The distribution of m4 muscarinic acetylcholine receptors in the islands of Calleja and striatum of rats and cynomolgus monkeys

Wirtshafter, David; Osborn, Catherine V.

doi:10.1016/j.jchemneu.2004.05.007

Cited by 10 publications

(4 citation statements)

References 42 publications

(81 reference statements)

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“…The MSNs can express: i) the excitatory M1 receptor, which activates G q/11 proteins and induces the activation of phospholipase C pathway; ii) the inhibitory M4 receptor, which is coupled to G i/0 proteins and decreases activity of adenylyl cyclase; or iii) both M1 and M4 receptors [ 47 – 49 ]. Furthermore, it has been described a predominant expression of M4 receptor in the striosomal than the matrix compartment [ 50 ], suggesting different physiologic responses related to distinct striatal circuits.…”

Section: Discussionmentioning

confidence: 99%

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

et al. 2018

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The striatum is a complex structure in which the organization in two compartments (striosomes and matrix) have been defined by their neurochemical profile and their input-output connections. The striosomes receive afferences from the limbic brain areas and send projections to the dopamine neurons of the substantia nigra pars compacta. Thereby, it has been suggested that the striosomes exert a limbic control over the motor function mediated by the surrounding matrix. However, the functionality of the striosomes are not completely understood. To elucidate the role of the striosomes on the regulation of the nigral dopamine neurons, we have induced specific ablation of this compartment by striatal injections of the neurotoxin dermorphin-saporin (DS) and dopamine neurotransmission markers have been analyzed by immunohistochemistry. The degeneration of the striosomes resulted in a nigrostriatal projections imbalance between the two striatal compartments, with an increase of the dopamine neurotransmission in the striosomes and a decrease in the matrix. The present results highlight the key function of the striosomes for the maintenance of the striatal dopamine tone and would contribute to the understanding of their involvement in some neurological disorders such as Huntington’s disease.

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Section: Discussionmentioning

confidence: 99%

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

et al. 2018

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“…Unfortunately, lack of receptor subtype selectivity led to undesirable side-effects (gastrointestinal disturbances, blood pressure dysregulation) that rendered xanomeline as an unsuitable candidate for further clinical development (14). M 4 receptors are most highly expressed in brain regions rich in dopamine and dopamine receptors (15,16). Experiments with muscarinic knock out mice have implicated the M 4 receptor subtype in regulating dopaminergic neurons involved in movement control and cognition (17,18); therefore, we reasoned that a highly selective M 4 muscarinic receptor activator may represent a useful candidate for the development of muscarinic-based antipsychotic agents.…”

mentioning

confidence: 99%

Allosteric modulation of the muscarinic M ₄ receptor as an approach to treating schizophrenia

Chan

McKinzie²,

Bose

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

220

249

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“…24216) was used in this study. This commercially available antibody has been extensively used for immunohistochemistry in the rat CNS [32,38-44]. Specificity of the MOR antiserum has been demonstrated previously on the basis of epitope-expressing cell lines, western blotting, and adsorption controls [32,45].…”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical localization of mu opioid receptor in the marginal division with comparison to patches in the neostriatum of the rat brain

et al. 2011

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BackgroundMu opioid receptor (MOR), which plays key roles in analgesia and also has effects on learning and memory, was reported to distribute abundantly in the patches of the neostriatum. The marginal division (MrD) of the neostriatum, which located at the caudomedial border of the neostriatum, was found to stain for enkephalin and substance P immunoreactivities and this region was found to be involved in learning and memory in our previous study. However, whether MOR also exists in the MrD has not yet been determined.MethodsIn this study, we used western blot analysis and immunoperoxidase histochemical methods with glucose oxidase-DAB-nickel staining to investigate the expression of MOR in the MrD by comparison to the patches in the neostriatum.ResultsThe results from western blot analyses revealed that the antibody to MOR detected a 53 kDa protein band, which corresponded directly to the molecular weight of MOR. Immunohistochemical results showed that punctate MOR-immunoreacted fibers were observed in the "patch" areas in the rostrodorsal part of the neostriatum but these previous studies showed neither labelled neuronal cell bodies, nor were they shown in the caudal part of the neostriatum. Dorsoventrally oriented dark MOR-immunoreactive nerve fibers with individual labelled fusiform cell bodies were firstly observed in the band at the caudomedial border, the MrD, of the neostriatum. The location of the MOR-immunoreactivity was in the caudomedial border of the neostriatum. The morphology of the labelled fusiform neuronal somatas and the dorsoventrally oriented MOR-immunoreacted fibers in the MrD was distinct from the punctate MOR-immunoreactive diffuse mosaic-patterned patches in the neostriatum.ConclusionsThe results indicated that MOR was expressed in the MrD as well as in patches in the neostriatum of the rat brain, but with different morphological characteristics. The punctate MOR-immunoreactive and diffuse mosaic-patterned patches were located in the rostrodorsal part of the neostriatum. By contrast, in the MrD, the dorsoventrally parallel oriented MOR-immunoreactive fibers with individual labelled fusiform neuronal somatas were densely packed in the caudomedial border of the neostriatum. The morphological difference in MOR immunoreactivity between the MrD and the patches indicated potential functional differences between them. The MOR most likely plays a role in learning and memory associated functions of the MrD.

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The distribution of m4 muscarinic acetylcholine receptors in the islands of Calleja and striatum of rats and cynomolgus monkeys

Cited by 10 publications

References 42 publications

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

Allosteric modulation of the muscarinic M ₄ receptor as an approach to treating schizophrenia

Immunohistochemical localization of mu opioid receptor in the marginal division with comparison to patches in the neostriatum of the rat brain

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The distribution of m4 muscarinic acetylcholine receptors in the islands of Calleja and striatum of rats and cynomolgus monkeys

Cited by 10 publications

References 42 publications

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway

Allosteric modulation of the muscarinic M 4 receptor as an approach to treating schizophrenia

Immunohistochemical localization of mu opioid receptor in the marginal division with comparison to patches in the neostriatum of the rat brain

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Allosteric modulation of the muscarinic M ₄ receptor as an approach to treating schizophrenia