c-Jun N-terminal Kinase 1 ablation protects against metabolic-induced hippocampal cognitive impairments.
Oriol BusquetsMiren EttchetoÀuria EritjaTriana Espinosa-JiménezEster VerdaguerJordi OlloquequiCarlos Beas-ZarateRuben Dario Castro-TorresGemma CasadesúsCarme AuladellMònica BullóJaume FolchAntonio Camins EspunyPublished in: Journal of molecular medicine (Berlin, Germany) (2019)
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.
Keyphrases
- high fat diet
- insulin resistance
- signaling pathway
- cell death
- type diabetes
- induced apoptosis
- adipose tissue
- high fat diet induced
- high glucose
- oxidative stress
- body weight
- diabetic rats
- metabolic syndrome
- drug induced
- skeletal muscle
- cerebral ischemia
- endothelial cells
- inflammatory response
- polycystic ovary syndrome
- white matter
- working memory
- big data
- multiple sclerosis
- brain injury
- radiofrequency ablation
- subarachnoid hemorrhage
- blood brain barrier
- human health
- atrial fibrillation