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- Title
Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.
- Authors
Alhowail, Ahmad H.; Eggert, Matthew; Bloemer, Jenna; Pinky, Priyanka D.; Woodie, Lauren; Bhattacharya, Subhrajit; Bhattacharya, Dwipayan; Buabeid, Manal A.; Smith, Bruce; Dhanasekaran, Muralikrishnan; Piazza, Gary; Reed, Miranda N.; Escobar, Martha; Arnold, Robert D.; Suppiramaniam, Vishnu
- Abstract
Chemotherapy-induced memory loss ("chemobrain") can occur following treatment with the widely used chemotherapeutic agent doxorubicin (DOX). However, the mechanisms through which DOX induces cognitive dysfunction are not clear, and there are no commercially available therapies for its treatment or prevention. Therefore, the aim of this study was to determine the therapeutic potential of phenyl-2-aminoethyl selenide (PAESe), an antioxidant drug previously demonstrated to reduce cardiotoxicity associated with DOX treatment, against DOX-induced chemobrain. Four groups of male athymic NCr nude (nu/nu) mice received five weekly tail-vein injections of saline (Control group), 5 mg/kg of DOX (DOX group), 10 mg/kg PAESe (PAESe group), or 5 mg/kg DOX and 10 mg/kg PAESe (DOX+PAESe group). Spatial memory was evaluated using Y-maze and novel object location tasks, while synaptic plasticity was assessed through the measurement of field excitatory postsynaptic potentials from the Schaffer collateral circuit. Western blot analyses were performed to assess hippocampal protein and phosphorylation levels. In this model, DOX impaired synaptic plasticity and memory, and increased phosphorylation of protein kinase B (Akt) and extracellular-regulated kinase (ERK). Co-administration of PAESe reduced Akt and ERK phosphorylation and ameliorated the synaptic and memory deficits associated with DOX treatment.
- Subjects
DOXORUBICIN; LONG-term potentiation; EXCITATORY postsynaptic potential; PROTEIN kinase B; WESTERN immunoblotting; HIPPOCAMPUS (Brain)
- Publication
PLoS ONE, 2023, Vol 18, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0294280