Increased thin-spine density in frontal cortex pyramidal neurons in a genetic rat model of schizophrenia-relevant features
Sánchez González, Ana (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Thougaard, Estrid (Research Laboratory for Stereology and Neuroscience, Bispebjerg Copenhagen University Hospital)
Tapias-Espinosa, Carles (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Cañete, Toni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Sampedro-Viana, Daniel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Saunders, Justin M. (Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine)
Toneatti, Rudy (Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine)
Tobeña, Adolf 1950- (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Gonzalez-Maeso, Javier (Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine)
Aznar, Susana (Research Laboratory for Stereology and Neuroscience, Bispebjerg Copenhagen University Hospital)
Fernández-Teruel, Alberto (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Universitat Autònoma de Barcelona. Institut de Neurociències

Data:	2021
Resum:	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.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Schizophrenia ; Neurodevelopmental disorders ; Behavioral animal models ; Synaptic maturation ; Brain development ; Prefrontal cortex
Publicat a:	European neuropsychopharmacology, Vol. 44 (March 2021) , p. 79-91, ISSN 1873-7862

DOI: 10.1016/j.euroneuro.2021.01.006
PMID: 33485732

22 p, 475.4 KB

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