Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity

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Hridi, Shehla U. and Franssen, Aimée J.P.M. and Jiang, Hui-Rong and Bushell, Trevor J. (2019) Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity. Molecular and Cellular Neuroscience, 95. pp. 71-78. ISSN 1044-7431 (https://doi.org/10.1016/j.mcn.2019.01.002)

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Abstract

Interleukin 16 (IL-16) is a cytokine that is primarily associated with CD4+ T cell function, but also exists as a multi-domain PDZ protein expressed within cerebellar and hippocampal neurons. We have previously shown that lymphocyte-derived IL-16 is neuroprotective against excitotoxicity, but evidence of how it affects neuronal function is limited. Here, we have investigated whether IL-16 modulates neuronal excitability and synaptic activity in mouse primary hippocampal cultures. Application of recombinant IL-16 impairs both glutamate-induced increases in intracellular Ca2+ and sEPSC frequency and amplitude in a CD4- and CD9-independent manner. We examined the mechanisms underlying these effects, with rIL-16 reducing GluA1 S831 phosphorylation and inhibiting Na+ channel function. Taken together, these data suggest that IL-16 reduces neuronal excitability and synaptic activity via multiple mechanisms and adds further evidence that alternative receptors may exist for IL-16.

ORCID iDs

Hridi, Shehla U. ORCID logoORCID: https://orcid.org/0000-0001-7906-6763, Franssen, Aimée J.P.M. ORCID logoORCID: https://orcid.org/0000-0001-6399-1663, Jiang, Hui-Rong and Bushell, Trevor J. ORCID logoORCID: https://orcid.org/0000-0003-4145-9670;
CORE (COnnecting REpositories)