c-Jun N-terminal Kinase 1 ablation protects against metabolic-induced hippocampal cognitive impairments

Oriol Busquets, Miren Ettcheto, Àuria Eritja, Triana Espinosa-Jiménez, Ester Verdaguer, Jordi Olloquequi, Carlos Beas-Zarate, Ruben Dario Castro-Torres, & Gemma Casadesús, Carme Auladell, Mònica Bulló, Jaume Folch, Antoni Camins1*

Departament de Farmacologia, Toxicologia i Química Terapèutica

Abstract:  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 Nterminal Kinase 1 (JNK1) is a potential key modulator of these mechanisms. The current study identifies a protective effect of whole-bodyJNK1knockoutinthepresenceofahigh-fatdiet(HFD).Specifically,thedatasuggestthatmicemissingJNK1show 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.

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