PPARγ receptors are involved in the effects of cannabidiol on orofacial dyskinesia and cognitive dysfunction induced by typical antipsychotic in mice

Sonego, Andreza Buzolin; Prado, Douglas da Silva; Guimarães, Francisco Silveira

doi:10.1016/j.pnpbp.2021.110367

Cited by 8 publications

(10 citation statements)

References 57 publications

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“…Our previous study has reported that in both cultured astrocytes and the rat prefrontal cortex, olanzapine increased the expression of IL-1β ( Li et al, 2021c ). Haloperidol increased IL-β in the rat brain ( Sonego et al, 2021 ; Mezzomo et al, 2022 ). These findings suggest that antipsychotics such as olanzapine and haloperidol might significantly affect the NLRP3/caspase-1 signaling, leading to IL-1β production and astrocyte death.…”

Section: Introductionmentioning

confidence: 99%

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

Fan

Zhou

et al. 2022

Front. Aging Neurosci.

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Emerging data indicate that antipsychotic treatment causes brain volume loss and astrocyte death, but the mechanisms remain elusive. Pyroptosis, inflammatory cell death characterized by the formation of inflammatory bodies, increased expression of nod-like receptor proteins (NLRPs) such as NLRP3, and activation of caspases and gasdermin D (GSDMD) are largely associated with innate immunity, inflammation, and cell injury/death. However, the main effect of antipsychotics on astrocyte pyroptotic signaling and the molecular mechanisms remain obscure. In the present study, 72-h treatment with olanzapine, quetiapine, risperidone, or haloperidol significantly decreased the viability of astrocytes. Twenty-four hour treatment with olanzapine, quetiapine, risperidone, or haloperidol dose-dependently increased the protein expression of astrocytic NLRP3, NLRP6, caspase-1, caspase-4, and GSDMD. Co-treatment with a histamine H1 receptor agonist, 2-(3-trifluoromethylphenyl) histamine (FMPH), dose-dependently reduced the increased expression of NLRP3, caspase-1 and GSDMD induced by olanzapine, quetiapine, risperidone, or haloperidol. Moreover, olanzapine, quetiapine, risperidone, or haloperidol treatment induced pore formation in the membranes of astrocytes, and these effects were inhibited by FMPH co-treatment. Taken together, antipsychotic treatment activated astrocyte pyroptotic signaling, and these effects may be related to antipsychotic-induced astrocyte death. H1 receptor activation is an effective treatment strategy to suppress antipsychotic-induced astrocyte pyroptosis and inflammation.

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Section: Introductionmentioning

confidence: 99%

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

Fan

Zhou

et al. 2022

Front. Aging Neurosci.

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“…CBD is known to interact with multiple targets within the CNS to exert its effects ( Esposito et al, 2011 ). CBD has low binding affinity for cannabinoid type 1 and 2 receptors (CB 1 R and CB 2 R, respectively; Khosropoor et al, 2023 ), even though CBD can still exert effects mediated by these receptors ( Bisogno et al, 2001 ; Ryberg et al, 2007 ; Campos et al, 2013 ; Burstein, 2015 ; Boggs et al, 2018 ; Sonego et al, 2021 ). A variety of other non-cannabinoid receptors can be targeted by CBD, including transient receptor potential vanilloid (TRPV) channels ( Bruce-Keller et al, 2008 ), serotonin (5-HT1A) receptors ( Chauhan et al, 2003 ; Long et al, 2010 ), peroxisome proliferator-activated receptor gamma ( PPARγ ; Long et al, 2006 ; Varvel et al, 2006 ; Singh et al, 2018 ), and the cannabinoid-related receptor GPR55 ( Jones and Roberts, 1968 ; Lueptow, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Yadav-Samudrala,

Gorman,

Barmada

et al. 2024

Front. Neurosci.

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BackgroundSome evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice.MethodsTat transgenic mice (female/male) were injected with CBD (3, 10, 30 mg/kg) and assessed for antinociception, activity, coordination, anxiety-like behavior, and recognition memory. Brains were taken to quantify endocannabinoids, cannabinoid receptors, and cannabinoid catabolic enzymes. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex.ResultsTat decreased supraspinal-related nociception and locomotion. CBD and sex had little to no effects on any of the behavioral measures. For the endocannabinoid system male sex was associated with elevated concentration of the proinflammatory metabolite arachidonic acid in various CNS regions, including the cerebellum that also showed higher FAAH expression levels for Tat(+) males. GPR55 expression levels in the striatum and cerebellum were higher for females compared to males. CBD metabolism was altered by sex and Tat expression.ConclusionFindings indicate that acute CBD effects are not altered by HIV Tat, and acute CBD has no to minimal effects on behavior and the endocannabinoid system.

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“…Increased (in comparison to control animals who were only exposed to the vehiculum used) striatal levels of IL-1β were invariably found in rodent models of haloperidol-induced orofacial dyskinesia ( Grover et al, 2013 ; Peroza et al, 2016 ; Thakur et al, 2015 ; Datta et al, 2016 ; Sonego et al, 2018 , 2021 ; Mezzomo et al, 2022 ). Both dyskinesia and IL-1β levels were reduced when the animals received concurrent antioxidant treatment.…”

Section: Biomarkers For Neuroinflammation and Tardive Dyskinesiamentioning

confidence: 99%

“…Both dyskinesia and IL-1β levels were reduced when the animals received concurrent antioxidant treatment. IL-1β levels correlated with the frequency of orofacial movements ( Peroza et al, 2016 ; Sonego et al, 2018 , 2021 ). However, striatal mRNA levels were not altered ( Sonego et al, 2018 ).…”

Section: Biomarkers For Neuroinflammation and Tardive Dyskinesiamentioning

confidence: 99%

Putative role of immune reactions in the mechanism of tardive dyskinesia

Loonen

2023

Brain, Behavior, & Immunity - Health

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PPARγ receptors are involved in the effects of cannabidiol on orofacial dyskinesia and cognitive dysfunction induced by typical antipsychotic in mice

Cited by 8 publications

References 57 publications

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Putative role of immune reactions in the mechanism of tardive dyskinesia

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