Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer’s disease DOI Creative Commons
Noor Abdulhameed,

Alice Babin,

Kim M. Hansen

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 1, 2024

Abstract Targeting brain insulin resistance (BIR) has become an attractive alternative to traditional therapeutic treatments for Alzheimer’s disease (AD). Incretin receptor agonists (IRAs), targeting either or both of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, have proven reverse BIR improve cognition in mouse models AD. We previously showed that many, but not all, IRAs can cross blood-brain barrier (BBB) after intravenous (IV) delivery. Here we determined if widespread uptake could be achieved by circumventing BBB using intranasal (IN) delivery, which added advantage minimizing adverse gastrointestinal effects systemically delivered IRAs. Of 5 radiolabeled tested (exenatide, dulaglutide, semaglutide, DA4-JC, DA5-CH) CD-1 mice, exenatide, DA4-JC were successfully distributed throughout following IN observed significant sex differences DA4-JC. Dulaglutide exhibited high hippocampus multiple neocortical areas. further found presence AD-associated Aβ pathology minimally affected dulaglutide IRAs, are best capable accessing regions most vulnerable AD (neocortex hippocampus) administration. Future studies will need performed determine IRA delivery reduce animal disorder.

Language: Английский

Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer’s disease DOI Creative Commons
Noor Abdulhameed,

Alice Babin,

Kim M. Hansen

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 1, 2024

Abstract Targeting brain insulin resistance (BIR) has become an attractive alternative to traditional therapeutic treatments for Alzheimer’s disease (AD). Incretin receptor agonists (IRAs), targeting either or both of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, have proven reverse BIR improve cognition in mouse models AD. We previously showed that many, but not all, IRAs can cross blood-brain barrier (BBB) after intravenous (IV) delivery. Here we determined if widespread uptake could be achieved by circumventing BBB using intranasal (IN) delivery, which added advantage minimizing adverse gastrointestinal effects systemically delivered IRAs. Of 5 radiolabeled tested (exenatide, dulaglutide, semaglutide, DA4-JC, DA5-CH) CD-1 mice, exenatide, DA4-JC were successfully distributed throughout following IN observed significant sex differences DA4-JC. Dulaglutide exhibited high hippocampus multiple neocortical areas. further found presence AD-associated Aβ pathology minimally affected dulaglutide IRAs, are best capable accessing regions most vulnerable AD (neocortex hippocampus) administration. Future studies will need performed determine IRA delivery reduce animal disorder.

Language: Английский

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