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Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice.
Behav Brain Res 2019; 364:213-224BB

Abstract

Autism is a neurodevelopmental disease which is characterized by its core behavioral symptoms such as impairment in social interaction and stereotyped repetitive behavior. Th17 immune responses and oxidative stress are reported to be elevated in both human autistic subjects and BTBR T + Itpr3tf/J (BTBR) mice. On the other hand, activation of nuclear factor erythroid 2 related factor (Nrf2), a master transcription factor is essential for the management of anti-inflammatory and antioxidant genes. Sulforaphane activates Nrf2 and thus is considered a potential approach to treat several neurological disorders including autism. In the current work, we used sulforaphane in asocial BTBR mice and its social counterpart C57/BL6 (C57) mice to assess its therapeutic potential and molecular mechanisms (Th17 immune responses, and oxidant-antioxidant balance) through which it acts. Our results demonstrate that BTBR treated with sulforaphane had reduced self-grooming/marble burying behavior, and increased social interaction in three chambered sociability test as compared to untreated BTBR mice. Further, sulforaphane-treated BTBR mice had reduced Th17 immune responses (STAT3, RORC, IL-17 A and IL-23R expression in CD4 + T cells), oxidative stress parameters in neutrophils/cerebellum (NFkB, iNOS, and lipid peroxides). Furthermore, sulforaphane-treated BTBR and C57 mice had upregulated enzymatic antioxidant defenses in neutrophils/cerebellum (SOD, GPx and GR expression and activity). We reason that activation of Nrf2 by sulforaphane corrected Th17 immune dysfunction and oxidant-antioxidant imbalance in periphery and brain in BTBR mice. These mechanisms lead to improvement in autism-like symptoms in BTBR mice.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: anadeem@ksu.edu.sa.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Pub Type(s)

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

Language

eng

PubMed ID

30790585

Citation

Nadeem, Ahmed, et al. "Nrf2 Activator, Sulforaphane Ameliorates Autism-like Symptoms Through Suppression of Th17 Related Signaling and Rectification of Oxidant-antioxidant Imbalance in Periphery and Brain of BTBR T+tf/J Mice." Behavioural Brain Research, vol. 364, 2019, pp. 213-224.
Nadeem A, Ahmad SF, Al-Harbi NO, et al. Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice. Behav Brain Res. 2019;364:213-224.
Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., Attia, S. M., Bakheet, S. A., Ibrahim, K. E., ... Alqinyah, M. (2019). Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice. Behavioural Brain Research, 364, pp. 213-224. doi:10.1016/j.bbr.2019.02.031.
Nadeem A, et al. Nrf2 Activator, Sulforaphane Ameliorates Autism-like Symptoms Through Suppression of Th17 Related Signaling and Rectification of Oxidant-antioxidant Imbalance in Periphery and Brain of BTBR T+tf/J Mice. Behav Brain Res. 2019 05 17;364:213-224. PubMed PMID: 30790585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice. AU - Nadeem,Ahmed, AU - Ahmad,Sheikh F, AU - Al-Harbi,Naif O, AU - Attia,Sabry M, AU - Bakheet,Saleh A, AU - Ibrahim,Khalid E, AU - Alqahtani,Faleh, AU - Alqinyah,Mohammed, Y1 - 2019/02/19/ PY - 2018/11/21/received PY - 2019/02/17/revised PY - 2019/02/17/accepted PY - 2019/2/23/pubmed PY - 2019/2/23/medline PY - 2019/2/22/entrez KW - BTBR mice KW - Cerebellum KW - Neutrophils KW - Nuclear factor erythroid 2 related factor KW - Sulforaphane KW - Th17 cells SP - 213 EP - 224 JF - Behavioural brain research JO - Behav. Brain Res. VL - 364 N2 - Autism is a neurodevelopmental disease which is characterized by its core behavioral symptoms such as impairment in social interaction and stereotyped repetitive behavior. Th17 immune responses and oxidative stress are reported to be elevated in both human autistic subjects and BTBR T + Itpr3tf/J (BTBR) mice. On the other hand, activation of nuclear factor erythroid 2 related factor (Nrf2), a master transcription factor is essential for the management of anti-inflammatory and antioxidant genes. Sulforaphane activates Nrf2 and thus is considered a potential approach to treat several neurological disorders including autism. In the current work, we used sulforaphane in asocial BTBR mice and its social counterpart C57/BL6 (C57) mice to assess its therapeutic potential and molecular mechanisms (Th17 immune responses, and oxidant-antioxidant balance) through which it acts. Our results demonstrate that BTBR treated with sulforaphane had reduced self-grooming/marble burying behavior, and increased social interaction in three chambered sociability test as compared to untreated BTBR mice. Further, sulforaphane-treated BTBR mice had reduced Th17 immune responses (STAT3, RORC, IL-17 A and IL-23R expression in CD4 + T cells), oxidative stress parameters in neutrophils/cerebellum (NFkB, iNOS, and lipid peroxides). Furthermore, sulforaphane-treated BTBR and C57 mice had upregulated enzymatic antioxidant defenses in neutrophils/cerebellum (SOD, GPx and GR expression and activity). We reason that activation of Nrf2 by sulforaphane corrected Th17 immune dysfunction and oxidant-antioxidant imbalance in periphery and brain in BTBR mice. These mechanisms lead to improvement in autism-like symptoms in BTBR mice. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/30790585/Nrf2_activator_sulforaphane_ameliorates_autism_like_symptoms_through_suppression_of_Th17_related_signaling_and_rectification_of_oxidant_antioxidant_imbalance_in_periphery_and_brain_of_BTBR_T+tf/J_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(18)31635-8 DB - PRIME DP - Unbound Medicine ER -