c-Jun N-terminal Kinase 1 ablation protects against metabolic-induced hippocampal cognitive impairments
| Autor: | Gemma Casadesus, Oriol Busquets, Ester Verdaguer, Rubén Darío Castro-Torres, Àuria Eritja, Miren Ettcheto, Carme Auladell, Jordi Olloquequi, Antoni Camins, Jaume Folch, Carlos Beas-Zarate, Mònica Bulló, Triana Espinosa-Jiménez |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Dendritic spine Dendritic Spines Mice Transgenic Nerve Tissue Proteins Type 2 diabetes Hippocampal formation Diet High-Fat Hippocampus Memory and Learning Tests Neuroprotection Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Drug Discovery medicine Animals Cognitive Dysfunction Mitogen-Activated Protein Kinase 8 Genetics (clinical) Arc (protein) Kinase business.industry Brain-Derived Neurotrophic Factor Body Weight Microfilament Proteins c-jun medicine.disease Mitochondria Mice Inbred C57BL Diabetes Mellitus Type 2 Astrocytes Molecular Medicine Microglia Insulin Resistance biological phenomena cell phenomena and immunity business Neuroscience hormones hormone substitutes and hormone antagonists 030215 immunology |
| Zdroj: | Journal of Molecular Medicine. 97:1723-1733 |
| ISSN: | 1432-1440 0946-2716 |
| Popis: | The development of metabolic alterations like insulin resistance has been associated with dysfunctions in mitochondrial oxidative capacity, induction of neuroinflammatory responses, and the appearance of cognitive impairments in the brain. The c-Jun N-terminal Kinase 1 (JNK1) is a potential key modulator of these mechanisms. The current study identifies a protective effect of whole-body JNK1 knockout in the presence of a high-fat diet (HFD). Specifically, the data suggest that mice missing JNK1 show increased insulin sensitivity and mitochondrial activity, as well as reduced body weight, and astrocyte and microglial reactivity. Finally, these animals are also protected against HFD-induced cognitive impairments as assessed through novel object recognition test, the observation of dendritic spines, and the levels of BDNF or other proteins like spinophilin and ARC. Thus, modulation of JNK1 activity seems like a promising approach for the design of therapies aimed at treating metabolic-induced cognitive impairments. KEY MESSAGES: JNK1 is a link between obesity/type 2 diabetes and cognitive loss Inhibition of JNK1 is neuroprotective JNK1 constitutes a therapeutic strategy for cognitive loss. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink