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Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice.
Neuromolecular Med 2018; 20(1):133-146NM

Abstract

Autism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf/J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach. Here, we explored whether resveratrol treatment decreases neuroimmune dysregulation mediated through toll-like receptor (TLR4) and nuclear factor-κB (NF-κB) signaling pathway in BTBR mice. We investigated the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-κB, and inducible nitric oxide synthase (iNOS or NOS2) levels in CD4 spleen cells. We also assessed the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-κB, iNOS, and cyclooxygenase (COX-2) mRNA expression levels in the brain tissue. We further explored TLR2, TLR4, NF-κB, iNOS, and COX-2 protein expression levels in the brain tissue. Resveratrol treatment on BTBR mice significantly decreased CD4+TLR2+, CD4+TLR3+, CD4+TLR4+ CD4+NF-κB+, and CD4+iNOS+ levels in spleen cells. Resveratrol treatment on BTBR mice decreased TLR2, TLR3, TLR4, NF-κB, iNOS, and COX-2 mRNA expression levels in brain tissue. Moreover, resveratrol treatment resulted in decreased protein expression of TLR2, TLR3, TLR4, NF-κB, iNOS, and COX-2 in brain tissue. Taken together, these results indicate that resveratrol treatment improves neuroimmune dysregulation through the inhibition of proinflammatory mediators and TLRs/NF-κB transcription factor signaling, which might be help devise future therapies for neuroimmune disorders.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. s_fayazahmad@yahoo.com.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29468499

Citation

Ahmad, Sheikh F., et al. "Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice." Neuromolecular Medicine, vol. 20, no. 1, 2018, pp. 133-146.
Ahmad SF, Ansari MA, Nadeem A, et al. Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice. Neuromolecular Med. 2018;20(1):133-146.
Ahmad, S. F., Ansari, M. A., Nadeem, A., Alzahrani, M. Z., Bakheet, S. A., & Attia, S. M. (2018). Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice. Neuromolecular Medicine, 20(1), pp. 133-146. doi:10.1007/s12017-018-8483-0.
Ahmad SF, et al. Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice. Neuromolecular Med. 2018;20(1):133-146. PubMed PMID: 29468499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice. AU - Ahmad,Sheikh F, AU - Ansari,Mushtaq A, AU - Nadeem,Ahmed, AU - Alzahrani,Mohammad Z, AU - Bakheet,Saleh A, AU - Attia,Sabry M, Y1 - 2018/02/21/ PY - 2017/09/13/received PY - 2018/02/16/accepted PY - 2018/2/23/pubmed PY - 2019/8/14/medline PY - 2018/2/23/entrez KW - Autism KW - BTBR T+ Itpr3tf/J and C57BL/6 KW - Resveratrol KW - Spleen and brain KW - TLRs/NF-κB transcription factor SP - 133 EP - 146 JF - Neuromolecular medicine JO - Neuromolecular Med. VL - 20 IS - 1 N2 - Autism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf/J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach. Here, we explored whether resveratrol treatment decreases neuroimmune dysregulation mediated through toll-like receptor (TLR4) and nuclear factor-κB (NF-κB) signaling pathway in BTBR mice. We investigated the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-κB, and inducible nitric oxide synthase (iNOS or NOS2) levels in CD4 spleen cells. We also assessed the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-κB, iNOS, and cyclooxygenase (COX-2) mRNA expression levels in the brain tissue. We further explored TLR2, TLR4, NF-κB, iNOS, and COX-2 protein expression levels in the brain tissue. Resveratrol treatment on BTBR mice significantly decreased CD4+TLR2+, CD4+TLR3+, CD4+TLR4+ CD4+NF-κB+, and CD4+iNOS+ levels in spleen cells. Resveratrol treatment on BTBR mice decreased TLR2, TLR3, TLR4, NF-κB, iNOS, and COX-2 mRNA expression levels in brain tissue. Moreover, resveratrol treatment resulted in decreased protein expression of TLR2, TLR3, TLR4, NF-κB, iNOS, and COX-2 in brain tissue. Taken together, these results indicate that resveratrol treatment improves neuroimmune dysregulation through the inhibition of proinflammatory mediators and TLRs/NF-κB transcription factor signaling, which might be help devise future therapies for neuroimmune disorders. SN - 1559-1174 UR - https://www.unboundmedicine.com/medline/citation/29468499/Resveratrol_Improves_Neuroimmune_Dysregulation_Through_the_Inhibition_of_Neuronal_Toll_Like_Receptors_and_COX_2_Signaling_in_BTBR_T+_Itpr3tf/J_Mice_ L2 - https://dx.doi.org/10.1007/s12017-018-8483-0 DB - PRIME DP - Unbound Medicine ER -