loading page

Reelin cells and sex-dependent synaptopathology in autism following postnatal immune activation
  • +10
  • Maryam Ardalan,
  • Tetyana Chumak,
  • Alexandra Quist,
  • Eva Hermans,
  • Ali H.Rafati,
  • Giacomo Gravina,
  • Seyedeh Marziyeh Jabbari Shiadeh,
  • Pernilla Svedin,
  • Setareh Alabaf,
  • Brian Hansen,
  • Gregers Wegener,
  • Lars Westberg,
  • Carina Mallard
Maryam Ardalan
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg

Corresponding Author:[email protected]

Author Profile
Tetyana Chumak
University of Gothenburg
Author Profile
Alexandra Quist
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile
Eva Hermans
Utrecht University
Author Profile
Ali H.Rafati
Translational Neuropsychiatry Unit
Author Profile
Giacomo Gravina
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile
Seyedeh Marziyeh Jabbari Shiadeh
Ã…rhus Universitetshospital
Author Profile
Pernilla Svedin
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile
Setareh Alabaf
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile
Brian Hansen
Ã…rhus Universitetshospital
Author Profile
Gregers Wegener
Translational Neuropsychiatry Unit
Author Profile
Lars Westberg
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile
Carina Mallard
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg
Author Profile

Abstract

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behavior in males following PIA. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.
16 Jun 2021Submitted to British Journal of Pharmacology
13 Jul 2021Submission Checks Completed
13 Jul 2021Assigned to Editor
14 Jul 2021Reviewer(s) Assigned
27 Sep 2021Review(s) Completed, Editorial Evaluation Pending
07 Oct 2021Editorial Decision: Revise Minor
18 Jan 20221st Revision Received
24 Jan 2022Submission Checks Completed
24 Jan 2022Assigned to Editor
26 Jan 2022Reviewer(s) Assigned
14 Feb 2022Review(s) Completed, Editorial Evaluation Pending
21 Feb 2022Editorial Decision: Revise Minor
25 Feb 20222nd Revision Received
02 Mar 2022Submission Checks Completed
02 Mar 2022Assigned to Editor
04 Mar 2022Reviewer(s) Assigned
17 Mar 2022Review(s) Completed, Editorial Evaluation Pending
26 Mar 2022Editorial Decision: Revise Minor
28 Mar 20223rd Revision Received
29 Mar 2022Submission Checks Completed
29 Mar 2022Assigned to Editor
01 Apr 2022Editorial Decision: Revise Minor
07 Apr 20224th Revision Received
08 Apr 2022Submission Checks Completed
08 Apr 2022Assigned to Editor
10 Apr 2022Editorial Decision: Accept
Sep 2022Published in British Journal of Pharmacology volume 179 issue 17 on pages 4400-4422. 10.1111/bph.15859