Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition

Skupio, Urszula; Welte, Julia; Serrat, Román; Eraso-Pichot, Abel; Julio‐Kalajzić, Francisca; Gisquet, Doriane; Cannich, Astrid; Delcasso, Sebastien; Matías, Isabelle; Fundazuri, Unai B.; Pouvreau, Stéphane; Zottola, Antonio C. Pagano; Lavanco, Gianluca; Drago, Filippo; Azúa, Iñigo Ruı́z de; Lutz, Beat; Bellocchio, Luigi; Busquets-García, Arnau; Chaouloff, Francis; Marsicano, Giovanni

doi:10.1016/j.neuron.2023.04.001

Cited by 6 publications

(5 citation statements)

References 53 publications

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“…Jimenez-Blasco et al reported similar effects on complex I but related them to mtCB1R present in astrocytes [25]. Skupio et al proposed that mtCB1R modulates calcium levels in brain circuits, regulating the effects of stress and cortisone in mice tested for novel object recognition [26]. Another investigation linking mtCB1R to cannabinoid effects was conducted by Soria-Gomez et al, showing that mtCB1R decreases synaptic transmission and induces catalepsy [27].…”

Section: Intracellular Organelle-associated Cb1rmentioning

confidence: 97%

“…Using this strain, Jimenez-Blasco et al showed a link between astroglial mitochondria and cannabinoid effects [25]. [27] mtCB1R mediates corticosteroneinduced memory impairment [26] Astroglial mtCB1R reduces mitochondrial respiration with complex I destabilization [25] C57BL/6N GFAP 2 -CB1R-KO Specific impairment of mtCB1R and of cannabinoid effects on mitochondrial dynamics but no influence on CB1R general functions Astroglial mtCB1R reduces mitochondrial respiration with complex I destabilization [25] DN 22 -CB1R 1 : mutant version of CB1R protein lacking the first 22 amino acids; GFAP 2 : glial fibrillary acidic protein.…”

Section: Mtcb1r Modelsmentioning

confidence: 99%

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Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Kouchaeknejad,

Van Der Walt,

De Donato

et al. 2023

IJMS

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As central nervous system (CNS)-related disorders present an increasing cause of global morbidity, mortality, and high pressure on our healthcare system, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS) is a critical network of endogenous compounds, receptors, and enzymes that contribute to CNS development and regulation. Given its multifaceted involvement in neurobiology and its significance in various CNS disorders, the ECS as a whole is considered a promising therapeutic target. Despite significant advances in our understanding of the ECS’s role in the CNS, its complex architecture and extensive crosstalk with other biological systems present challenges for research and clinical advancements. To bridge these knowledge gaps and unlock the full therapeutic potential of ECS interventions in CNS-related disorders, a plethora of molecular–genetic tools have been developed in recent years. Here, we review some of the most impactful tools for investigating the neurological aspects of the ECS. We first provide a brief introduction to the ECS components, including cannabinoid receptors, endocannabinoids, and metabolic enzymes, emphasizing their complexity. This is followed by an exploration of cutting-edge imaging tools and genetic models aimed at elucidating the roles of these principal ECS components. Special emphasis is placed on their relevance in the context of CNS and its associated disorders.

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Section: Intracellular Organelle-associated Cb1rmentioning

confidence: 97%

Section: Mtcb1r Modelsmentioning

confidence: 99%

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Kouchaeknejad,

Van Der Walt,

De Donato

et al. 2023

IJMS

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“…Blockade of the IFN-I receptor (IFNAR) rescues memory and synaptic de cits by inhibiting neuroin ammation [34]. Also the pro-in ammatory factors TNF-α, IL-1β and LPS can upregulate the stress-related hormone corticosterone [36], which also negatively affects memory [37].…”

Section: Crd Exhibits the Most Extensive And Pronounced Adverse Impac...mentioning

confidence: 99%

Disruption of the Circadian Rhythm Is Exacerbated by Aging and Ameliorated by Time- restricted Feeding

Huo,

Liu,

et al. 2024

Preprint

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Background: Circadian rhythms exist across species, and circadian rhythm disorder (CRD) occurs in people of all ages and is prevalent in those with age-related neurodegenerative diseases. The gut microbiota changes with age and a significant proportion of gut microbes show circadian rhythms in their homeostasis. Dysregulation of gut microbial homeostasis is likewise a neurodegenerative disease trigger. Results: In this study, to investigate the relationship between aging, CRD, and the gut microbes, we created a model of CRD by controlling the light/dark cycle, and found that aging aggravated their cognitive impairment and mood disorders. This was accompanied by a loss of gut microbial homeostasis, impairment of the intestinal barrier, and systemic inflammation in aged mice with CRD. The abnormal expression pattern of circadian genes underpin the age-related expression pattern of ifi27l2, thereby exacerbating oxidative stress. In addition, time-restricted feeding (TRF) ameliorated the negative effects of CRD in aged mice by enriching Akkermansia_muciniphilaand inhibiting the NOD-like signaling pathway. Conclusion: Aged mice show more severe impairments in response to stress, likely due to inflammation from gut microbes and circadian gene dysregulation. Maintaining a regular eating schedule can help reduce these effects.

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“…Previous studies have demonstrated that astrocytes have a relatively low expression of CB1 receptors (CB1Rs) (Covelo et al, 2021). However, the functionality of astrocytic CB1Rs is crucial for various physiological changes in synaptic transmission, synaptic plasticity, and behavior (Baraibar et al, 2022;Covelo & Araque, 2018;Gómez-Gonzalo et al, 2015;Martin-Fernandez et al, 2017a;Navarrete & Araque, 2010a;Robin et al, 2018;Serrat et al, 2022;Skupio et al, 2023). Activation of CB1Rs in astrocytes and the subsequent mobilization of intracellular calcium play a vital role in modulating synaptic transmission and plasticity (Covelo & Araque, 2018;Gómez-Gonzalo et al, 2015;Martin-Fernandez et al, 2017b;Navarrete & Araque, 2010b).…”

Section: Hippocampal Astrocytesmentioning

confidence: 99%

“…The endocannabinoid system is a significant intercellular signaling system with crucial function in the regulation of synaptic plasticity and control of behavior throughout the central nervous system (Ahn et al, 2008;Alger & Kim, 2011;Castillo et al, 2012;Di Marzo, 2009;Marcus et al, 2020;Martin-Fernandez et al, 2017a;Ohno-Shosaku & Kano, 2014;Piomelli, 2003;Robin et al, 2018;Serrat et al, 2022;Skupio et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Distinct endocannabinoids specifically signal to astrocytes and neurons

Noriega-Prieto,

Falcón-Moya,

Eraso-Pichot

et al. 2023

Preprint

Self Cite

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The endocannabinoid system is an essential intercellular signaling mechanism with a decisive role in many physiological functions of the brain. Endocannabinoids (eCBs), directly acting on presynaptic neuronal CB1 receptors (CB1Rs), can inhibit neurotransmitter release. In addition, they can potentiate adjacent synapses, inducing lateral regulation of synaptic transmission through astrocyte CB1Rs. In contrast to most, if not all, neurotransmitter systems, the eCB system involves two distinct ligands, Anandamide and 2-Arachidonoylglycerol (AEA and 2AG), and a single receptor (CB1R). The physiological meaning of this particularity remains unknown. Here we show that different eCBs are signaling both astrocytes and neurons, inducing distinct and contrasting synaptic regulation. Combining two-photon with pharmacological and optogenetic approaches and transgenic mice for the synthesis enzyme of both eCBs, we have found that the absence of 2-AG synthesis abolished the inhibitory effect, which was mediated exclusively by neuronal mechanisms. However, the absence of AEA synthesis prevents the lateral potentiation mediated by astrocyte calcium mobilization. Together this indicates that 2-AG signals to neurons, decreasing neurotransmitter release, while AEA signals to astrocytes and induces lateral potentiation. Additionally, AEA synthesis is required for the synaptic potentiation induced by spike-timing-dependent plasticity, as well as astrocyte CB1R, indicating that distinct eCBs-signaling influences neuronal plasticity. We conclude that 2-AG and AEA induce distinct and contrasting synaptic regulation through CB1R in different cell types.

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Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition

Cited by 6 publications

References 53 publications

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS

Disruption of the Circadian Rhythm Is Exacerbated by Aging and Ameliorated by Time- restricted Feeding

Distinct endocannabinoids specifically signal to astrocytes and neurons

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