Glial dysfunction in Huntington’s disease

Normalizing the function of a specific ion channel in astrocytes - a type of glial cell in the brain - can improve motor deficits and prolong survival in a mouse model of Huntington’s disease (HD), reports a study published online in the journal Nature Neuroscience.

HD is an autosomal dominant disorder that is caused by the mutation in a gene called huntingtin. It is a progressive neurodegenerative disorder, characterized by movement and cognitive deficits. A region of the brain called the striatum is particularly susceptible in HD, and, as such, the disease is characterized by dysfunction and death of medium spiny neurons (MSNs) in the striatum; neurons that are critical to initiate and coordinate movements. The role of astrocytes- one of the most abundant non-neuronal cells found the mammalian brain - in HD is however not clear. Baljit Khakh, Michael Sofroniew and colleagues found in several mouse models of HD that astrocytes with mutant huntingtin have reduced levels of a potassium ion channel called Kir4.1, causing an ionic disturbance in areas outside of the cell. They note that this imbalance increases MSN neuron excitability. When the team artificially increased Kir4.1 in astrocytes, they found that the locomotor deficits and premature death seen in HD mouse models were partially alleviated.

This study identifies a potential new therapeutic target for HD, and also suggests that non-neuronal cells can greatly influence the pathology of this disease.