Lithium-induced neuroprotective activity in neuronal and microglial cells: A purinergic perspective.

Psychiatry Research
Carolina GubertAna Maria Oliveira Battastini

Abstract

Lithium is the mainstay of pharmacotherapy for treating bipolar disorder (BD). However, despite its wide use for over 60 years in the clinic, its mechanisms of action are not yet well defined. Elucidating lithium's mechanism of action will not only shed light on the pathophysiology of BD, but also potentially uncover new treatment targets. Previous studies suggest that the purinergic system may be involved in lithium's neuroprotective action; thus, the specific aim of this study is to better understand the neuroprotective action of lithium against ATP-induced cellular effect in both neuronal and microglial cellular lineages. We used PC12 neuronal and N9 microglial cells, evaluating cell death by cell counting and Annexin/PI cytometry assay, P2 × 7R immunocontent and ectonucleotidases activity, together with cytokine and nitrite assessment for microglial activity determination. Our results indicate that cells of different neural origins are responsive to ATP, in the sense of neuronal excitotoxicity and microglial switch into an activated M1-like phenotype respectively. Lithium, in turn, modulates the response in neuronal PC12 cells, preventing ATP-induced cell death. On the other hand, in N9 microglial cells, lithium was unable ...Continue Reading

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Feb 7, 2021·International Journal of Molecular Sciences·Kosma Sakrajda, Aleksandra Szczepankiewicz

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