Possible prevention or treatment of impairments induced by an early prenatal exposure to lipopolysaccharide in an experimental model of autism

• Grant number: 12/07007-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: May 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Luciano Freitas Felicio
• Grantee: Thiago Berti Kirsten
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/51886-3 - Neuroimmunomodulation: drugs, stress and cytokines on nervous, endocrine and immune systems relationships, AP.TEM

Abstract

Maternal immune activation during pregnancy has been associated with neuropsychiatric disorders. During the master's and doctor degree of the proponent (both with FAPESP grant) it was proposed that exposure to lipopolysaccharide (LPS), which mimics a bacterial infection (100 ug/kg, ip., on gestational day 9.5 of rats) would be an experimental model of autism, based on similar findings to those found in autistic patients: social, communicational and cognitional impairments, as well as repetitive behaviors and higher prevalence in males. Moreover, the model also revealed a reduction in striatal tyrosine hydroxylase (TH), dopamine (DA) and metabolites levels. It is intended now to administrate different interventions to possibly prevent or treat the impairments associated with autism in our model. The first intervention is still in gestation, after LPS exposure, with the administration of zinc, because the infection leads to maternal and fetal hypozincemia, also associated with offspring impairments. The second intervention is in the young offspring that received LPS during pregnancy, with the pioglitazone administration, which is classically used in the treatment of diabetes, but can also exert anti-inflammatory effect, and therefore was chosen as a candidate for the treatment of autism. To verify the success of the treatments, the reproductive parameters, ultrasonic vocalization, play behavior and striatal TH, DA and metabolites levels will be evaluated. These zinc and pioglitazone studies are very important, because there is currently no consensus regarding which interventions are most effective for autism and the existent medicaments are beneficial only for some symptoms and presents several side effects.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KIRSTEN, THIAGO B.; LIPPI, LUCIANA L.; BEVILACQUA, ESTELA; BERNARDI, MARIA M.. LPS Exposure Increases Maternal Corticosterone Levels, Causes Placental Injury and Increases IL-1B Levels in Adult Rat Offspring: Relevance to Autism. PLoS One, v. 8, n. 12, DEC 2 2013. (08/53861-5, 09/51886-3, 12/07007-8)

KIRSTEN, THIAGO B.; CASARIN, RENATO C.; BERNARDI, MARIA M.; FELICIO, LUCIANO F.. Pioglitazone abolishes cognition impairments as well as BDNF and neurotensin disturbances in a rat model of autism. BIOLOGY OPEN, v. 8, n. 5, MAY 2019. (12/07007-8)

KIRSTEN, THIAGO B.; BERNARDI, MARIA M.. Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies. Behavioural Brain Research, v. 331, p. 25-29, JUL 28 2017. (06/54587-9, 12/07007-8)

KIRSTEN, THIAGO BERTI; CHAVES-KIRSTEN, GABRIELA P.; BERNARDES, SUENE; SCAVONE, CRISTOFORO; SARKIS, JORGE E.; BERNARDI, MARIA MARTHA; FELICIO, LUCIANO F.. Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring. PLoS One, v. 10, n. 7, JUL 28 2015. (12/07007-8, 13/01610-7, 09/51886-3)

GALVAO, MARCELLA C.; CHAVES-KIRSTEN, GABRIELA P.; QUEIROZ-HAZARBASSANOV, NICOLLE; CARVALHO, VIRGINIA M.; BERNARDI, MARIA M.; KIRSTEN, THIAGO B.. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation. Life Sciences, v. 120, p. 54-60, JAN 1 2015. (12/07007-8)

KIRSTEN, THIAGO B.; GALVAO, MARCELLA C.; REIS-SILVA, THIAGO M.; QUEIROZ-HAZARBASSANOV, NICOLLE; BERNARDI, MARIA M.. Zinc Prevents Sickness Behavior Induced by Lipopolysaccharides after a Stress Challenge in Rats. PLoS One, v. 10, n. 3, MAR 16 2015. (12/07007-8, 09/51886-3)

KIRSTEN, THIAGO BERTI; CASARIN, RENATO C.; BERNARDI, MARIA M.; FELICIO, LUCIANO F.. Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway. PLoS One, v. 13, n. 5, MAY 23 2018. (12/07007-8)

KIRSTEN, THIAGO B.; QUEIROZ-HAZARBASSANOV, NICOLLE; BERNARDI, MARIA M.; FELICIO, LUCIANO F.. Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure. Life Sciences, v. 130, p. 12-17, JUN 1 2015. (12/07007-8, 09/51886-3)