OtherMolecular autism2019

Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity.

Tetsuya Tatsukawa, Matthieu Raveau, Ikuo Ogiwara and 7 others

PMID 30962870

WHAT IT FOUND

Mice with reduced function of a sodium-channel gene were hyperactive, showed mixed signs of anxiety-like behavior, and had impaired fear-memory extinction.

A drug that boosts AMPA receptors reduced their hyperactivity. This is mouse work, not evidence for human therapy.

Key findings

01Scn2a KO/+ mice showed novelty-induced hyperactivity and reduced anxiety-like behavior in open-field and elevated-plus-maze tests.

02CX516 reduced traveled distance and rearing in Scn2a KO/+ mice but did not significantly change anxiety-like measures such as time in the open-field center.

03Scn2a KO/+ mice showed stronger fear-conditioning retention, impaired fear extinction, and increased gamma-band activity in the medial prefrontal cortex.

STILL TO COME

How it was doneWhat they found

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What it does not show

This is a mouse model study, not a clinical trial, so it does not show what therapists should do with patients. Only male mice were tested, so it says nothing about females. Several outcomes were inconsistent across tasks, especially anxiety and depression-like behavior. The drug was tested acutely in mouse behavior, not in people, and safety, dosing, and long-term effects are not addressed. The paper reports many separate behavioral tests in different mouse cohorts, so the overall picture is descriptive rather than a single clinical outcome.

Declared interests

The supplied text lists funding from the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, and the National Institute of General Medical Sciences. It does not provide an author conflict-of-interest statement.

The easy way to misread this

Do not read the drug's effect in mice as evidence that a similar drug should be used for human patients. The study was done in mice, did not test clinical therapy, and did not address safety or long-term outcomes.

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The study

Participants
Adult male mice only; cohort sizes varied by experiment and no single total participant count is given.
Certainty of evidence
Low

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    Tetsuya Tatsukawa, Matthieu Raveau, Ikuo Ogiwara, et al. Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity. Molecular autism. 2019.

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