Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function

Translational Psychiatry, 2021 · DOI: https://doi.org/10.1038/s41398-021-01399-3 · Published: April 19, 2021

Simple Explanation

Lithium is a common medication for mood disorders, but how it affects human brain cells is not well understood. This study looks at how different concentrations of lithium impact human neurons grown in the lab. The researchers found that lithium increased neuronal activity at all concentrations. High (overdose) concentrations caused abnormal electrical activity similar to seizures. An anti-epileptic drug, Perampanel, was able to suppress the seizure-like activity caused by high lithium concentrations, suggesting a potential treatment strategy for lithium overdose.

Study Duration

Not specified

Participants

Three in-lab produced human iPSC lines

Evidence Level

Not specified

Key Findings

1
Therapeutic concentrations of lithium increase neuronal excitability and network activity in human iPSC-derived cortical neurons.
2
Overdose concentrations of lithium induce epileptiform-like activity in human cortical neurons, resembling chemically induced seizures.
3
Perampanel, an AMPA-receptor antagonist, suppresses lithium overdose-induced epileptiform-like activity in human iPSC-cortical circuits.

Research Summary

This study investigates the acute effects of therapeutic and overdose concentrations of lithium on human iPSC-derived cortical neurons using MEA and patch-clamp techniques. The findings reveal that therapeutic lithium concentrations enhance neuronal excitability, while overdose concentrations induce epileptiform-like activity. The study demonstrates that Perampanel, an AMPA receptor antagonist, can effectively suppress the epileptiform-like activity caused by lithium overdose, suggesting a potential therapeutic intervention.

Practical Implications

Understanding Lithium's Effects

Provides insights into how lithium impacts human neuronal function at different concentrations, aiding in understanding its therapeutic and toxic effects.

Potential Treatment Strategy

Suggests Perampanel as a potential therapeutic intervention for managing lithium overdose-induced seizures.

Drug Development Platform

Establishes a human iPSC-derived neuronal model as a valuable tool for studying neuropsychological and anti-epileptic drugs.

Study Limitations

1
The study uses an in vitro model, which may not fully replicate the complexity of the human brain.
2
The long-term effects of lithium and Perampanel are not investigated.
3
The precise mechanisms underlying lithium's effects on neuronal excitability require further investigation.

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