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  Guanosine prevents anhedonic-like behavior and impairment in hippocampal glutamate transport following amyloid-β1–40 administration in mice.

Lanznaster, D., Mack, J. M., Coelho, V., Ganzella, M., Almeida, R. F., Dal-Cim, T., et al. (2017). Guanosine prevents anhedonic-like behavior and impairment in hippocampal glutamate transport following amyloid-β1–40 administration in mice. Molecular Neurobiology, 54(7), 5482-5496. doi:10.1007/s12035-016-0082-1.

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Lanznaster, D., Autor
Mack, J. M., Autor
Coelho, V., Autor
Ganzella, M.1, Autor           
Almeida, R. F., Autor
Dal-Cim, T., Autor
Hansel, G., Autor
Zimmer, E. R., Autor
Souza, D. O., Autor
Prediger, R. D., Autor
Tasca, C. I., Autor
Affiliations:
1Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_578595              

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Schlagwörter: Alzheimer's disease; Guanosine; A beta(1-40); Learning and memory; Anhedonia; Glutamate transport
 Zusammenfassung: Amyloid-beta (A beta) peptides are the major neuropathological hallmarks related with Alzheimer's disease (AD). A beta peptides trigger several biochemical mechanisms of neurotoxicity, including neuroinflammation and glutamatergic neurotransmission impairment. Guanosine is the endogenous guanine-derived nucleoside that modulates the glutamatergic system and the cellular redox status, thus acting as a neuroprotective agent. Here, we investigated the putative neuroprotective effect of guanosine in an AD-like mouse model. Adult mice received a single intracerebroventricular injection of A beta(1-40) (400 pmol/site) or vehicle and then were treated immediately, 3 h later, and once a day during the subsequent 14 days with guanosine (8 mg/kg, intraperitoneally). A beta(1-40) or guanosine did not alter mouse locomotor activity and anxiety-related behaviors. A beta(1-40)-treated mice displayed short-term memory deficit in the object location task that was prevented by guanosine. Guanosine prevented the A beta(1-40)-induced increase in latency to grooming in the splash test, an indicative of anhedonia. A beta(1-40) increased Na+-independent glutamate uptake in ex vivo hippocampal slices, and guanosine reversed it to control levels. The repeated administration of guanosine increased hippocampal GDP levels, which was not observed in the group treated with A beta plus guanosine. A beta(1-40) induced an increase in hippocampal ADP levels. A beta(1-40) decreased GFAP expression in the hippocampal CA1 region, an effect not modified by guanosine. No differences were observed concerning synaptophysin and NeuN immunolabeling. Together, these results show that guanosine prevents memory deficit and anhedonic-like behavior induced by A beta(1-40) that seem to be linked to glutamate transport unbalance and alterations on purine and metabolite levels in mouse hippocampus.

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Sprache(n): eng - English
 Datum: 2016-09-062017-09
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1007/s12035-016-0082-1
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Titel: Molecular Neurobiology
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 54 (7) Artikelnummer: - Start- / Endseite: 5482 - 5496 Identifikator: -