Káradóttir R, Hamilton NB, Bakiri Y, Attwell D.
Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter.
Nat Neurosci. 2008 Apr;11(4):450-6.
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Abnormalities of the white matter are a universal component of aging. These white matter changes appear as hyperintensities on T2-weighted MRI sequences or as alterations of anisotropy, diffusivity, or magnetization transfer on more sensitive MRI techniques. They correlate neuropathologically to rarefaction and mild gliosis of the white matter rather than frank infarction (1). Though the cause of white matter change is still not fully defined, its association with microvascular processes such as arteriosclerosis and cerebral amyloid angiopathy suggests a chronic ischemic mechanism, i.e., a kind of slow-developing stroke. Although once thought to be incidental and clinically unimportant, white matter lesions are now recognized for their association with cognitive impairment, depression, and future risk of dementia (2-4). They are more prevalent in Alzheimer disease than similar aged controls (5) and may act in concert with the Alzheimer process to produce worse clinical impairments than either disorder alone (6).
The current paper by Karadottir and colleagues puts a new spin on the pathogenesis of white matter lesions, focusing not on the vessels but on the white matter itself. The authors report a substantial subset of oligodendrocyte precursor cells with synaptic input and the requisite channels for firing action potentials. This class of cells, which remains present in the adult rat, showed increased cell death to ischemic insult. Ischemia-induced cell death was driven not by the action potential machinery (it was insensitive to tetrodotoxin) but rather by glutamate release and possible secondary release of vesicular calcium. Although no evidence was presented to link these findings to age-related abnormalities of white matter, the cells’ sensitivity to low levels of ischemia not injurious to other cell types makes them logical candidates to be involved. The message at this point for investigators of age-related white matter disease is to stay tuned.
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