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Upregulation of neurotrophins by S 47445, a novel positive allosteric modulator of AMPA receptors in aged rats.

Authors :
Calabrese, Francesca
Savino, Elisa
Mocaer, Elisabeth
Bretin, Sylvie
Racagni, Giorgio
Riva, Marco A.
Source :
Pharmacological Research. Jul2017, Vol. 121, p59-69. 11p.
Publication Year :
2017

Abstract

At molecular levels, it has been shown that aging is associated with alterations in neuroplastic mechanisms. In this study, it was examined if the altered expression of neurotrophins observed in aged rats could be corrected by a chronic treatment with S 47445 (1–3–10 mg/kg, p.o.), a novel selective positive allosteric modulator of the AMPA receptors. Both the mRNA and the protein levels of the neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal cortex and hippocampus (ventral and dorsal) of aged rats. It was found that 2-week-treatment with S 47445 corrected the age-related deficits of these neurotrophins and/or positively modulated their expression in comparison to vehicle aged rats in the range of procognitive and antidepressant active doses in rodents. Collectively, the ability of S 47445 to modulate various neurotrophins demonstrated its neurotrophic properties in two major brain structures involved in cognition and mood regulation suggesting its therapeutic potential for improving several diseases such as Alzheimer’s disease and/or Major Depressive Disorders. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10436618
Volume :
121
Database :
Academic Search Index
Journal :
Pharmacological Research
Publication Type :
Academic Journal
Accession number :
123505929
Full Text :
https://doi.org/10.1016/j.phrs.2017.04.019