
L
Buée
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
David
D
Blum
Université de Lille, F-59000 Lille, France.|Inserm UMR_S1172, Jean-Pierre Aubert Research Centre, F-59000 Lille France.|CHU-Lille, F-59000 Lille France.
Sandrine
S
Humez
D000818:Animals; D054405:Chemokine CCL3 / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D018377:Neurotransmitter Agents