Calcium on the brain.

Brian Bacskai has a lovely paper on how Alzheimer's disease changes astrocytic calcium signaling. (Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 27 February 2009, Vol. 323. no. 5918, pp. 1211 - 1215. DOI:10.1126/science.1169096)
They find that in a mouse model of AD that amyloid-beta plaques are foci for the initiation of calcium waves in the astrocyte network. Further, diseased mice have higher resting calcium than normal mice. They use a well established mouse model of AD (APPswe:PSdeltaE9, this has APP Swedish mutations Lys670Asn & Met671Leu, and PS1 Pro264Leu, and is available from Jackson Labs). The advantage of this model is that plaques occur early in life (4.5 months) so it makes research a bit cheaper to do (lower cage costs). It should be stressed that this model along with most other mouse models of AD do not show neuronal loss. Neuronal death from AD is, of course, the fundamental human problem. Karen Ashe has suggested that such mice are models only of the early stages of AD in humans. So she has recently developed a very cool new mouse model in which plauqes and tangles (hyperphosphorylated tau) are inducible (tet-off system). The Ashe mouse shows neuronal loss. As far as I know this is unique mouse model. Back to Bacskai. He finds that calcium transients in astrocytes occur more frequently in AD than WT mice. These signals are somewhat larger than normal and are synchronous. Finally they are not dependent upon neuronal activity. These results suggest that plaques change the calcium buffering of astrocytes in a significant way. (As a side-note, I talked with the first author, Kishore, at SfN in DC in 2008, who told me no one in his lab though looking at astrocytes was worth while. Not a bad result for such an unpromising start!) Similar results have been reported by Haydon and Nedergaard for epilepsy, linking calcium waves to another disease (note most glia biologists now think that in vitro calcium waves are artifactual). It will be interesting to see what the mechanistic explanation is for these transients, and if more advanced mouse models show similar trends.

Amyloid Plaque and Neurofibrillary Tangle Pathology in a Regulatable Mouse Model of Alzheimer’s Disease. Am. J. Path. (2008) 173:762-772.

Enhanced astrocytic Ca signals contribute to neuronal excitotoxicity after status epilepticus. J. Neurosci. (2007) 27:10674-10684.

An astrocytic basis of epilepsy. Nature Med. (2005) 11:973-981.

Animal models of Alzheimer's disease and frontotemporal dementia. Nature Rev. Neurosci. (2008) 9:532-544.