Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines.
Ryohei Takada, Michihiro Toritsuka, Takahira Yamauchi and 12 others
PMID 38383466WHAT IT FOUND
Macrophages from people with autism shortened neuron dendrites more than those from controls.
This damage was caused by secreted inflammatory cytokines. Blocking these cytokines in the lab prevented the shortening.
Key findings
01Neurons co-cultured with macrophages from individuals with autism showed significantly shorter dendrites and fewer branches than those co-cultured with macrophages from typically developed individuals.
02The dendritic shortening was caused by secreted factors rather than physical contact, as it occurred even when macrophages were separated from neurons by a membrane.
03Adding neutralizing antibodies against TNF-alpha and IL-1-alpha prevented the dendritic shortening induced by these macrophages.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study used a very small sample size of only 10 participants. All participants were male, so results may not apply to females. The neurons were derived from healthy control cell lines, not from the participants themselves, so the specific interaction between ASD neurons and ASD macrophages was not tested. The cell culture model lacked astrocytes and inhibitory neurons, which are present in the real brain. Macrophages were artificially polarized in the lab, which may not reflect their state in the body.
Declared interests
The authors declared no competing interests.
The easy way to misread this
Do not interpret this as evidence that blocking TNF-alpha or IL-1-alpha is a treatment for autism. This was a small laboratory study using cells in a dish. It shows a mechanism in isolation, not a clinical outcome in humans.