Autor(en): | Iloun, Parisa Abbasnejad, Zahra Janahmadi, Mahyar Ahmadiani, Abolhassan Ghasemi, Rasoul |
Titel: | Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment |
Sonstige Titel: | effects of insulin treatment |
Sprache (ISO): | en |
Zusammenfassung: | Despite the consensus that neuro-inflammation and insulin resistance (IR) are two hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the development of IR remain uncharacterized. MAPKs are signaling molecules that are implicated in the pathology of AD and have a role in IR development. Given that inflammatory mediators are shown to interfere with insulin signaling pathway in different cell types, the present work aimed to investigate whether neuro-inflammation induced memory loss is associated with hippocampal IR and whether insulin treatment protects against this IR. Subsequently, possible roles of MAPKs in this situation were investigated. Male Wistar rats were cannulated, and LPS (15 μg, day 0), insulin (3 mU) or saline (vehicle) were administered intra-cerebroventricularly (ICV) (days 1-6). Spatial memory performance was assessed during days 7-10 by Morris Water Maze test. Consequently, analysis of the amount of hippocampal phosphorylated forms of P38, JNK, ERK, IRS1 (ser307) and Akt (ser473) were done by Western blot. The outcomes indicated that while LPS induced memory loss and hippocampal IR (shown by elevated IRS1 and decreased Akt phosphorylation),insulin treatment nullified these effects. Molecular results also showed that LPS mediated IR and memory loss are associated with P38 but not JNK and ERK activation; this P38 activation was reversed by insulin treatment. These observations implied that one of the ways by which neuro-inflammation participates in AD is via induction of IR. It seems that this IR is mainly mediated by P38. Therefore, P38 could be considered as a molecular target for preventing IR development. |
Schlagwörter: | Insulin Alzheimer disease insulin receptor substrate-1 insulin resistance neuro-inflammation MAPK |
URI: | http://hdl.handle.net/2003/37844 http://dx.doi.org/10.17877/DE290R-19839 |
Erscheinungsdatum: | 2018-08-20 |
Enthalten in den Sammlungen: | Original Articles |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
---|---|---|---|---|
Ghasemi_20082018_proof.pdf | DNB | 530.92 kB | Adobe PDF | Öffnen/Anzeigen |
Ghasemi_20082018_supplementary_material.zip | DNB | 1.37 MB | zip | Öffnen/Anzeigen |
Diese Ressource ist urheberrechtlich geschützt. |
Diese Ressource ist urheberrechtlich geschützt.
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