Genetic redox dysregulation induces behavioural deficits in the adult mouse: an animal model for schizophrenia

Détails

ID Serval
serval:BIB_4D7A35E417E8
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Genetic redox dysregulation induces behavioural deficits in the adult mouse: an animal model for schizophrenia
Titre de la conférence
Annual Conference of the Swiss Society of Sleep Research, Sleep Medicine and Chronobiology (SSSSC) and the Swiss Society of Biological Psychiatry (SSBP), Bern, March 25 and 26, 2009
Auteur(s)
Frank A., Dalton T., Chen Y., Cuenod M., Do K.Q.
ISBN
0302-282X
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
59
Série
Neuropsychobiology
Pages
61
Langue
anglais
Résumé
Background:
Glutathione (GSH), a major cellular redox regulator and antioxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse as model system with 60% decreased brain GSH levels and, thus, strong vulnerability to oxidative stress, we have shown that GSH dysregulation results in abnormal mouse brain morphology (e.g., reduced parvalbumin, PV, immuno-reactivity in frontal areas) and function. Additional oxidative stress, induced by GBR12909 (a dopamine re-uptake inhibitor), enhances morphological changes even further.
Aim:
In the present study we use the GCLM KO mouse model system, asking now, whether GSH dysregulation also compromises mouse behaviour and cognition.
Methods:
Male and female wildtype (WT) and GCLM-KO mice are treated with GBR12909 or phosphate buffered saline (PBS) from postnatal day (P) 5 to 10, and are behaviourally tested at P 60 and older.
Results:
In comparison to WT, KO animals of both sexes are hyperactive in the open field, display more frequent open arm entries on the elevated plus maze, longer float latencies in the Porsolt swim test, and more frequent contacts of novel and familiar objects. Contrary to other reports of animal models with reduced PV immuno-reactivity, GCLM-KO mice display normal rule learning capacity and perform normally on a spatial recognition task. GCLM-KO mice do, however, show a strong deficit in object-recognition after a 15 minutes retention delay. GBR12909 treatment exerts no additional effect.
Conclusions:
The results suggest that animals with impaired regulation of brain oxidative stress are impulsive and have reduced behavioural control in novel, unpredictable contexts. Moreover, GSH dysregulation seems to induce a selective attentional or stimulus-encoding deficit: despite intensive object exploration, GCLM-KO mice cannot discriminate between novel and familiar objects. In conclusion, the present data indicate that GSH dysregulation may contribute to the manifestation of behavioural and cognitive anomalies that are associated with schizophrenia.
Open Access
Oui
Création de la notice
19/02/2010 11:23
Dernière modification de la notice
20/08/2019 14:02
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