The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory
Open accessAbstract
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.
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Both CXCL10 and CCL3 were shown to impair synaptic functions.
“Moreover, both cytokines were shown to impair synaptic functions (58, 59).”
From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [59]
Both CXCL10 and CCL3 have been shown to impair LTP and synaptic function.
“Both CXCL10 and CCL3 have been shown to impair LTP and synaptic function (61, 62).”
From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [62]
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- Authors
- Marciniak, E., Faivre, E., Dutar, P., Alves Pires, C., Demeyer, D., Caillierez, R., Laloux, C., Buée, L., Blum, D., & Humez, S.
- Affiliations
- Inserm (FR)
- Université Paris Descartes (FR)
- Université de Lille (FR)
- Corresponding author
- Blum, David
- Humez, Sandrine
- Venue
- Scientific Reports
- Published
- 2015-10-29
- Volume
- 5
- Issue
- 1
- Pages
- 15862-15862
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4625372
- OpenAlex
- W1887402735
- Cited by
- 148
- References
- 60
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 21 · 2023: 19 · 2022: 18 · 2021: 19 · 2020: 9 · 2019: 11 · 2018: 13 · 2017: 7 · 2016: 5 · 2015: 1
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
- Université de Lille
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- chemokines, hippocampus, synaptic transmission, synaptic plasticity, long-term potentiation, long-term depression, spatial memory, learning, CCR5 coreceptor, maraviroc, Schaffer collateral-CA1 synapses, intracerebroventricular administration
- MeSH terms
- Animals, Hippocampus, Male, Memory, Synaptic Transmission, Long-Term Potentiation, Neurotransmitter Agents, Long-Term Synaptic Depression, Mice, Chemokine CCL3
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