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Open AccessArticle
Alleviation of Autophagic Deficits and Neuroinflammation by Histamine H3 Receptor Antagonist E159 Ameliorates Autism-Related Behaviors in BTBR Mice
by
Shilu Deepa Thomas
Shilu Deepa Thomas 1,2,
Petrilla Jayaprakash
Petrilla Jayaprakash 1,2,
Nurfirzana Z. H. J. Marwan
Nurfirzana Z. H. J. Marwan 1,2,
Ezzatul A. B. A. Aziz
Ezzatul A. B. A. Aziz 1,2,
Kamil Kuder
Kamil Kuder 3,
Dorota Łażewska
Dorota Łażewska 3,
Katarzyna Kieć-Kononowicz
Katarzyna Kieć-Kononowicz 3 and
Bassem Sadek
Bassem Sadek
Prof. Bassem Sadek joined the Department of Pharmacology and Therapeutics, CMHS, UAEU in 2011 as an [...]
Prof. Bassem Sadek joined the Department of Pharmacology and Therapeutics, CMHS, UAEU in 2011 as an Assistant Professor of Pharmacology. He was promoted to Associate Professor in 2015, and then to Full Professor in 2021. He also holds a Research Associate position with the Heinrich Heine University of Düsseldorf, Federal Republic of Germany. He received his Bachelor of Pharmacy in 1994 from The Free University of Berlin (FUB), Germany, and PhD in Drug Design and Preclinical Drug Development in 1999 from FUB University (Germany). He was a Lecturer in Drug Design and Development (1999-2001). He was active in the research area of developing ligands targeting histamine H1-H3 receptors in the laboratory of Prof. Dr. Dr. h.c. Walter Schunack at the Institute of Pharmacy of FUB, Berlin, Germany. He then was appointed as an Assistant Professor at the AUST University, UAE, where he was active in teaching medicinal and pharmacological aspects of drugs to undergraduate students of Pharmacy and Dentistry. His research interests include preclinical drug development, behavioral neuropharmacology, and neuroscience.
1,2,*
1
Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates
2
Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
3
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna Str 9, 30-688 Kraków, Poland
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2024, 17(10), 1293; https://doi.org/10.3390/ph17101293 (registering DOI)
Submission received: 9 August 2024
/
Revised: 25 September 2024
/
Accepted: 26 September 2024
/
Published: 28 September 2024
Abstract
Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social interaction difficulties, repetitive behaviors, and immune dysregulation with elevated pro-inflammatory markers. Autophagic deficiency also contributes to social behavior deficits in ASD. Histamine H3 receptor (H3R) antagonism is a potential treatment strategy for brain disorders with features overlapping ASD, such as schizophrenia and Alzheimer’s disease. Methods: This study investigated the effects of sub-chronic systemic treatment with the H3R antagonist E159 on social deficits, repetitive behaviors, neuroinflammation, and autophagic disruption in male BTBR mice. Results: E159 (2.5, 5, and 10 mg/kg, i.p.) improved stereotypic repetitive behavior by reducing self-grooming time and enhancing spontaneous alternation in addition to attenuating social deficits. It also decreased pro-inflammatory cytokines in the cerebellum and hippocampus of treated BTBR mice. In BTBR mice, reduced expression of autophagy-related proteins LC3A/B and Beclin 1 was observed, which was elevated following treatment with E159, attenuating the disruption in autophagy. The co-administration with the H3R agonist MHA (10 mg/kg, i.p.) reversed these effects, highlighting the role of histaminergic neurotransmission in observed behavioral improvements. Conclusions: These preliminary findings suggest the therapeutic potential of H3R antagonists in targeting neuroinflammation and autophagic disruption to improve ASD-like behaviors.
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MDPI and ACS Style
Thomas, S.D.; Jayaprakash, P.; Marwan, N.Z.H.J.; Aziz, E.A.B.A.; Kuder, K.; Łażewska, D.; Kieć-Kononowicz, K.; Sadek, B.
Alleviation of Autophagic Deficits and Neuroinflammation by Histamine H3 Receptor Antagonist E159 Ameliorates Autism-Related Behaviors in BTBR Mice. Pharmaceuticals 2024, 17, 1293.
https://doi.org/10.3390/ph17101293
AMA Style
Thomas SD, Jayaprakash P, Marwan NZHJ, Aziz EABA, Kuder K, Łażewska D, Kieć-Kononowicz K, Sadek B.
Alleviation of Autophagic Deficits and Neuroinflammation by Histamine H3 Receptor Antagonist E159 Ameliorates Autism-Related Behaviors in BTBR Mice. Pharmaceuticals. 2024; 17(10):1293.
https://doi.org/10.3390/ph17101293
Chicago/Turabian Style
Thomas, Shilu Deepa, Petrilla Jayaprakash, Nurfirzana Z. H. J. Marwan, Ezzatul A. B. A. Aziz, Kamil Kuder, Dorota Łażewska, Katarzyna Kieć-Kononowicz, and Bassem Sadek.
2024. "Alleviation of Autophagic Deficits and Neuroinflammation by Histamine H3 Receptor Antagonist E159 Ameliorates Autism-Related Behaviors in BTBR Mice" Pharmaceuticals 17, no. 10: 1293.
https://doi.org/10.3390/ph17101293
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