Cognition- and circuit-based dysfunction in a mouse model of 22q11.2 microdeletion syndrome: effects of stress

Autor: Michael Didriksen, Anushree Tripathi, Arnaud Cressant, Thérèse M. Jay, Michael Spedding, Esther Schenker
Přispěvatelé: Martinez Rico, Clara, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Umeå University, Institut de Recherches SERVIER (IRS), Spedding Research Solutions SAS [Le Vesinet, France], H. Lundbeck A/S [Valby, Denmark], Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), France Brain@vior SAS [Saint-Prest, France], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
22q11 microdeletion
[SDV]Life Sciences [q-bio]
[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health
Hippocampus
Mice
0302 clinical medicine
Cognition
Genotype
Prefrontal cortex
Clozapine
0303 health sciences
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
Long-term potentiation
[SDV] Life Sciences [q-bio]
Psychiatry and Mental health
hippocampal-prefrontal synaptic plasticity
Neurovetenskaper
medicine.drug
medicine.medical_specialty
Prefrontal Cortex
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Predictive markers
Stress
Article
Learning and memory
lcsh:RC321-571
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Biological Psychiatry
030304 developmental biology
business.industry
animal model
Neurosciences
Mice
Inbred C57BL
Electrophysiology
Disease Models
Animal
Endocrinology
nervous system
[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health
Synaptic plasticity
biology.protein
Schizophrenia
business
030217 neurology & neurosurgery
Parvalbumin
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Translational Psychiatry
Translational Psychiatry, Nature Pub. Group, 2020, 10 (1), pp.41. ⟨10.1038/s41398-020-0687-z⟩
Translational Psychiatry, Vol 10, Iss 1, Pp 1-15 (2020)
ISSN: 2158-3188
DOI: 10.1038/s41398-020-0687-z⟩
Popis: Genetic microdeletion at the 22q11 locus is associated with very high risk for schizophrenia. The 22q11.2 microdeletion (Df(h22q11)/+) mouse model shows cognitive deficits observed in this disorder, some of which can be linked to dysfunction of the prefrontal cortex (PFC). We used behavioral (n = 10 per genotype), electrophysiological (n = 7 per genotype per group), and neuroanatomical (n = 5 per genotype) techniques to investigate schizophrenia-related pathology of Df(h22q11)/+ mice, which showed a significant decrease in the total number of parvalbumin positive interneurons in the medial PFC. The Df(h22q11)/+ mice when tested on PFC-dependent behavioral tasks, including gambling tasks, perform significantly worse than control animals while exhibiting normal behavior on hippocampus-dependent tasks. They also show a significant decrease in hippocampus-medial Prefrontal cortex (H-PFC) synaptic plasticity (long-term potentiation, LTP). Acute platform stress almost abolished H-PFC LTP in both wild-type and Df(h22q11)/+ mice. H-PFC LTP was restored to prestress levels by clozapine (3 mg/kg i.p.) in stressed Df(h22q11)/+ mice, but the restoration of stress-induced LTP, while significant, was similar between wild-type and Df(h22q11)/+ mice. A medial PFC dysfunction may underlie the negative and cognitive symptoms in human 22q11 deletion carriers, and these results are relevant to the current debate on the utility of clozapine in such subjects.
Databáze: OpenAIRE
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