Naslov
The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease

Autori
Osmanović Barilar, Jelena ; Babić Perhoč, Ana ; Knezović, Ana ; Homolak, Jan ; Virag, Davor ; Šalković-Petrišić, Melita

Izvornik
Biomedicines (2227-9059) 11 (2023), 4; 1025, 17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
sodium–glucose cotransporter inhibitor ; streptozotocin ; Alzheimer’s disease ; glucagon-like peptide 1

Sažetak
First_pagesettingsOrder Article Reprints Open AccessArticle The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease by Jelena Osmanović Barilar *ORCID, Ana Babić PerhočORCID, Ana KnezovićORCID, Jan HomolakORCID, Davor ViragORCID andMelita Šalković- Petrišić Department of Pharmacology and Croatian, Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia * Author to whom correspondence should be addressed. Biomedicines 2023, 11(4), 1025 ; https://doi.org/10.3390/biomedicines11041025 Received: 26 January 2023 / Revised: 16 March 2023 / Accepted: 23 March 2023 / Published: 27 March 2023 (This article belongs to the Special Issue Molecular Research of Neurodegenerative and Psychiatric Diseases) Download Browse Figures Review Reports Versions Notes Abstract Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive parameters in a rat model of sAD. Adult male Wistar rats were randomized to a control (CTR), an sAD-model group induced by intracerebroventricular streptozotocin (STZ-icv ; 3 mg/kg), a CTR+SGLTI, or an STZ-icv+SGLTI group. Two-month-long oral (gavage) SGLTI treatment (10 mg/kg) was initiated 1 month after STZ-icv and cognitive performance tested prior to sacrifice. SGLTI treatment significantly decreased plasma glucose levels only in the CTR group and failed to correct STZ-icv- induced cognitive deficit. In both the CTR and STZ-icv groups, SGLTI treatment diminished weight gain, decreased amyloid beta (Aβ) 1-42 in duodenum, and decreased the plasma levels of total glucagon-like peptide 1 (GLP-1), while the levels of active GLP-1, as well as both total and active glucose-dependent insulinotropic polypeptide, remained unchanged, compared to their respective controls. The increment in GLP-1 levels in the cerebrospinal fluid and its effect on Aβ 1- 42 in duodenum could be one of the molecular mechanisms by which SGLTIs indirectly induce pleiotropic beneficial effects.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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