Wednesday, 10 April 2013

Researchers discover that TGF-β inhibition improves neural production

Recently, a team of researchers from INSERM* and CEA** released a study in which they discovered, in a mouse model, that the pharmacological inhibition of the transforming growth factor beta (TGF-β) improves the production of new neurons. These findings, could help alleviate cognitive decline in elder people and treat cerebral lesions caused by radiation therapy.

In their paper, the researchers first explain that new neurons are formed throughout our life by neural stem cells and this is why our cognitive abilities stay the same. They continue saying ageing and cranial radiotherapy seem to halt this process, causing a progressive cognitive decline, which is currently untreatable. Previous studies indicate that neural stem cells survive both heavy radiation and ageing, however for some reason they stop "working correctly".

In this study, the research team hypothesised that alterations in the microenviroment where neural stem cells live are responsible for the aforementioned neurogenetic decline.

Image showing the structure of a typical neuron
Structure of a typical neuron

The researchers then experimented on mice that were given a total radiation dose of 15 Gy, divided into three equal doses of 5 Gy. The researchers report two important findings.

First, they say that the experiments showed their initial hypothesis stood correct, as the cognitive decline is attributed to alterations in the stem cell microenvironment rather than to a direct effect on the neural stem cells. Secondly, they found that they could restore neuron production in elder or irradiated mice by pharmacologically blockading the TGF-β signalling.

“Our study concluded that although neurogenesis reduced in ageing and after a high dose of radiation, many stem cells survive for several months, retaining their ‘stem’ characteristics”, says Marc-Andre Mouthon, one of the study's chief authors

The researchers believe that these findings may encourage the creation of new TGFβ-blocking therapies that will restore cognitive abilities in elder people and patients with brain lesions caused by radiotherapy.

* Institut national de la santé et de la recherche médicale (Website)
** CEA is a French government-funded technological research organisation (Website)

Pineda JR, Daynac M, Chicheportiche A, Cebrian-Silla A, Sii Felice K, Garcia-Verdugo JM, Boussin FD, & Mouthon MA (2013). Vascular-derived TGF-β increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain. EMBO molecular medicine, 5 (4), 548-62 PMID: 23526803

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