CGRP in a gene–environment interaction model for depression: effects of antidepressant treatment

Angelucci, Francesco; Ellenbroek, Bart; Khoury, Aram El; Mathé, Aleksander A.

doi:10.1017/neu.2018.31

Cited by 18 publications

(17 citation statements)

References 51 publications

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“…It has also been found to stimulate hippocampal neurogenesis and angiogenesis [38]. These observations have strengthened the notion that it might be involved in cognitive and mood disorders [69]. Data coming from experiments on intracerebroventricular injection in murine models have associated CGRP-alpha release to profound behavioral changes deriving from an influence on monoaminergic projections [70].…”

Section: Cgrp: General Physiology and Influence On Ad Pathogenesismentioning

confidence: 89%

Vasoactive neuropeptides and Alzheimer’s disease: a systematic review focusing on calcitonin gene-related peptide

Papiri¹,

Luzzi²,

Marcucci³

et al. 2021

J. Integr. Neurosci.

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Vasoactive peptides constitute a heterogenous family of mediators exerting various physiological functions, mostly studied for their vasotropic effects and role as peripheral neurotransmitters/neuromodulators, mainly involved in nociceptive transmission modulation. They have been divided into vasodilatory or vasoconstrictive peptides, according to their predominant effects on vascular tone. Recent research has shown in the Central Nervous System effects as transmitters and "growth factor-like" signals. Therefore, deregulation of their signaling systems has been thought to play a role in neural cell death and in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease, since these peptides can regulate neuronal stress signaling, survival cascades, synaptic plasticity. This review considers evidence about the implication of neuropeptide systems in Alzheimer's disease while focusing mainly on calcitonin gene-related peptide-alpha. In vitro and in vivo studies have shown potential implications in its pathogenesis. It has been possibly proposed as a neuroprotective agent, considering not only its pleiotropic actions on blood vessels, neurovascular coupling, energy metabolism, but also its potential actions on neuronal, glial, and immune system stress signaling, which might also derive from its structural homology to amylin. Amylin signaling is thought to be disrupted in Alzheimer's disease, and amylin itself takes part in the composition of senile plaques. Calcitonin gene-related peptide-containing systems seem more closely related to Alzheimer's disease pathogenesis than other neuropeptidergic systems, and their regulation might represent an interesting mechanism in developing novel therapeutic approaches.

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Section: Cgrp: General Physiology and Influence On Ad Pathogenesismentioning

confidence: 89%

Vasoactive neuropeptides and Alzheimer’s disease: a systematic review focusing on calcitonin gene-related peptide

Papiri¹,

Luzzi²,

Marcucci³

et al. 2021

J. Integr. Neurosci.

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“…We discovered that different responses were elicited in MS with respect to n-MS FSL rats. Our previous studies investigated the neurochemical, behavioural, and molecular responses of this rodent model of MDD to antidepressant treatments [39][40][41][42][74][75][76][77]. Our previous findings suggested an association between MS FSL animal behaviours and treatment-resistant MDD [38].…”

Section: Genes Flinders Sensitive Rats (Es Nt)mentioning

confidence: 91%

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Carboni

Pischedda

Piccoli

et al. 2020

Cells

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The Negr1 gene has been significantly associated with major depression in genetic studies. Negr1 encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate the expression of genes belonging to Negr1-Fgfr2 pathway in Flinders sensitive line (FSL) rats, in a corticosterone-treated mouse model of depression, and in mouse primary neurons. Negr1 and Adam10 were the genes mostly affected by antidepressant treatment, and in opposite directions. Negr1 was down-regulated by escitalopram in the hypothalamus of FSL rats, by fluoxetine in the hippocampal dentate gyrus of corticosterone-treated mice, and by nortriptyline in hippocampal primary neurons. Adam10 mRNA was increased by nortriptyline administration in the hypothalamus, by escitalopram in the hippocampus of FSL rats, and by fluoxetine in mouse dorsal dentate gyrus. Similarly, nortriptyline increased Adam10 expression in hippocampal cultures. Fgfr2 expression was increased by nortriptyline in the hypothalamus of FSL rats and in hippocampal neurons. Lsamp, another IgLON family protein, increased in mouse dentate gyrus after fluoxetine treatment. These findings suggest that Negr1-Fgfr2 pathway plays a role in the modulation of synaptic plasticity induced by antidepressant treatment to promote therapeutic efficacy by rearranging connectivity in corticolimbic circuits impaired in depression.

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“…Our previous study reported that the CGRP mRNA level in the hippocampus significantly decreased after 15-day chronic restraint stress exposure, and CGRP intracerebroventricular administration improved depressive-like behavior in C57BL6J mice (Hashikawa-Hobara et al, 2015). In contrast, in the genetic depressive rat model with maternal separation, CGRP levels were elevated in the frontal cortex, hippocampus, and amygdala (Angelucci et al, 2019). In addition, major depressive disorder patients expressed higher CGRP levels in plasma (Hartman et al, 2006).…”

Section: Introductionmentioning

confidence: 95%

CGRP overexpression does not alter depression-like behavior in mice

Hashikawa-Hobara¹,

Otsuka²,

Okujima³

et al. 2021

PeerJ

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Background The calcitonin gene-related peptide (CGRP) is a neuropeptide that is released from capsaicin-sensitive nerves as a potent vasodilator involved in nociceptive transmission. While CGRP has been rigorously studied for its role in migraines owing to its vasodilation and inflammation activities, the effects of CGRP overexpression on depressive-like behaviors remain insufficiently understood. Methods In the present study, we performed a battery of behavioral tests, including the social interaction test, open field test, and sucrose preference test, to evaluate social defeat stress using male C57BL6J or CGRP overexpression in transgenic (Tg) mice (CGRP Tg). We performed mRNA and protein analyses on the brain-derived neurotrophic factor (BDNF), phosphorylated Akt, mTOR, and p70S6K in the hippocampi. Results CGRP Tg mice showed increased levels of Bdnf mRNAs, low locomotor activity, and no deficits in social interaction, which indicate that CGRP Tg mice exhibit stress resistance and not depression. However, the open field test significantly decreased after 15-day social defeat stress exposure. We also evaluated depressive-like behavior using the sucrose preference and social interaction tests. Our data indicate that defeated CGRP Tg mice exhibited a depressive-like phenotype, which was inferred from increased social avoidance and reduced sucrose preference compared with non-defeated controls. Although stress exposure did not change the BDNF levels in CGRP Tg mice, it significantly decreased the expression levels of p-Akt, p-mTOR and p-p70S6K in the mice hippocampi. We conclude that CGRP-overexpressing Tg mice have normal sensitivity to stress and down-regulated hippocampal Akt/mTOR/p70S6K pathways.

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CGRP in a gene–environment interaction model for depression: effects of antidepressant treatment

Cited by 18 publications

References 51 publications

Vasoactive neuropeptides and Alzheimer’s disease: a systematic review focusing on calcitonin gene-related peptide

Vasoactive neuropeptides and Alzheimer’s disease: a systematic review focusing on calcitonin gene-related peptide

Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

CGRP overexpression does not alter depression-like behavior in mice

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