OtherMolecular autism2023

The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome.

Ricardo Martín, Alberto Samuel Suárez-Pinilla, Nuria García-Font and 7 others

PMID 37029391

WHAT IT FOUND

In mice with Fragile X syndrome, a drug activating mGluR4 receptors restored cerebellar synaptic plasticity.

This improved motor learning in skilled reaching and eyeblink conditioning, and normalized social interaction behaviors compared to untreated mice.

Key findings

01The drug VU 0155041 restored parallel fiber to Purkinje cell Long Term Potentiation (LTP) in Fragile X mice.

02Treatment improved motor learning deficits in skilled reaching and classical eyeblink conditioning tasks.

03The drug reversed deficits in sociability and social novelty behaviors.

STILL TO COME

How it was doneWhat they found

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What it does not show

This is an animal study; findings do not directly translate to human clinical practice. Systemic administration of the drug may affect many neurons and circuits across several brain regions, not just the cerebellum. The drug was administered as a single dose in most tests; the effects of chronic administration are unknown.

Declared interests

Funded by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Ciencia e Innovación, Universidad Complutense de Madrid, and Junta de Andalucía. No commercial conflicts declared.

The easy way to misread this

Do not assume this drug is ready for human use. This is a preclinical mouse study. The improvement in motor and social behaviors was seen in a genetic model of Fragile X syndrome, not in human patients, and the drug's safety and efficacy in humans have not been tested here.

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The study

Participants
Mice (exact total not specified, cohorts of 10-33 per group)
Certainty of evidence
Low

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    Cite

    Ricardo Martín, Alberto Samuel Suárez-Pinilla, Nuria García-Font, et al. The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome. Molecular autism. 2023.

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