Autistic-Like Behaviours and Associated Brain Structural Plasticity are Modulated by Oxytocin in Maternally Separated Rats

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Autistic-Like Behaviours and Associated Brain Structural Plasticity are Modulated by Oxytocin in Maternally Separated Rats. / Mansouri, Monireh; Pouretemad, Hamidreza; Roghani, Mehrdad; Wegener, Gregers; Ardalan, Maryam.

In: Behavioural Brain Research, Vol. 393, 112756, 2020.

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@article{60be52cbf8044eff86527163ebc44a55,
title = "Autistic-Like Behaviours and Associated Brain Structural Plasticity are Modulated by Oxytocin in Maternally Separated Rats",
abstract = "BACKGROUND: Early psycho-social experiences influence the developing brain and possible onset of various neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). ASD is characterized by a variety of brain abnormalities, including alteration of oxytocin receptors in the brain. Recently, early life adverse experiences, such as maternal separation (MS), have been shown to constitute risk factors for ASD in preclinical studies. Therefore, the main aims of the current study were to i) explore the association between onset of autistic-like behaviours and molecular/structural changes in the brain following MS, and ii) evaluate the possible beneficial effects of oxytocin treatment on the same parameters.METHOD AND MATERIAL: Male rats were exposed to the maternal separation from post-natal day (PND) 1 to PND14. After weaning, daily injections of oxytocin (1 mg/kg, ip) were administered (PND22-30), followed by examination of autism-related behaviours at adolescence (PND 42-50). Brain structural plasticity was examined using stereological methods, and the plasma level of brain derived neurotrophic factor (BDNF) was analysed using ELISA.RESULTS: We found that maternal separation induced autistic-like behaviours, which was associated with increase in the hippocampal CA1 stratum radiatum (CA1.SR) volume. In addition, we observed increase in the infralimbic brain region volume and in the number of the pyramidal neurons in the same brain region. Maternal separation significantly increased the plasma BDNF levels. Treatment with oxytocin improved autistic like behaviours, normalized the number of neurons and the volume of the infralimbic region as well as the plasma BDNF level (p < 0.05).CONCLUSION: Maternal separation induced autistic-like behaviours, brain structural impairment together with plasma BDNF level abnormality, which could be improved by oxytocin treatment.",
keywords = "Autism spectrum disorder, Maternal deprivation, Neural plasticity, Oxytocin",
author = "Monireh Mansouri and Hamidreza Pouretemad and Mehrdad Roghani and Gregers Wegener and Maryam Ardalan",
note = "Copyright {\textcopyright} 2020. Published by Elsevier B.V.",
year = "2020",
doi = "10.1016/j.bbr.2020.112756",
language = "English",
volume = "393",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Autistic-Like Behaviours and Associated Brain Structural Plasticity are Modulated by Oxytocin in Maternally Separated Rats

AU - Mansouri, Monireh

AU - Pouretemad, Hamidreza

AU - Roghani, Mehrdad

AU - Wegener, Gregers

AU - Ardalan, Maryam

N1 - Copyright © 2020. Published by Elsevier B.V.

PY - 2020

Y1 - 2020

N2 - BACKGROUND: Early psycho-social experiences influence the developing brain and possible onset of various neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). ASD is characterized by a variety of brain abnormalities, including alteration of oxytocin receptors in the brain. Recently, early life adverse experiences, such as maternal separation (MS), have been shown to constitute risk factors for ASD in preclinical studies. Therefore, the main aims of the current study were to i) explore the association between onset of autistic-like behaviours and molecular/structural changes in the brain following MS, and ii) evaluate the possible beneficial effects of oxytocin treatment on the same parameters.METHOD AND MATERIAL: Male rats were exposed to the maternal separation from post-natal day (PND) 1 to PND14. After weaning, daily injections of oxytocin (1 mg/kg, ip) were administered (PND22-30), followed by examination of autism-related behaviours at adolescence (PND 42-50). Brain structural plasticity was examined using stereological methods, and the plasma level of brain derived neurotrophic factor (BDNF) was analysed using ELISA.RESULTS: We found that maternal separation induced autistic-like behaviours, which was associated with increase in the hippocampal CA1 stratum radiatum (CA1.SR) volume. In addition, we observed increase in the infralimbic brain region volume and in the number of the pyramidal neurons in the same brain region. Maternal separation significantly increased the plasma BDNF levels. Treatment with oxytocin improved autistic like behaviours, normalized the number of neurons and the volume of the infralimbic region as well as the plasma BDNF level (p < 0.05).CONCLUSION: Maternal separation induced autistic-like behaviours, brain structural impairment together with plasma BDNF level abnormality, which could be improved by oxytocin treatment.

AB - BACKGROUND: Early psycho-social experiences influence the developing brain and possible onset of various neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). ASD is characterized by a variety of brain abnormalities, including alteration of oxytocin receptors in the brain. Recently, early life adverse experiences, such as maternal separation (MS), have been shown to constitute risk factors for ASD in preclinical studies. Therefore, the main aims of the current study were to i) explore the association between onset of autistic-like behaviours and molecular/structural changes in the brain following MS, and ii) evaluate the possible beneficial effects of oxytocin treatment on the same parameters.METHOD AND MATERIAL: Male rats were exposed to the maternal separation from post-natal day (PND) 1 to PND14. After weaning, daily injections of oxytocin (1 mg/kg, ip) were administered (PND22-30), followed by examination of autism-related behaviours at adolescence (PND 42-50). Brain structural plasticity was examined using stereological methods, and the plasma level of brain derived neurotrophic factor (BDNF) was analysed using ELISA.RESULTS: We found that maternal separation induced autistic-like behaviours, which was associated with increase in the hippocampal CA1 stratum radiatum (CA1.SR) volume. In addition, we observed increase in the infralimbic brain region volume and in the number of the pyramidal neurons in the same brain region. Maternal separation significantly increased the plasma BDNF levels. Treatment with oxytocin improved autistic like behaviours, normalized the number of neurons and the volume of the infralimbic region as well as the plasma BDNF level (p < 0.05).CONCLUSION: Maternal separation induced autistic-like behaviours, brain structural impairment together with plasma BDNF level abnormality, which could be improved by oxytocin treatment.

KW - Autism spectrum disorder

KW - Maternal deprivation

KW - Neural plasticity

KW - Oxytocin

UR - http://www.scopus.com/inward/record.url?scp=85086714296&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2020.112756

DO - 10.1016/j.bbr.2020.112756

M3 - Journal article

C2 - 32535183

VL - 393

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

M1 - 112756

ER -