Hyperglycemia-Driven Insulin Signaling Defects Promote Parkinson's Disease-like Pathology in Mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00081406" target="_blank" >RIV/00159816:_____/24:00081406 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00138590

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acsptsci.4c00586" target="_blank" >https://pubs.acs.org/doi/10.1021/acsptsci.4c00586</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsptsci.4c00586" target="_blank" >10.1021/acsptsci.4c00586</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hyperglycemia-Driven Insulin Signaling Defects Promote Parkinson's Disease-like Pathology in Mice

Popis výsledku v původním jazyce

This study aims to determine the effect of chronic hyperglycemia, induced by a high-fat diet and STZ-induced diabetes, on the development of Parkinson&apos;s disease-like characteristics. Understanding this relationship is crucial in pharmacology, neurology, and diabetes, as it could potentially lead to developing new therapeutic strategies for Parkinson&apos;s disease. Our study employed a comprehensive approach to investigate the effect of hyperglycemia on Parkinson&apos;s disease-like characteristics. Hyperglycemia was induced by a high-fat diet for 6- and 9-week duration with a single intraperitoneal STZ (100 mg/kg) injection at week 5 in C57/BL6 mice. Rotenone (10 mg/kg p.o.) was administered to C57/BL6 mice for 6 and 9 weeks. Time-dependent behavioral studies (wire-hang tests, pole tests, Y-maze tests, and round beam walk tests) were carried out to monitor pathology progression and deficits. Molecular protein levels (GLP1, PI3K, AKT, GSK-3 beta, NF-kappa B, and alpha-syn), oxidative stress (GSH and MDA) parameters, and histopathological alterations (H&amp;E and Nissl staining) were determined after 6 weeks as well as 9 weeks. After 9 weeks of study, molecular protein expression (p-AKT and p-alpha-syn) was determined. Hyperglycemia induced by HFD and STZ induced significant motor impairment in mice, correlated with the rotenone group. Insulin receptor signaling (GLP1/PI3K/AKT) was found to be disrupted in the HFD+STZ group and also in rotenone-treated mice, which further enhanced phosphorylation of alpha-syn, suggesting its role in alpha-syn accumulation. Histopathological alterations indicating neuroinflammation and neurodegeneration were quite evident in the HFD+STZ and rotenone groups. Exposure to hyperglycemia induced by HFD+STZ administration exhibits PD-like characteristics after 9 weeks of duration, which was correlative with rotenone-induced PD-like symptoms.

Název v anglickém jazyce

Hyperglycemia-Driven Insulin Signaling Defects Promote Parkinson's Disease-like Pathology in Mice

Popis výsledku anglicky

This study aims to determine the effect of chronic hyperglycemia, induced by a high-fat diet and STZ-induced diabetes, on the development of Parkinson&apos;s disease-like characteristics. Understanding this relationship is crucial in pharmacology, neurology, and diabetes, as it could potentially lead to developing new therapeutic strategies for Parkinson&apos;s disease. Our study employed a comprehensive approach to investigate the effect of hyperglycemia on Parkinson&apos;s disease-like characteristics. Hyperglycemia was induced by a high-fat diet for 6- and 9-week duration with a single intraperitoneal STZ (100 mg/kg) injection at week 5 in C57/BL6 mice. Rotenone (10 mg/kg p.o.) was administered to C57/BL6 mice for 6 and 9 weeks. Time-dependent behavioral studies (wire-hang tests, pole tests, Y-maze tests, and round beam walk tests) were carried out to monitor pathology progression and deficits. Molecular protein levels (GLP1, PI3K, AKT, GSK-3 beta, NF-kappa B, and alpha-syn), oxidative stress (GSH and MDA) parameters, and histopathological alterations (H&amp;E and Nissl staining) were determined after 6 weeks as well as 9 weeks. After 9 weeks of study, molecular protein expression (p-AKT and p-alpha-syn) was determined. Hyperglycemia induced by HFD and STZ induced significant motor impairment in mice, correlated with the rotenone group. Insulin receptor signaling (GLP1/PI3K/AKT) was found to be disrupted in the HFD+STZ group and also in rotenone-treated mice, which further enhanced phosphorylation of alpha-syn, suggesting its role in alpha-syn accumulation. Histopathological alterations indicating neuroinflammation and neurodegeneration were quite evident in the HFD+STZ and rotenone groups. Exposure to hyperglycemia induced by HFD+STZ administration exhibits PD-like characteristics after 9 weeks of duration, which was correlative with rotenone-induced PD-like symptoms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/LX22NPO5107" target="_blank" >LX22NPO5107: Národní ústav pro neurologický výzkum</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Pharmacology &amp; Translational Science

ISSN

2575-9108

e-ISSN

2575-9108

Svazek periodika

7

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

4155-4164

Kód UT WoS článku

001366369100001

EID výsledku v databázi Scopus

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