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PMID: 33485732 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Increased thin-spine density in frontal cortex pyramidal neurons in a genetic rat model of schizophrenia-relevant features.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology ·Vol. 44 ·2021-00-00 ·Pages 79-91

Sánchez-González A, Thougaard E, Tapias-Espinosa C, Cañete T, Sampedro-Viana D, Saunders JM, Toneatti R, Tobeña A, Gónzalez-Maeso J, Aznar S, Fernández-Teruel A

Abstract

The cellular mechanisms altered during brain wiring leading to cognitive disturbances in neurodevelopmental disorders remain unknown. We have previously reported altered cortical expression of neurodevelopmentally regulated synaptic markers in a genetic animal model of schizophrenia-relevant behavioral features, the Roman-High Avoidance rat strain (RHA-I). To further explore this phenotype, we looked at dendritic spines in cortical pyramidal neurons, as changes in spine density and morphology are one of the main processes taking place during adolescence. An HSV-viral vector carrying green fluorescent protein (GFP) was injected into the frontal cortex (FC) of a group of 11 RHA-I and 12 Roman-Low Avoidance (RLA-I) male rats. GFP labeled dendrites from pyramidal cells were 3D reconstructed and number and types of spines quantified. We observed an increased spine density in the RHA-I, corresponding to a larger fraction of immature thin spines, with no differences in stubby and mushroom spines. Glia cells, parvalbumin (PV) and somatostatin (SST) interneurons and surrounding perineuronal net (PNN) density are known to participate in FC and pyramidal neuron dendritic spine maturation. We determined by stereological-based quantification a significantly higher number of GFAP-positive astrocytes in the FC of the RHA-I strain, with no difference in microglia (Iba1-positive cells). The number of inhibitory PV, SST interneurons or PNN density, on the contrary, was unchanged. Results support our belief that the RHA-I strain presents a more immature FC, with some structural features like those observed during adolescence, adding construct validity to this strain as a genetic behavioral model of neurodevelopmental disorders.

Keywords
Behavioral animal models Brain development Neurodevelopmental disorders Prefrontal cortex Schizophrenia Synaptic maturation
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Sánchez-González A
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Thougaard E
Research Laboratory for Stereology and Neuroscience, Bispebjerg Copenhagen University Hospital, 2400 Copenhagen, Denmark.
Tapias-Espinosa C
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Cañete T
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Sampedro-Viana D
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Saunders J M
Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Toneatti R
Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Tobeña A
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Gónzalez-Maeso J
Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Aznar S
Research Laboratory for Stereology and Neuroscience, Bispebjerg Copenhagen University Hospital, 2400 Copenhagen, Denmark; Copenhagen Center for Translational Research, Bispebjerg Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: [email protected].
Fernández-Teruel A
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. Electronic address: [email protected].
Conflict of Interest

Conflict of interest We have no conflict of interest to declare.

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Article Info
Journal
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
Abbr.
Eur Neuropsychopharmacol
ISSN
1873-7862
DOI
10.1016/j.euroneuro.2021.01.006
Email
[email protected]
[email protected]
Published
2021-00-00
Epub
2021-00-21
Pages
79-91
Language
English
Region
Netherlands
NLM ID
9111390
PMCID
PMC7902438
Subset
IM
Grants
NIMH NIH HHS · F30 MH116550 · United States
NIDA NIH HHS · P30 DA033934 · United States
NIMH NIH HHS · R01 MH084894 · United States
NIMH NIH HHS · R01 MH111940 · United States
External Links
PubMed source DOI: 10.1016/j.euroneuro.2021.01.006 PMC Full Text View journal details
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