Effects of adenosine A2a receptor agonist and antagonist on hippocampal nuclear factor-kB expression preceded by MDMA toxicity

Kermanian, Fatemeh; Soleimani, Mansooreh; Ebrahimzadeh, Alireza; Haghir, Hossein; Mehdizadeh, Mehdi

doi:10.1007/s11011-012-9366-y

Cited by 22 publications

(8 citation statements)

References 93 publications

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“…The A2A receptor antagonist and agonist were each used at a dose of 0.03 mg/kg, in accordance with a previous report [38]. We found that the number of CCR3 + cells and CD8 + T cells expressing CCR3 + increased in the BTBR control and BTBR-SCH-treated mice as compared to that in B6 normal mice (Fig.…”

Section: A2a Receptors Regulate Ccr3 Ccr4 Ccr5 Ccr6 and Ccr7 Chemsupporting

confidence: 87%

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Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

et al. 2017

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Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T Itpr3/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model. A2A receptors have previously been targeted in clinical trials by potential therapeutics with neuroprotective, immunomodulatory, and analgesic properties. In this study, we examined the effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8 T cells in the BTBR autistic mouse model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in brain tissue. Our results showed that CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 production in splenic CD8 T cells decreased significantly in BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH-treated mice. In addition, RT-PCR analysis revealed decreased gene expression levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS-treated mice, whereas these levels were significantly increased in BTBR control and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS decreases C-C and C-X-C chemokine receptor signaling and might therefore provide a unique avenue for developing future therapies for autism and neuroimmunological disorders.

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Section: A2a Receptors Regulate Ccr3 Ccr4 Ccr5 Ccr6 and Ccr7 Chemsupporting

confidence: 87%

“…The volume of drug administered to each mouse was based on its body weight. The doses of SCH and CGS were selected based on the results of the previous study [38].…”

Section: Experimental Designmentioning

confidence: 99%

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

et al. 2017

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“…: RP1100, Solar bio, China). Specific primers for tumor necrosis factor alpha (TNF-a) (5′CCCTGGTACTAACTCCCAGAAA-3′, 5′TGTATGAGAGGGACGGAACC-3′, [ 38 ]), vascular endothelial growth factor (VEGF) (5′ACAGAAGGGGAGCAGAAAGCCCAT-3′, 5′CGCTCTGACCAAGGCTCACAGT-3′, [ 39 ]), tumor suppressor (p53) (5′CCTATCCGGTCAGTTGTTGGA-3′, CCTATCCGGTCAGTTGTT-GGA-3′, [ 40 ]) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) (5′GCAAACCTGGGAATACTTCATGTGACTAAG-3′, 5′ATAGGCAAGGTCAGAATGCACCAGAAGTCC-3′, [ 41 ]) and GAPDH (5′CAACTCCCTCAAGATTGTCAGCAA-3′, 5′GGCATGGACTGTGGTCATGA-3′, [ 42 ]) genes were chosen. Quantitative real-time PCR (qPCR) was performed using QuantiTect SYBR Green qPCR Master Mix in a StepOnePlus Real-Time PCR system (Applied Biosystems, San Francisco, USA) and reaction cycles (Reaction mixtures were incubated for 10 min at 95 °C, followed by 40 cycles of 15 s at 95 °C, 1 min at 60 °C, and, finally, 15 s at 95 °C, 1 min at 60 °C, and 15 s at 95 °C).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights

et al. 2022

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This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.

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“…Even though in the striatum the first A 2A /D 2 antagonistic relationship is predominant, due to the higher distribution of AC V, when AGS3 is upregulated, such as during chronic exposure to addictive drugs, the synergistic interaction between A 2A and D 2 receptors becomes relevant, suggesting that A 2A receptor antagonists may represent a class of drug to combat addiction and relapse ( Ferré et al, 2008b ). In addition, neuroprotection exerted by A 2A receptor agonists seemed to be mediated by an increase in nuclear factor-κB ( Kermanian et al, 2012 , 2013 ; Soleimani et al, 2012 ).…”

Section: Mechanisms Of Adenosine Receptor-mediated Pathways In Drug Amentioning

confidence: 99%

The Role of Adenosine Receptors in Psychostimulant Addiction

et al. 2018

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Adenosine receptors (AR) are a family of G-protein coupled receptors, comprised of four members, named A1, A2A, A2B, and A3 receptors, found widely distributed in almost all human body tissues and organs. To date, they are known to participate in a large variety of physiopathological responses, which include vasodilation, pain, and inflammation. In particular, in the central nervous system (CNS), adenosine acts as a neuromodulator, exerting different functions depending on the type of AR and consequent cellular signaling involved. In terms of molecular pathways and second messengers involved, A1 and A3 receptors inhibit adenylyl cyclase (AC), through Gi/o proteins, while A2A and A2B receptors stimulate it through Gs proteins. In the CNS, A1 receptors are widely distributed in the cortex, hippocampus, and cerebellum, A2A receptors are localized mainly in the striatum and olfactory bulb, while A2B and A3 receptors are found at low levels of expression. In addition, AR are able to form heteromers, both among themselves (e.g., A1/A2A), as well as with other subtypes (e.g., A2A/D2), opening a whole range of possibilities in the field of the pharmacology of AR. Nowadays, we know that adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission and therefore reward systems, being A1 receptors colocalized in heteromeric complexes with D1 receptors, and A2A receptors with D2 receptors. This review documents the present state of knowledge of the contribution of AR, particularly A1 and A2A, to psychostimulants-mediated effects, including locomotor activity, discrimination, seeking and reward, and discuss their therapeutic relevance to psychostimulant addiction. Studies presented in this review reinforce the potential of A1 agonists as an effective strategy to counteract psychostimulant-induced effects. Furthermore, different experimental data support the hypothesis that A2A/D2 heterodimers are partly responsible for the psychomotor and reinforcing effects of psychostimulant drugs, such as cocaine and amphetamine, and the stimulation of A2A receptor is proposed as a potential therapeutic target for the treatment of drug addiction. The overall analysis of presented data provide evidence that excitatory modulation of A1 and A2A receptors constitute promising tools to counteract psychostimulants addiction.

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Effects of adenosine A2a receptor agonist and antagonist on hippocampal nuclear factor-kB expression preceded by MDMA toxicity

Cited by 22 publications

References 93 publications

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights

The Role of Adenosine Receptors in Psychostimulant Addiction

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