title: Streptozotocin diabetic mice display depressive-like behavior and alterations in the structure, neurotransmission and plasticity of medial prefrontal cortex interneurons.
abstract: Diabetes mellitus patients are at increased risk of developing depression, although the neurobiological bases of this comorbidity are not yet fully understood. These patients show CNS alterations, similar to those found in major depression, including changes in the structure and neurotransmission of excitatory neurons. However, although depressive patients and animal models also display alterations in inhibitory networks, little is known about the effects of diabetes on interneurons. Our main objective was to study the impact of diabetes on interneurons of the medial prefrontal cortex (mPFC), one of the regions most affected by major depression. For this purpose we have induced diabetes with high-dose streptozotozin in transgenic mice displaying fluorescent interneurons. These animals showed a depressive-like behavior (increased immobility time in tail suspension test) in parallel with reductions in interneuronal dendritic arborization and in the expression of GAD67, the enzyme that synthetizes the inhibitory neurotransmitter GABA. However, the levels of PSA-NCAM, a plasticity-related molecule exclusively expressed by interneurons in the mPFC, were unaltered in the different regions and layers of this cortical area. Interestingly, diabetic mice also showed increased levels of synaptophysin, a synaptic vesicle protein. These results indicate that the structure and neurotransmission of interneurons is altered in the mPFC of diabetic mice and suggest that these changes may play a key role in the depressive symptoms associated to diabetes.
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Castillo-Gómez
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Simona
authors.initials: S
authors.lastname: Coviello
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Perez-Rando
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Curto
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Carceller
authors.affiliation: VLC Campus Research Microcluster "Technologies of Information and Control Applied to the Patophysiology and Treatment of Diabetes", Spain; Department of Psychobiology, University of Valencia, Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain; CIBERSAM: Spanish National Network for Research in Mental Health, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Spain; VLC Campus Research Microcluster "Technologies of Information and Control Applied to the Patophysiology and Treatment of Diabetes", Spain. Electronic address: nacher@uv.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Nacher
mesh_terms: D000818:Animals; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000473:pathology / Q000502:physiology*; D008297:Male; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D012794:Sialic Acids / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; D016708:Synaptophysin; C569015:Syp protein, mouse; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Depression; Diabetes; Interneuron; Stress; Structural plasticity