A Jacob/nsmf gene knockout does not protect against acute hypoxia- and NMDA-induced excitotoxic cell death

Molecular Brain

Micro Report

Anna Karpova¹  Guilherme M. Gomes¹  Michael R. Kreutz²  Julia Bär³ 

[1] Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany;Center for Behavioral Brain Sciences, Otto-Von-Guericke University, Magdeburg, Germany;Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany;Center for Behavioral Brain Sciences, Otto-Von-Guericke University, Magdeburg, Germany;Leibniz Group “Dendritic Organelles and Synaptic Function”, University Medical Center Hamburg-Eppendorf, Center for Molecular Neurobiology, ZMNH, Hamburg, Germany;German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany;Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany;Research Group Optobiology, Institute of Biology, HU Berlin, 10115, Berlin, Germany;

关键词: Jacob;    Nsmf;    Oxygen–glucose deprivation;    Cell death;    Excitoxicity;    Extrasynaptic N-methyl--aspartate receptor;    Stroke;   

DOI  :  10.1186/s13041-023-01012-2

 received in 2022-12-26, accepted in 2023-02-02,  发布年份 2023

来源: Springer

【 摘 要 】

Jacob is a synapto-nuclear messenger protein that encodes and transduces the origin of synaptic and extrasynaptic NMDA receptor signals to the nucleus. The protein assembles a signalosome that differs in case of synaptic or extrasynaptic NMDAR activation. Following nuclear import Jacob docks these signalosomes to the transcription factor CREB. We have recently shown that amyloid-β and extrasynaptic NMDAR activation triggers the translocation of a Jacob signalosome that results in inactivation of the transcription factor CREB, a phenomenon termed Jacob-induced CREB shut-off (JaCS). JaCS contributes to early Alzheimer’s disease pathology and the absence of Jacob protects against amyloid pathology. Given that extrasynaptic activity is also involved in acute excitotoxicity, like in stroke, we asked whether nsmf gene knockout will also protect against acute insults, like oxygen and glucose deprivation and excitotoxic NMDA stimulation. nsmf is the gene that encodes for the Jacob protein. Here we show that organotypic hippocampal slices from wild-type and nsmf−/− mice display similar degrees of degeneration when exposed to either oxygen glucose deprivation or 50 µM NMDAto induce excitotoxicity. This lack of neuroprotection indicates that JaCS is mainly relevant in conditions of low level chronic extrasynaptic NMDAR activation that results in cellular degeneration induced by alterations in gene transcription.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 1