The histamine H3R and dopamine D2R/D3R antagonist ST-713 ameliorates autism-like behavioral features in BTBR T+tf/J mice by multiple actions

Venkatachalam, Karthikkumar; Eissa, Nermin; Awad, M.; Jayaprakash, Petrilla; Zhong, Sicheng; Stölting, Frauke; Stark, Holger; Sadek, Bassem

doi:10.1016/j.biopha.2021.111517

Cited by 20 publications

(18 citation statements)

References 72 publications

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“…Contrary, CUR (25, 50, and 100 mg/kg) were capable of restoring the levels of CAT levels in the cerebellum, but failed to alter the levels of SOD in the hippocampus. The results observed on the levels of oxidative stress markers are in harmony with numerous previous preclinical reports from our group and other research groups that investigated the effects of synthetic ligands modulating brain ACh levels on oxidative stress in the brains of different rodent models [ 53 , 54 , 55 , 56 , 57 ]. Also, the results observed for CUR are in harmony with a previous preclinical study in which CUR was found to mitigate the disturbed levels of IFN-γ, serotonin, glutamine, reduced glutathione, glutathione S -transferase, lipid peroxidase with an increase in CYP450, IL-6, glutamate, and oxidized glutathione in valproate-induced ASD in rats [ 58 ].…”

Section: Discussionsupporting

confidence: 89%

“…injections of MLA (1 µg/kg). Doses of CUR, DOZ, and MLA were selected according to previous experimental protocols C57 mice as well as BTBR mice [ 10 , 38 , 48 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. In these studies, a dose range of 15–125 mg/kg was used to assess several in vivo effects of CUR in mice.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, and in numerous previous studies from our group, DOZ (1 mg/kg, i.p.) was proven to show enhancing effects of cognitive functions of BTBR mice [ 9 , 10 , 48 , 53 , 55 , 56 , 57 ]. Therefore, a dose of 1 mg/kg of DOZ was selected in the current in vivo behavioral assessments.…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the effect of ST-713 on locomotion and anxiety behaviors in animals, an open field test (OFT) test was carried out. In addition to locomotor activity, the OFT is usually used to measure anxiety-like behaviors in experimental rodents [ 53 , 57 , 63 ]. The test provides a unique opportunity to systematically assess novel environment exploration, general locomotor activity, and provide an initial screen for anxiety-related behavior in experimental rodents.…”

Section: Methodsmentioning

confidence: 99%

“…Three Chamber Paradigm (TCP) TC test was performed according to previously described protocols [48,53,56,57,62,63]. Briefly, the cage consisted of three chambers, wherein the center chamber had two square shaped openings with doors, which provided access to left and right chambers.…”

Section: Behavioral Testsmentioning

confidence: 99%

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Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

Jayaprakash

Isaev

Shabbir

et al. 2021

IJMS

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Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

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