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Title: BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment
Author(s): Harb, Mahmoud
Jagusch, Justina
Durairaja, Archana
Endres, ThomasLook up in the Integrated Authority File of the German National Library
Leßmann, VolkmarLook up in the Integrated Authority File of the German National Library
Fendt, MarkusLook up in the Integrated Authority File of the German National Library
Issue Date: 2021
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-1037543
Subjects: Schizophrenia
Brain-derived neurotrophic factor (BDNF)
Abstract: Brain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.
Open Access: Open access publication
License: (CC BY-SA 4.0) Creative Commons Attribution ShareAlike 4.0(CC BY-SA 4.0) Creative Commons Attribution ShareAlike 4.0
Sponsor/Funder: Projekt DEAL 2021
Journal Title: Translational Psychiatry
Publisher: Nature Publishing Group
Publisher Place: London
Volume: 11
Original Publication: 10.1038/s41398-021-01365-z
Page Start: 1
Page End: 13
Appears in Collections:Medizinische Fakultät (OA)

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