Cortical excitatory and inhibitory neuron deficits may underlie the cognitive and social impairments in a mouse model of schizophrenia with exonic Reln deletion
Rattachement africain : jp, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Reelin is an essential extracellular matrix glycoprotein involved in the formation of cortical layers and has been associated with several neuropsychiatric conditions, such as schizophrenia (SCZ). To explore its role in brain function and its potential involvement in SCZ, we developed a Reln heterozygous deletion ( Reln del/+ ) mouse model that mimics a genetic deletion observed in a Japanese patient with SCZ. In previous studies, we demonstrated that Reln del/+ mice exhibit cognitive impairments in a visual discrimination test. Here, we found that Reln del/+ mice displayed impairments in social novelty recognition, while social preference remained intact. Immunohistochemical analyses revealed a significant decrease in the numbers of calcium/calmodulin-dependent protein kinase II (CaMKII)-positive glutamatergic pyramidal neurons, gamma-aminobutyric acid (GABA)-ergic interneurons, and parvalbumin (PV)-positive interneurons in the medial prefrontal cortex (mPFC) of Reln del/+ mice. Furthermore, Reln del/+ mice exhibited significant deficits in excitatory spine density and morphology, as well as a decrease number of PV boutons in the mPFC compared to wild-type (WT) mice. Finally, we demonstrated that injection of AAV-R36-Myc virus into the mPFC can improve social novelty impairments in Reln del/+ mice, but no effects on WT control. These findings indicate that Reln del/+ mice could be a valuable model for exploring the neurobiological mechanisms underlying cognitive and social impairments in SCZ. Futhermore, our results with AAV-R36-Myc also suggest the therapeutic potential of Reelin replacement, warranting further investigation as a possible treatment strategy for SCZ. Highlights Reelin deficiency disrupts social novelty, but not social preference, in Reln del/+ mice Reln del/+ mice serve as a novel model to investigate impairments of neuronal mechanisms on schizophrenia AAV-R36-myc injection rescues social novelty deficits in Reln del/+ mice Reelin replacement therapy is a potential treatment for schizophrenia Graphical abstract
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Cortical excitatory and inhibitory neuron deficits may underlie the cognitive and social impairments in a mouse model of schizophrenia with exonic <i>Reln</i> deletion
- Date Crossref
- 25/07/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Aichi University pays non établi dans la noticeUniversité ou école supérieure
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Nagoya University Hospital Brain and Mind Research Center pays non établi dans la noticeÉtablissement de santé
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MIND Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Nagoya University Department of Neuropsychopharmacology and Hospital Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Fujita Health University International Center for Brain Science (ICBS) pays non établi dans la noticeUniversité ou école supérieure
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Aichi Institute of Technology pays non établi dans la noticeUniversité ou école supérieure
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Japanese Drug Organization of Appropriate Use and Research pays non établi dans la noticeOrganisation à but non lucratif
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Neurosciences Institute pays non établi dans la noticeOrganisation à but non lucratif
Aichi University, Brain and Mind Research Center — Nagoya University Hospital et MIND Research Institute, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.