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Article

Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

1
Department of Pharmacology, University of Zagreb School of Medicine, 10 000 Zagreb, Croatia
2
Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10 000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Academic Editor: Fiorella Biasi
Antioxidants 2021, 10(7), 1118; https://doi.org/10.3390/antiox10071118
Received: 6 May 2021 / Revised: 7 July 2021 / Accepted: 9 July 2021 / Published: 13 July 2021
The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model. View Full-Text
Keywords: GLP-1; streptozotocin; Alzheimer’s disease; oxidative stress; brain-gut axis; redox homeostasis GLP-1; streptozotocin; Alzheimer’s disease; oxidative stress; brain-gut axis; redox homeostasis
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MDPI and ACS Style

Homolak, J.; Babic Perhoc, A.; Knezovic, A.; Osmanovic Barilar, J.; Salkovic-Petrisic, M. Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease. Antioxidants 2021, 10, 1118. https://doi.org/10.3390/antiox10071118

AMA Style

Homolak J, Babic Perhoc A, Knezovic A, Osmanovic Barilar J, Salkovic-Petrisic M. Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease. Antioxidants. 2021; 10(7):1118. https://doi.org/10.3390/antiox10071118

Chicago/Turabian Style

Homolak, Jan, Ana Babic Perhoc, Ana Knezovic, Jelena Osmanovic Barilar, and Melita Salkovic-Petrisic. 2021. "Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease" Antioxidants 10, no. 7: 1118. https://doi.org/10.3390/antiox10071118

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