TY - JOUR
T1 - Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice
AU - Araya, Runa
AU - Noguchi, Takanori
AU - Yuhki, Munehiro
AU - Kitamura, Naohito
AU - Higuchi, Makoto
AU - Saido, Takaomi C.
AU - Seki, Kenjiro
AU - Itohara, Shigeyoshi
AU - Kawano, Masako
AU - Tanemura, Kentaro
AU - Takashima, Akihiko
AU - Yamada, Kazuyuki
AU - Kondoh, Yasushi
AU - Kanno, Iwao
AU - Wess, Jürgen
AU - Yamada, Masahisa
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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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U2 - 10.1016/j.nbd.2006.07.010
DO - 10.1016/j.nbd.2006.07.010
M3 - Article
C2 - 16956767
AN - SCOPUS:33749990044
SN - 0969-9961
VL - 24
SP - 334
EP - 344
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -