OtherMolecular autism2023

Tau reduction attenuates autism-like features in Fmr1 knockout mice.

Shanshan Zhao, Xiangyu Jiang, Linkun Han and 7 others

PMID 37936174

WHAT IT FOUND

In male Fragile X mice, lowering tau improved autism-like social and repetitive behaviors, nest building, and dendritic spine changes.

No human therapy was tested.

Key findings

01Tau protein and Mapt mRNA were higher in the cortex, but not the hippocampus, of Fmr1 knockout mice.

02Genetic reduction of tau in Fmr1 knockout mice improved nest building, reduced increased self-grooming time, and restored social preference and social novelty.

03Tau-targeting antisense oligonucleotide treatment reduced self-grooming time, improved nest building, and improved social preference and social novelty in Fmr1 knockout mice.

STILL TO COME

How it was doneWhat they found

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What it does not show

Only male mice were tested, and the authors say female effects need further study. The authors did not know whether tau antisense treatment gives a partial or complete rescue. The authors did not know whether P38/MAPK signaling is the responsible mechanism. The study tested mice, not people.

Declared interests

The funding statement names the National Natural Science Foundation of China.

The easy way to misread this

Do not read the mouse rescue as evidence that tau lowering is a proven therapy for people with Fragile X or autism. The study tested male mice and did not report human outcomes.

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The study

Participants
Male mice. Behavioral genotype groups: WT n = 11, Mapt ± n = 11, Fmr1 −/y n = 9, Fmr1 −/y ; Mapt ± n = 10. ASO behavioral groups: ASO-NC n = 10, ASO-Tau n = 11.
Certainty of evidence
Low

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    Cite

    Shanshan Zhao, Xiangyu Jiang, Linkun Han, et al. Tau reduction attenuates autism-like features in Fmr1 knockout mice. Molecular autism. 2023.

    Read the original