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Neurochemical Research

, Volume 44, Issue 6, pp 1494–1507 | Cite as

Atypical Auditory Brainstem Response and Protein Expression Aberrations Related to ASD and Hearing Loss in the Adnp Haploinsufficient Mouse Brain

  • Gal Hacohen-Kleiman
  • Ofer Yizhar-Barnea
  • Olga Touloumi
  • Roza Lagoudaki
  • Karen B. Avraham
  • Nikolaos Grigoriadis
  • Illana GozesEmail author
Original Paper
  • 170 Downloads

Abstract

Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally. Respectively, mutations in the human ADNP gene (ADNP syndrome), cause multi-system body dysfunctions with apparent ASD-related traits, commencing as early as childhood. The Adnp haploinsufficient (Adnp+/−) mouse model was researched before in relations to Alzheimer’s disease and autism. Adnp+/− mice suffer from deficient social memory, vocal and motor impediments, irregular tooth eruption and short stature, all of which corresponds with reported phenotypes in patients with the ADNP syndrome. Recently, a more elaborated description of the ADNP syndrome was published, presenting impediments such as hearing disabilities in > 10% of the studied children. Irregular auditory brainstem response (ABR) has been connected to ASD-related cases and has been suggested as a potential hallmark for autism, allowing diagnosis of ASD risk and early intervention. Herein, we present detriment hearing in the Adnp+/− mice with atypical ABR and significant protein expression irregularities that coincides with ASD and hearing loss studies in the brain.

Keywords

Activity-dependent neuroprotective protein ADNP ADNP syndrome Hearing loss Developmental delays Auditory brainstem response ABR Adnp haploinsufficient Adnp+/− 

Notes

Acknowledgements

Illana Gozes laboratory is supported by the following grants, Israel Science Foundation (ISF) 1424/14, European Research Area Networks (ERA-NET) neuron AUTISYN, National Science Foundation (NSF) and US-Israel Binational Science Foundation (BSF) 2016746, AMN Foundation as well as Drs. Ronith and Armand Stemmer, Mr Arthur Gerbi (French Friends of Tel Aviv University), and Spanish Friends of Tel Aviv University. This study is in partial fulfillment graduate studies requirements for Gal Hacohen-Kleiman. Gal Hacohen-Kleiman is supported by Eshkol fellowships, the Israel Ministry of Science and Technology. We thank Evangelia Nousiopoulou for the technical support with the immunohistochemistry.

Compliance with Ethical Standards

Conflict of interest

Professor Illana Gozes is the Chief Scientific Officer of Coronis Neurosciences (http://www.coronisns.com/) developing NAP (CP201) for the ADNP syndrome.

Human and Animal Rights Statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Care and Use Committee of Tel Aviv University and the Israeli Ministry of Health (M-15-059).

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Lily and Avrahamo Gildor Chair for the Investigation of Growth Factors; The Elton Laboratory for Neuroendocrinology; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain StudiesTel Aviv UniversityTel AvivIsrael
  2. 2.Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of NeuroscienceTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Neurology, Laboratory of Experimental NeurologyAHEPA University Hospital, Aristotle University of ThessalonikiThessalonikiGreece

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