Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior

Betina Elfving; Heidi Kaastrup Müller; Ignasi Oliveras; Tina Becher Østerbøg; Cristobal Rio-Alamos; Ana Sanchez-Gonzalez; Adolf Tobeña; Alberto Fernandez-Teruel; Susana Aznar

doi:10.1016/j.pnpbp.2019.109669

Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior

Betina Elfving, Heidi Kaastrup Müller, Ignasi Oliveras, Tina Becher Østerbøg, Cristobal Rio-Alamos, Ana Sanchez-Gonzalez, Adolf Tobeña, Alberto Fernandez-Teruel, Susana Aznar^*

^*Corresponding author for this work

Department of Clinical Medicine - Translational Neuropsychiatry Unit

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

32 Citations (Scopus)

Abstract

Schizophrenia is considered a neurodevelopmental disorder. Recent reports relate synaptic alterations with disease etiology. The inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rat strains are a congenital neurobehavioral model, with the RHA-I displaying schizophrenia-related behaviors and serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptor alterations in the prefrontal cortex (PFC). We performed a comprehensive characterization of the RHA-I/RLA-I rats by real-time qPCR and Western blotting for 5-HT1A, 5-HT2A, mGlu2, dopamine 1 and dopamine 2 receptors (DRD1 and DRD2), AMPA receptor subunits Gria1, Gria2 and NMDA receptor subunits Grin1, Grin2a and Grin2b, as well as pre- and post-synaptic components in PFC and hippocampus (HIP). Besides corroborating decreased mGlu2 (Grm2) expression, we found increased mRNA levels for Snap25, Synaptophysin (Syp), Homer1 and Neuregulin-1 (Nrg1) in the PFC of the RHA-I and decreased expression of Vamp1, and Snapin in the HIP. We also showed alterations in Vamp1, Grin2b, Syp, Snap25 and Nrg1 at protein levels. mRNA levels of Brain Derived Neurotrophic Factor (BDNF) were increased in the PFC of the RHA-I rats, with no differences in the HIP, while BDNF protein levels were decreased in PFC and increased in HIP. To investigate the temporal dynamics of these synaptic markers during neurodevelopment, we made use of the open source BrainCloud™ dataset, and found that SYP, GRIN2B, NRG1, HOMER1, DRD1 and BDNF expression is upregulated in PFC during childhood and adolescence, suggesting a more immature neurobiological endophenotype in the RHA-I strain.

Original language	English
Article number	109669
Journal	Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume	95
Number of pages	12
ISSN	0278-5846
DOIs	https://doi.org/10.1016/j.pnpbp.2019.109669
Publication status	Published - Dec 2019

Keywords

Behavioral traits
Congenital animal model
Gene expression
Schizophrenia
Synaptic markers

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10.1016/j.pnpbp.2019.109669

Cite this

Elfving, B., Müller, H. K., Oliveras, I., Østerbøg, T. B., Rio-Alamos, C., Sanchez-Gonzalez, A., Tobeña, A., Fernandez-Teruel, A., & Aznar, S. (2019). Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 95, Article 109669. https://doi.org/10.1016/j.pnpbp.2019.109669

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title = "Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior",

abstract = "Schizophrenia is considered a neurodevelopmental disorder. Recent reports relate synaptic alterations with disease etiology. The inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rat strains are a congenital neurobehavioral model, with the RHA-I displaying schizophrenia-related behaviors and serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptor alterations in the prefrontal cortex (PFC). We performed a comprehensive characterization of the RHA-I/RLA-I rats by real-time qPCR and Western blotting for 5-HT1A, 5-HT2A, mGlu2, dopamine 1 and dopamine 2 receptors (DRD1 and DRD2), AMPA receptor subunits Gria1, Gria2 and NMDA receptor subunits Grin1, Grin2a and Grin2b, as well as pre- and post-synaptic components in PFC and hippocampus (HIP). Besides corroborating decreased mGlu2 (Grm2) expression, we found increased mRNA levels for Snap25, Synaptophysin (Syp), Homer1 and Neuregulin-1 (Nrg1) in the PFC of the RHA-I and decreased expression of Vamp1, and Snapin in the HIP. We also showed alterations in Vamp1, Grin2b, Syp, Snap25 and Nrg1 at protein levels. mRNA levels of Brain Derived Neurotrophic Factor (BDNF) were increased in the PFC of the RHA-I rats, with no differences in the HIP, while BDNF protein levels were decreased in PFC and increased in HIP. To investigate the temporal dynamics of these synaptic markers during neurodevelopment, we made use of the open source BrainCloud{\texttrademark} dataset, and found that SYP, GRIN2B, NRG1, HOMER1, DRD1 and BDNF expression is upregulated in PFC during childhood and adolescence, suggesting a more immature neurobiological endophenotype in the RHA-I strain.",

keywords = "Behavioral traits, Congenital animal model, Gene expression, Schizophrenia, Synaptic markers",

author = "Betina Elfving and M{\"u}ller, {Heidi Kaastrup} and Ignasi Oliveras and {\O}sterb{\o}g, {Tina Becher} and Cristobal Rio-Alamos and Ana Sanchez-Gonzalez and Adolf Tobe{\~n}a and Alberto Fernandez-Teruel and Susana Aznar",

year = "2019",

month = dec,

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language = "English",

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Elfving, B , Müller, HK, Oliveras, I, Østerbøg, TB, Rio-Alamos, C, Sanchez-Gonzalez, A, Tobeña, A, Fernandez-Teruel, A & Aznar, S 2019, 'Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 95, 109669. https://doi.org/10.1016/j.pnpbp.2019.109669

Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior. / Elfving, Betina ; Müller, Heidi Kaastrup; Oliveras, Ignasi et al.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 95, 109669, 12.2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior

AU - Elfving, Betina

AU - Müller, Heidi Kaastrup

AU - Oliveras, Ignasi

AU - Østerbøg, Tina Becher

AU - Rio-Alamos, Cristobal

AU - Sanchez-Gonzalez, Ana

AU - Tobeña, Adolf

AU - Fernandez-Teruel, Alberto

AU - Aznar, Susana

PY - 2019/12

Y1 - 2019/12

N2 - Schizophrenia is considered a neurodevelopmental disorder. Recent reports relate synaptic alterations with disease etiology. The inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rat strains are a congenital neurobehavioral model, with the RHA-I displaying schizophrenia-related behaviors and serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptor alterations in the prefrontal cortex (PFC). We performed a comprehensive characterization of the RHA-I/RLA-I rats by real-time qPCR and Western blotting for 5-HT1A, 5-HT2A, mGlu2, dopamine 1 and dopamine 2 receptors (DRD1 and DRD2), AMPA receptor subunits Gria1, Gria2 and NMDA receptor subunits Grin1, Grin2a and Grin2b, as well as pre- and post-synaptic components in PFC and hippocampus (HIP). Besides corroborating decreased mGlu2 (Grm2) expression, we found increased mRNA levels for Snap25, Synaptophysin (Syp), Homer1 and Neuregulin-1 (Nrg1) in the PFC of the RHA-I and decreased expression of Vamp1, and Snapin in the HIP. We also showed alterations in Vamp1, Grin2b, Syp, Snap25 and Nrg1 at protein levels. mRNA levels of Brain Derived Neurotrophic Factor (BDNF) were increased in the PFC of the RHA-I rats, with no differences in the HIP, while BDNF protein levels were decreased in PFC and increased in HIP. To investigate the temporal dynamics of these synaptic markers during neurodevelopment, we made use of the open source BrainCloud™ dataset, and found that SYP, GRIN2B, NRG1, HOMER1, DRD1 and BDNF expression is upregulated in PFC during childhood and adolescence, suggesting a more immature neurobiological endophenotype in the RHA-I strain.

AB - Schizophrenia is considered a neurodevelopmental disorder. Recent reports relate synaptic alterations with disease etiology. The inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rat strains are a congenital neurobehavioral model, with the RHA-I displaying schizophrenia-related behaviors and serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptor alterations in the prefrontal cortex (PFC). We performed a comprehensive characterization of the RHA-I/RLA-I rats by real-time qPCR and Western blotting for 5-HT1A, 5-HT2A, mGlu2, dopamine 1 and dopamine 2 receptors (DRD1 and DRD2), AMPA receptor subunits Gria1, Gria2 and NMDA receptor subunits Grin1, Grin2a and Grin2b, as well as pre- and post-synaptic components in PFC and hippocampus (HIP). Besides corroborating decreased mGlu2 (Grm2) expression, we found increased mRNA levels for Snap25, Synaptophysin (Syp), Homer1 and Neuregulin-1 (Nrg1) in the PFC of the RHA-I and decreased expression of Vamp1, and Snapin in the HIP. We also showed alterations in Vamp1, Grin2b, Syp, Snap25 and Nrg1 at protein levels. mRNA levels of Brain Derived Neurotrophic Factor (BDNF) were increased in the PFC of the RHA-I rats, with no differences in the HIP, while BDNF protein levels were decreased in PFC and increased in HIP. To investigate the temporal dynamics of these synaptic markers during neurodevelopment, we made use of the open source BrainCloud™ dataset, and found that SYP, GRIN2B, NRG1, HOMER1, DRD1 and BDNF expression is upregulated in PFC during childhood and adolescence, suggesting a more immature neurobiological endophenotype in the RHA-I strain.

KW - Behavioral traits

KW - Congenital animal model

KW - Gene expression

KW - Schizophrenia

KW - Synaptic markers

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U2 - 10.1016/j.pnpbp.2019.109669

DO - 10.1016/j.pnpbp.2019.109669

M3 - Journal article

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AN - SCOPUS:85067644430

SN - 0278-5846

VL - 95

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

M1 - 109669

ER -

Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior

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