Impaired vocal communication, sleep‐related discharges, and transient alteration of slow‐wave sleep in developing mice lacking the GluN2A subunit of N ‐methyl‐ d ‐aspartate receptors

Autor: Giuseppe Bertini, Rustem Khazipov, Vanessa Pauly, Nail Burnashev, Andrey Zakharov, Marat Minlebaev, Jérôme Epsztein, Séverine Corby-Pellegrino, Federico Del Gallo, Pierre-Pascal Lenck-Santini, Alexandre Pons-Bennaceur, Pierre Szepetowski, Pauline Perron, Laurent Aniksztejn, Manal Salmi
Přispěvatelé: pellegrino, Christophe, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kazan Federal University (KFU), Laboratory of Neurobiology, Kazan State University (KPFU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Università degli studi di Verona = University of Verona (UNIVR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), University of Verona (UNIVR)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Period (gene)
Local field potential
Electroencephalography
Sleep
Slow-Wave
Receptors
N-Methyl-D-Aspartate
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
medicine
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Receptor
Slow-wave sleep
Mice
Knockout
medicine.diagnostic_test
biology
musculoskeletal
neural
and ocular physiology
Sleep in non-human animals
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Neurology
Animals
Newborn
Cerebral cortex
biology.protein
GRIN2A
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurology (clinical)
Vocalization
Animal
Sleep
030217 neurology & neurosurgery
psychological phenomena and processes
Zdroj: Epilepsia
Epilepsia, Wiley, 2019, ⟨10.1111/epi.16060⟩
Epilepsia, 2019, ⟨10.1111/epi.16060⟩
ISSN: 0013-9580
DOI: 10.1111/epi.16060⟩
Popis: Objective Glutamate-gated N-methyl-d-aspartate receptors (NMDARs) are instrumental to brain development and functioning. Defects in the GRIN2A gene, encoding the GluN2A subunit of NMDARs, cause slow-wave sleep (SWS)-related disorders of the epilepsy-aphasia spectrum (EAS). The as-yet poorly understood developmental sequence of early EAS-related phenotypes, and the role of GluN2A-containing NMDARs in the development of SWS and associated electroencephalographic (EEG) activity patterns, were investigated in Grin2a knockout (KO) mice. Methods Early social communication was investigated by ultrasonic vocalization (USV) recordings; the relationship of electrical activity of the cerebral cortex with SWS was studied using deep local field potential or chronic EEG recordings at various postnatal stages. Results Grin2a KO pups displayed altered USV and increased occurrence of high-voltage spindles. The pattern of slow-wave activity induced by low-dose isoflurane was altered in Grin2a KO mice in the 3rd postnatal week and at 1 month of age. These alterations included strong suppression of the delta oscillation power and an increase in the occurrence of the spike-wave bursts. The proportion of SWS and the sleep quality were transiently reduced in Grin2a KO mice aged 1 month but recovered by the age of 2 months. Grin2a KO mice also displayed spontaneous spike-wave discharges, which occurred nearly exclusively during SWS, at 1 and 2 months of age. Significance The impaired vocal communication, the spike-wave discharges occurring almost exclusively in SWS, and the age-dependent alteration of SWS that were all seen in Grin2a KO mice matched the sleep-related and age-dependent manifestations seen in children with EAS, hence validating the Grin2a KO as a reliable model of EAS disorders. Our data also show that GluN2A-containing NMDARs are involved in slow-wave activity, and that the period of postnatal brain development (postnatal day 30) when several anomalies peaked might be critical for GluN2A-dependent, sleep-related physiological and pathological processes.
Databáze: OpenAIRE
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