Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease.

Autor: Zago AM; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil., Carvalho FB; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil. fabiseco@yahoo.com.br., Rahmeier FL; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil., Santin M; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil., Guimarães GR; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil., Gutierres JM; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil., da C Fernandes M; Graduate Program in Pathology, Pathology Research Laboratory, Federal University of Health Sciences of Porto Alegre, Sarmento Leite, 245, Room 514, Building 3. CEP 90050-170, Porto Alegre, RS, Brazil. marneuro22@gmail.com.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 May; Vol. 61 (5), pp. 2631-2652. Date of Electronic Publication: 2023 Nov 03.
DOI: 10.1007/s12035-023-03698-w
Abstrakt: This study investigated the neuroprotective effects of exendin-4 (EXE-4), an analog of the glucagon-like peptide 1 receptor (GLP-1R) on memory and on the neuronal populations that constitute the hippocampus of rats submitted to a sporadic dementia of Alzheimer's type (SDAT). Male Wistar rats received streptozotocin (STZ icv, 3 mg/kg diluted in aCFS, 5 µl/ventricle) and were treated for 21 days with EXE-4 (10 µg/kg, ip; saline as the vehicle). Four groups were formed: vehicle, EXE-4, STZ, and STZ + EXE-4. The groups were submitted to Y-Maze (YM), object recognition (ORT), and object displacement tasks (ODT) to assess learning and memory. The brains were used for immunohistochemical and immunofluorescent techniques with antibodies to NeuN, cleaved caspase-3 (CC3), PCNA, doublecortin (DCX), synaptophysin (SYP), and insulin receptor (IR). STZ worsened spatial memory in the YMT, as well as short-term (STM) and long-term (LTM) memories in the ORT and ODT, respectively. EXE-4 protected against memory impairment in STZ animals. STZ reduced mature neuron density (NeuN) and increased cell apoptosis (CC3) in the DG, CA1, and CA3. EXE-4 protected against neuronal death in all regions. EXE-4 increased PCNA + cells in all regions of the hippocampus, and STZ attenuated this effect. STZ reduced neurogenesis in DG per se as well as synaptogenesis induced by EXE-4. EXE-4 increased immunoreactivity to IR in the CA1. From these findings, EXE-4 showed a beneficial effect on hippocampal pyramidal and granular neurons in the SDAT showing anti-apoptotic properties and promoting cell proliferation. In parallel, EXE-4 preserved the memory of SDAT rats. EXE-4 appears to enhance synapses at CA3 and DG. In conclusion, these data indicate that agonists to GLP-1R have a beneficial effect on hippocampal neurons in AD.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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