Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer's disease

Rodrı́guez-Puertas, Rafael; Pascual, Julio; Vilaró, M. Teresa; Pazos, Ángel

doi:10.1002/(sici)1098-2396(199708)26:4<341::aid-syn2>3.0.co;2-6

Cited by 105 publications

(47 citation statements)

References 80 publications

(109 reference statements)

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“…In aged rats with a decline in memory and adult-onset cognitive dysfunction, the densities of M1 and M4 receptors were profoundly decreased in brain regions including the Cornu Ammonis area 1 (CA1) and the frontal and occipital cortices (Tayebati et al, 2006). In Alzheimer's and Parkinson's disease patients with impaired cognitive function, the expression of muscarinic receptors was found to be decreased in the brain (Rodriguez-Puertas et al, 1997;Araki et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

et al. 2014

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. (2014). Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: the association with improvements in long-term memory. Neuroscience, 267 57-66.Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: the association with improvements in long-term memory AbstractBackground It is believed that muscarinic M1/4 receptors are closely correlated to the dopaminergic system and are strongly involved in the pathogenesis of Parkinson's disease (PD). In addition to regulating lipid metabolism and protection from stroke, statins have been used to regulate the declined cognition. We aimed to explore the regional changes in M1/4 receptors in the 6-hydroxydopamine (6-OHDA)-lesioned rat brain. Methods PD rat model was set up by injecting 6-OHDA into the unilateral medial forebrain bundle; while simvastatin (10 mg/kg/day) or saline was orally administrated for 3 weeks, respectively. Long-term memory was measured using the Morris water maze.[3H]pirenzepine binding autoradiography was applied to investigate the alterations of M1/4 receptors in the PD rat brains. Results 6-OHDA induced long-term memory deficits along with downregulation of M1/4 receptors in the hippocampus, the medial amygdala, the posteromedial cortical and the piriform cortex; simvastatin administration significantly ameliorated the impaired memory and reversed the downregulation of M1/4 receptors in the examined brain regions. Profound positive correlations were verified between the decline in long-term memory activity and the restoration of M1/4 receptors in different brain regions after simvastatin treatment. Conclusions/significance Our results provide strong evidence that M1/4 receptor modulation after simvastatin administration did, at least partially, contribute to the improvement in the long-term memory in 6-OHDA-induced PD rats. These results provide a possible mechanism for simvastatin treatment in psycho-neurological diseases such as PD via M1/4 receptors.

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Section: Introductionmentioning

confidence: 99%

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

et al. 2014

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“…In fact, malfunction of the cholinergic system in some mental disorders causes memory impairment (Blokland, 1996). In Alzheimer's disease, it has been reported that cholinergic terminals are lost and mAChR densities decrease in the brain, including the hippocampus (Rodríguez-Puertas et al, 1997). Furthermore, an aging-related decrease in the M 1 mAChR density has been found in the hippocampal CA1 region (Tayebati et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Synaptic Plasticity by Physiological Activation of M₁Muscarinic Acetylcholine Receptors in the Mouse Hippocampus

Shinoe¹,

Matsui²,

Taketo³

et al. 2005

J. Neurosci.

235

179

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The muscarinic acetylcholine receptor (mAChR) has been considered one of the neurotransmitter receptors regulating hippocampal synaptic plasticity, which likely plays a critical role in learning and memory. In previous studies, however, muscarinic agonists were used at relatively high concentrations, and the subtype selectivity of muscarinic antagonists was not satisfactory. Thus, it remains to be answered whether physiological levels of ACh are involved in the regulation of synaptic plasticity and which mAChR subtypes are responsible for such effects. We found in this study that a low concentration (50 nM) of carbachol enhanced long-term potentiation (LTP) of excitatory synaptic transmission in mouse hippocampal slices. Notably, this enhancing effect was abolished in M 1 mAChR knock-out (KO) but not in M 3 mAChR KO mice, although LTP itself was intact in both mutant mice. Furthermore, we found that repetitive stimulation in the stratum oriens, which presumably triggered the release of endogenous ACh from cholinergic terminals, could enhance LTP in wild-type mice but not in M 1 mAChR KO mice. These results suggest that physiologically released ACh from cholinergic fibers modulates hippocampal synaptic plasticity through the postsynaptic M 1 mAChR activation.

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“…The loss of presynaptic cholinergic terminals observed in Alzheimer's disease patients results in decreased release of endogenous acetylcholine (Rodríguez-Puertas et al, 1997). This subsequently reduces the magnitude of activation of postsynaptic M 1 muscarinic acetylcholine receptors (M 1 mAChR) involved in learning and memory through modulation of synaptic plasticity in the hippocampus (Ladner and Lee, 1998).…”

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confidence: 99%

Long-Term Changes in the Muscarinic M₁ Receptor Induced by Instantaneous Formation of Wash-Resistant Xanomeline-Receptor Complex

Lorme

Grant

Noetzel

et al. 2007

J Pharmacol Exp Ther

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Unlike other M 1 muscarinic acetylcholine receptor agonists, xanomeline demonstrates a unique mode of binding to the receptor. It not only binds reversibly to the receptor's conventional orthosteric site but also binds persistently at a secondary binding domain(s) on the M 1 receptor. This results in persistent activation of the receptor even after extensive washout, and allosteric modulation of the orthosteric site. In the current study, we investigated how the effects of very brief exposure (1 min) of intact Chinese hamster ovary cells expressing M 1 receptors to xanomeline followed by washout change with time. Pretreatment with xanomeline for 1 min resulted in a concentration-dependent wash-resistant inhibition of [ 3 H]N-methylscopolamine (NMS) binding, with a lower potency than that observed in the continuous presence of xanomeline in the binding assay medium. This effect was associated with washresistant receptor activation. Incubation of pretreated and washed cells in control medium for 24 h transformed the monophasic xanomeline wash-resistant binding curve to one that exhibits two distinct potencies. This was the result of the appearance of a new very high-potency binding component without a change in the low-potency state. The delayed effects of persistently bound xanomeline are mainly due to reduction of the maximal binding of [ 3 H]NMS without a change in its affinity. These treatment conditions also reversed persistent receptor activation by xanomeline. Our results imply that brief exposure to xanomeline followed by washing and prolonged waiting may result in delayed receptor desensitization accompanied by internalization or down-regulation.

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Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer's disease

Cited by 105 publications

References 80 publications

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

Modulation of Synaptic Plasticity by Physiological Activation of M₁Muscarinic Acetylcholine Receptors in the Mouse Hippocampus

Long-Term Changes in the Muscarinic M₁ Receptor Induced by Instantaneous Formation of Wash-Resistant Xanomeline-Receptor Complex

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Autoradiographic distribution of M1, M2, M3, and M4 muscarinic receptor subtypes in Alzheimer's disease

Cited by 105 publications

References 80 publications

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

Modulation of Synaptic Plasticity by Physiological Activation of M1Muscarinic Acetylcholine Receptors in the Mouse Hippocampus

Long-Term Changes in the Muscarinic M1 Receptor Induced by Instantaneous Formation of Wash-Resistant Xanomeline-Receptor Complex

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Product

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Modulation of Synaptic Plasticity by Physiological Activation of M₁Muscarinic Acetylcholine Receptors in the Mouse Hippocampus

Long-Term Changes in the Muscarinic M₁ Receptor Induced by Instantaneous Formation of Wash-Resistant Xanomeline-Receptor Complex