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Scientific result | European ＆ international partnerships | Brain | Neurodegenerative diseases
An international team involving the CEA-I2BM has just demonstrated that astrocytes induce the neuronal metabolism abnormalities that are characteristic of Huntington’s disease.
Huntington’s disease, which affects 8,000 people in France, is a hereditary neurodegenerative disease caused by the mutation of the protein huntingtin. Incurable at this time, the disease manifests itself in adulthood through involuntary movements, behavioral disorders and cognitive deficits. The disease can lead to death 10-15 years after the onset of symptoms. Even before these first manifestations, cerebral glucose consumption is reduced in carriers of the mutation, as revealed by PET imaging1.
A team from the I2BM, in collaboration with French, American and Chilean2 laboratories, has explored the mechanisms of this metabolic alteration in rodent carriers of the mutated human huntingtin gene. Using an imaging technique equivalent to monitoring by PET, the researchers observed the same abnormalities in glucose consumption, in the same brain regions in mutant rodents as in human patients. Next, they examined neurons in vitro but also astrocytes3, which have not been well-studied in this respect to date. Their results show that grown in isolation, neurons as well as mutated astrocytes have a normal metabolism. In contrast, neurons (mutated or not) consume less glucose than normal when they are co-cultured with mutated astrocytes. The latter are therefore responsible for the metabolic alteration of neurons, presumably by an oxidative stress mechanism. The team is continuing its research with other animal models, with one of their goals being to develop new methods for monitoring cerebral glucose metabolism in patients.
1 Positron emission tomography.2 Brain and Mind Research Institute (New York), Centro des Estudios Cientificos (Valdivio, Chile), CNRS/Université Pierre et Marie Curie. 3 Long considered as simple neural substrates, astrocytes or glial cells in reality play an important functional role in brain physiology.
Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.