CGRP and CGRP receptors in human and rhesus monkey cerebellum

Eftekhari, Sajedeh; Salvatore, CA; Connolly, BM; O'Malley, Stacey; Miller, PJ; Zeng, Zhizhen; Edvinsson, Lars

doi:10.1186/1129-2377-14-s1-p91

Cited by 2 publications

(4 citation statements)

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“…Later, studies updated the distribution of CGRP in the cytoplasm of Purkinje cell bodies as grains and not in dendrites, axons, nor other cells in rats (Edvinsson et al, 2011 ; Warfvinge and Edvinsson, 2019 ; Warfvinge et al, 2019 ). In the rat MN, CGRP is localized in the cell somas of large neurons as grains (Warfvinge and Edvinsson, 2019 ; Figure 2 ); however, in primates, CGRP is distributed in the cytoplasm of cell bodies and dendrites of Purkinje cells, and cells in the molecular layer (Eftekhari et al, 2013a , b ). There is no description of CGRP distribution in the MN of the primate cerebellum (Eftekhari et al, 2013a , b ).…”

Section: The Cerebellum Contains Cgrp and Abundant Cgrp Binding Sitesmentioning

confidence: 99%

“…In the rat MN, CGRP is localized in the cell somas of large neurons as grains (Warfvinge and Edvinsson, 2019 ; Figure 2 ); however, in primates, CGRP is distributed in the cytoplasm of cell bodies and dendrites of Purkinje cells, and cells in the molecular layer (Eftekhari et al, 2013a , b ). There is no description of CGRP distribution in the MN of the primate cerebellum (Eftekhari et al, 2013a , b ). The difference might be attributed to species, or as suggested by authors, technical reasons (Eftekhari et al, 2013b ).…”

Section: The Cerebellum Contains Cgrp and Abundant Cgrp Binding Sitesmentioning

confidence: 99%

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Involvement of the cerebellum in migraine

Wang

Tutt

Dorricott

et al. 2022

Front. Syst. Neurosci.

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Migraine is a disabling neurological disease characterized by moderate or severe headaches and accompanied by sensory abnormalities, e.g., photophobia, allodynia, and vertigo. It affects approximately 15% of people worldwide. Despite advancements in current migraine therapeutics, mechanisms underlying migraine remain elusive. Within the central nervous system, studies have hinted that the cerebellum may play an important sensory integrative role in migraine. More specifically, the cerebellum has been proposed to modulate pain processing, and imaging studies have revealed cerebellar alterations in migraine patients. This review aims to summarize the clinical and preclinical studies that link the cerebellum to migraine. We will first discuss cerebellar roles in pain modulation, including cerebellar neuronal connections with pain-related brain regions. Next, we will review cerebellar symptoms and cerebellar imaging data in migraine patients. Lastly, we will highlight the possible roles of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine symptoms, including preclinical cerebellar studies in animal models of migraine.

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Section: The Cerebellum Contains Cgrp and Abundant Cgrp Binding Sitesmentioning

confidence: 99%

Section: The Cerebellum Contains Cgrp and Abundant Cgrp Binding Sitesmentioning

confidence: 99%

Involvement of the cerebellum in migraine

Wang

Tutt

Dorricott

et al. 2022

Front. Syst. Neurosci.

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“…Curiously, the cerebellum has the highest binding density to CGRP receptor PET ligands in human and rhesus brains (59,60). The canonical CGRP receptor subunits, receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor (CLR), are localized in the human, rhesus and rat cerebellar cortex (61)(62)(63)(64)(65)(66) and in the medial cerebellar nuclei (MN, also known as fastigial nuclei in humans) of rats (65). CGRP is also distributed in the cerebellar cortex (61,62,(65)(66)(67) and the MN (65).…”

Section: Introductionmentioning

confidence: 99%

“…The canonical CGRP receptor subunits, receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor (CLR), are localized in the human, rhesus and rat cerebellar cortex (61)(62)(63)(64)(65)(66) and in the medial cerebellar nuclei (MN, also known as fastigial nuclei in humans) of rats (65). CGRP is also distributed in the cerebellar cortex (61,62,(65)(66)(67) and the MN (65). In addition, as one of the three deep cerebellar nuclei, the MN receives sensory information via vestibular nuclei (68) and projects to migraine-related brain regions including the thalamus (69).…”

Section: Introductionmentioning

confidence: 99%

CGRP Administration into the Cerebellum Evokes Migraine-like Behaviors Predominately in Female Mice

Duong

Rea

Waite

et al. 2022

Preprint

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The neuropeptide calcitonin gene-related peptide (CGRP) is a major player in migraine pathophysiology. Previous preclinical studies demonstrated that intracerebroventricular administration of CGRP caused migraine-like behaviors in mice, but the sites of action in the brain remain unidentified. The cerebellum has the most CGRP binding sites in the central nervous system and is increasingly recognized as both a sensory and motor integration center. The objective of this study was to test whether the cerebellum, particularly the medial cerebellar nuclei (MN), might be a site of CGRP action. In this study, CGRP was directly injected into the right MN of C57BL/6J mice via a cannula. A battery of behavioral tests was done to assess migraine-like behaviors. CGRP caused light aversion measured as decreased time in the light zone even with dim light. The mice also spent more time resting in the dark zone, but not the light, along with decreased rearing and transitions between zones. These behaviors were similar for both sexes. In contrast, significant responses to CGRP were seen only with female mice in the open field assay, von Frey test, and automated squint assay, indicating anxiety, tactile hypersensitivity, and spontaneous pain, respectively. In male mice, the responses had the same trend as females but did not reach statistical significance. No detectable effect of CGRP on gait was observed in either sex. These results suggest that CGRP in the MN causes light aversion in males, while in females, light aversion is accompanied by increased anxiety, tactile hypersensitivity, and spontaneous pain. A caveat is that we cannot exclude contributions from other cerebellar regions in addition to the MN due to diffusion of the injected peptide. These results reveal the cerebellum as a new site of CGRP actions that may contribute to migraine pathophysiology and possibly its prevalence in females.

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CGRP and CGRP receptors in human and rhesus monkey cerebellum

Cited by 2 publications

References 0 publications

Involvement of the cerebellum in migraine

Involvement of the cerebellum in migraine

CGRP Administration into the Cerebellum Evokes Migraine-like Behaviors Predominately in Female Mice

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