Impaired spatial memory in mice lacking CD3ΞΆ is associated with altered NMDA and AMPA receptors signaling independent of T-Cell deficiency
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2013-11
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en
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Society for Neuroscience
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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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https://www.jneurosci.org/content/rights-permissions
Resumen
The immunoreceptor-associated protein CD3ΞΆ is known for its role in immunity and has also been implicated in neuronal development and synaptic plasticity. However, the mechanism by which CD3ΞΆ regulates synaptic transmission remains unclear. In this study, we showed that mice lacking CD3ΞΆ exhibited defects in spatial learning and memory as examined by the Barnes maze and object location memory tasks. Given that peripheral T cells have been shown to support cognitive functions and neural plasticity, we generated CD3ΞΆ-/- mice in which the peripheral T cells were repopulated to a normal level by syngeneic bone marrow transplantation. Using this approach, we showed that T-cell replenishment in CD3ΞΆ-/- mice did not restore spatial memory defects, suggesting that the cognitive deficits in CD3ΞΆ-/- mice were most likely mediated through a T-cell-independent mechanism. In support of this idea, we showed that CD3ΞΆ proteins were localized to glutamatergic postsynaptic sites, where they interacted with the NMDAR subunit GluN2A. Loss of CD3ΞΆ in brain decreased GluN2A-PSD95 association and GluN2A synaptic localization. This effect was accompanied by a reduced interaction of GluN2A with the key NMDAR downstream signaling protein calcium/calmodulin-dependent protein kinase II (CaMKII). Using the glycine-induced, NMDA-dependent form of chemical long-term potentiation (LTP) in cultured cortical neurons, we showed that CD3ΞΆ was required for activity-dependent CaMKII autophosphorylation and for the synaptic recruitment of the AMPAR subunit GluA1. Together, these results support the model that the procognitive function of CD3ΞΆ may be mediated through its involvement in the NMDAR downstream signaling pathway leading to CaMKII-dependent LTP induction.
Notas
IndexaciΓ³n: Scopus.
IndexaciΓ³n: Scopus.
IndexaciΓ³n: Scopus.
Palabras clave
Major Histocompatibility Complex, Interferon-Ξ, AMPA receptor, calcium calmodulin dependent protein kinase II, CD3 antigen, cd3 epsilon, Bone Marrow Transplantation, Gene Expression Regulation, Embryo, Mammalian
CitaciΓ³n
Journal of Neuroscience, Volume 33, Issue 47, Pages 18672 - 18685, 2013
DOI
10.1523/JNEUROSCI.3028-13.2013