Experimental Studies Indicate That ST-2223, the Antagonist of Histamine H3 and Dopamine D2/D3 Receptors, Restores Social Deficits and Neurotransmission Dysregulation in Mouse Model of Autism
| dc.contributor.author | Eissa, Nermin | |
| dc.contributor.author | Venkatachalam, Karthikkumar | |
| dc.contributor.author | Jayaprakash, Petrilla | |
| dc.contributor.author | Yuvaraju, Priya | |
| dc.contributor.author | Sadek, Bassem | |
| dc.contributor.author | ETAL.. | |
| dc.date.accessioned | 2024-05-30T10:14:54Z | |
| dc.date.available | 2024-05-30T10:14:54Z | |
| dc.date.issued | 2022-07-27 | |
| dc.description | The normal development of the brain memory, behavior regulation, and motor activity involve the crucial role of neurotransmitters that interconnect neurons [1]. Evidence suggests that the dysfunction of the neurotransmitter system by affecting neuronal cell migration, differentiation and synaptogenesis, and eventually developmental processes of the brain are thought to be the cause or precocious biomarkers of autism spectrum disorder (ASD) [2,3]. The neuropsychiatric developmental disorder ASD is characterized by social avoidance and lack of interest in social interactions. Deficits in these social domains can affect a child’s ability to function typically, which negatively affects the overall quality of life. Understanding the underlying mechanisms contributing to social deficits in ASD may help inform evidenced-based intervention strategies that may improve the social acceptability of ASD [4], and other dysregulated social interaction-associated disorders. | |
| dc.description.abstract | Altered regulation of neurotransmitters may lead to many pathophysiological changes in brain disorders including autism spectrum disorder (ASD). Given the fact that there are no FDA-approved effective treatments for the social deficits in ASD, the present study determined the effects of chronic systemic treatment of the novel multiple-active H3R/D2R/D3R receptor antagonist ST-2223 on ASD-related social deficits in a male Black and Tan Brachyury (BTBR) mice. ST-2223 (2.5, 5, and 10 mg/kg, i.p.) significantly and dose-dependently mitigated social deficits and disturbed anxiety levels of BTBR mice (p < 0.05) in comparison to the effects of aripiprazole (1 mg/kg, i.p.). Moreover, levels of monoaminergic neurotransmitters quantified by LC-MS/MS in four brain regions including the prefrontal cortex, cerebellum, striatum, and hippocampus unveiled significant elevation of histamine (HA) in the cerebellum and striatum; dopamine (DA) in the prefrontal cortex and striatum; as well as acetylcholine (ACh) in the prefrontal cortex, striatum, and hippocampus following ST-2223 (5 mg/kg) administration (all p < 0.05). These in vivo findings demonstrate the mitigating effects of a multiple-active H3R/D2R/D3R antagonist on social deficits of assessed BTBR mice, signifying its pharmacological potential to rescue core ASD-related behaviors and altered monoaminergic neurotransmitters. Further studies on neurochemical alterations in ASD are crucial to elucidate the early neurodevelopmental variations behind the core symptoms and heterogeneity of ASD, leading to new approaches for the future therapeutic management of ASD. Keywords: social deficits; neurotransmitters; histamine H3R antagonist; dopamine D2R/D3R antagonist; aripiprazole; autism | |
| dc.identifier.citation | Eissa, N., Venkatachalam, K., Jayaprakash, P., Yuvaraju, P., Falkenstein, M., Stark, H., & Sadek, B. (2022). Experimental Studies Indicate That ST-2223, the Antagonist of Histamine H3 and Dopamine D2/D3 Receptors, Restores Social Deficits and Neurotransmission Dysregulation in Mouse Model of Autism. Pharmaceuticals, 15(8), 929. | |
| dc.identifier.doi | https://doi.org/10.3390/ph15080929 | |
| dc.identifier.uri | https://dspace.adu.ac.ae/handle/1/5531 | |
| dc.language.iso | en | |
| dc.publisher | MDPI | |
| dc.title | Experimental Studies Indicate That ST-2223, the Antagonist of Histamine H3 and Dopamine D2/D3 Receptors, Restores Social Deficits and Neurotransmission Dysregulation in Mouse Model of Autism | |
| dc.type | Article |