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CC BY-NC-ND 4.0 · Planta Medica International Open 2021; 8(03): e104-e113
DOI: 10.1055/a-1491-1866
Original Papers

Effects of Chronic Administration of P-Cymene in an Animal Model of LPS-Induced Autism

Rick Wilhiam de Camargo 
1   Behavioral Neuroscience Laboratory (LabNeC), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Marina Goulart da Silva
1   Behavioral Neuroscience Laboratory (LabNeC), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Guilherme Cabreira Daros
1   Behavioral Neuroscience Laboratory (LabNeC), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Fabiana Durante de Medeiros
2   Laboratory of Neurobiology of Inflammatory and Metabolic Processes (NeuroIMet), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Naiana da Rosa
2   Laboratory of Neurobiology of Inflammatory and Metabolic Processes (NeuroIMet), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Caroline Liana Menschhein Medeiros
1   Behavioral Neuroscience Laboratory (LabNeC), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Eduardo de Medeiros Peretti
2   Laboratory of Neurobiology of Inflammatory and Metabolic Processes (NeuroIMet), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Juliete Palandi
3   Laboratory of Neuropathology Experimentation (LEN), Graduate Program in Neurosciences, Center of Biological Sciences, Federal University of Santa Catarina, Santa Catarina, Brazil
,
Franciane Bobinski
4   Experimental Neuroscience Laboratory (LaNEx), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Jucélia Jeremias Fortunato
5   Medical School, University of Southern Santa Catarina, Santa Catarina, Brazil
,
Rafael Mariano de Bitencourt
1   Behavioral Neuroscience Laboratory (LabNeC), Graduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil
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Abstract

p-Cymene is a monoterpene found in over 100 plant species. It shows a range of biological activity, including anti-inflammatory and antimicrobial effects. It is possibly a new therapeutic alternative for autism spectrum disorder characterized by deficits in interaction and behavioral abnormalities. These symptoms can occur in response to maternal immune activation through prenatal exposure to lipopolysaccharide. Thus, this study aimed to evaluate the behavioral, memory, and biochemical effects of chronic administration of p-cymene in an animal model of autism by prenatal maternal exposure to lipopolysaccharide. Twenty-four pregnant Wistar rats were used, who received 100 μg/kg of lipopolysaccharide or saline intraperitoneally (i.p.) on the 9.5 gestational day. After birth, the male offspring remained with the mothers until weaning and underwent model validation tests on postnatal day 30. From postnatal day 31 on, chronic administration, via i.p., of saline (1 mL/kg), risperidone (0.2 mg/kg), or p-cymene (100 mg/kg) for 22 days was performed. The animals were submitted to behavioral (postnatal day 52) and memory tests (postnatal days 52–53) and subsequently sacrificed (postnatal day 54) when their brain structures were removed for quantification of proinflammatory cytokines (TNF-α, interleukin 1β, and interleukin 6). Prenatal exposure to lipopolysaccharide significantly increased episodes of stereotyped movement (p=0.0001) and decreased parameters of social interaction in offspring, including sniffing, following, mounting, and allowing mounting (p=0.0043, p<0.0001, p=0.0009, and p=0.0200, respectively). Chronic p-cymene treatment was not significant for behavioral, memory, and biochemical tests. However, due to their pharmacokinetic characteristics, p-cymene nanomaterials’ formulation may be an exciting alternative to be tested for further results.

Key words

p-cymene - maternal immune activation - autism spectrum disorder - lipopolysaccharides - proinflammatory cytokines


Publication History

Received: 18 November 2020
Received: 30 March 2021

Accepted: 23 April 2021

Article published online:
11 August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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