CCR5 is a Suppressor for Cortical Plasticity and Hippocampal Learning and Memory
Authors
Affiliations
Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.
Biosafety and mental health: Virus induced cognitive decline.
Du C, Li G, Han G Biosaf Health. 2025; 5(3):159-167.
PMID: 40078510 PMC: 11895046. DOI: 10.1016/j.bsheal.2023.04.002.
Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.
Simons C, Kim S, Hahn Y, Boake-Agyei A, Nass S, Vo P ASN Neuro. 2025; 17(1):2447338.
PMID: 39805095 PMC: 11877617. DOI: 10.1080/17590914.2024.2447338.
IL-1ra and CCL5, but not IL-10, are promising targets for treating SMA astrocyte-driven pathology.
Allison R, Mangione C, Suneja M, Gawrys J, Melvin B, Belous N Mol Ther. 2024; 33(2):734-751.
PMID: 39673131 PMC: 11853362. DOI: 10.1016/j.ymthe.2024.12.016.
Activity-dependent transcriptional programs in memory regulate motor recovery after stroke.
Joy M, Carmichael S Commun Biol. 2024; 7(1):1048.
PMID: 39183218 PMC: 11345429. DOI: 10.1038/s42003-024-06723-3.
Qi Z, Peng J, Wang H, Wang L, Su Y, Ding L CNS Neurosci Ther. 2024; 30(8):e14924.
PMID: 39143678 PMC: 11324532. DOI: 10.1111/cns.14924.