Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice.
Neurobiol Dis
; 24(2): 334-44, 2006 Nov.
Article
en En
| MEDLINE
| ID: mdl-16956767
ABSTRACT
The M5 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 M5 receptor may represent an attractive novel therapeutic target to ameliorate memory deficits caused by impaired cerebrovascular function.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Arterias Cerebrales
/
Trastornos Cerebrovasculares
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Trastornos del Conocimiento
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Enfermedades Neurodegenerativas
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Receptor Muscarínico M5
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón