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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Loss of M(5) muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice.

The M(5) muscarinic acetylcholine receptor (M5R) has been shown to play a crucial role in mediating acetylcholine-dependent dilation of cerebral blood vessels. We show that male M5R(-/-) mice displayed constitutive constriction of cerebral arteries using magnetic resonance angiography in vivo. Male M5R(-/-) mice exhibited a significantly reduced cerebral blood flow (CBF) in the cerebral cortex, hippocampus, basal ganglia, and thalamus. Cortical and hippocampal pyramidal neurons from M5R(-/-) mice showed neuronal atrophy. Hippocampus-dependent spatial and nonspatial memory was also impaired in M5R(-/-) mice. In M5R(-/-) mice, CA3 pyramidal cells displayed a significantly attenuated frequency of the spontaneous postsynaptic current and long-term potentiation was significantly impaired at the mossy fiber-CA3 synapse. Our findings suggest that impaired M5R signaling may play a role in the pathophysiology of cerebrovascular deficits. The M(5) receptor may represent an attractive novel therapeutic target to ameliorate memory deficits caused by impaired cerebrovascular function.[1]

References

  1. Loss of M(5) muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice. Araya, R., Noguchi, T., Yuhki, M., Kitamura, N., Higuchi, M., Saido, T.C., Seki, K., Itohara, S., Kawano, M., Tanemura, K., Takashima, A., Yamada, K., Kondoh, Y., Kanno, I., Wess, J., Yamada, M. Neurobiol. Dis. (2006) [Pubmed]
 
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