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Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

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.

SUBMITTER: Alhowail AH

PROVIDER: S-EPMC10637675 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

Alhowail Ahmad H AH Eggert Matthew M Bloemer Jenna J Pinky Priyanka D PD Woodie Lauren L Bhattacharya Subhrajit S Bhattacharya Dwipayan D Buabeid Manal A MA Smith Bruce B Dhanasekaran Muralikrishnan M Piazza Gary G Reed Miranda N MN Escobar Martha M Arnold Robert D RD Suppiramaniam Vishnu V

PloS one 20231110 11

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 ass ...[more]

PMID: 37948406

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Project description:BackgroundHippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.MethodsPilocarpine was used to induced SE in mice. SE-generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics.ResultsThe results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety-like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D-fructose-1,6-bisphosphate.ConclusionTo the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiatric and cognitive disorders.

Project description:Many survivors of stroke report attentional impairments, such as diminished concentration and distractibility. However, the effectiveness of cognitive rehabilitation for improving these impairments is uncertain.This is an update of the Cochrane Review first published in 2000 and previously updated in 2013. To determine whether people receiving cognitive rehabilitation for attention problems 1. show better outcomes in their attentional functions than those given no treatment or treatment as usual, and 2. have a better functional recovery, in terms of independence in activities of daily living, mood, and quality of life, than those given no treatment or treatment as usual. We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PsycBITE, REHABDATA and ongoing trials registers up to February 2019. We screened reference lists and tracked citations using Scopus. We included controlled clinical trials (CCTs) and randomised controlled trials (RCTs) of cognitive rehabilitation for impairments of attention for people with stroke. We did not consider listening to music, meditation, yoga, or mindfulness to be a form of cognitive rehabilitation. We only considered trials that selected people with demonstrable or self-reported attentional deficits. The primary outcomes were measures of global attentional functions, and secondary outcomes were measures of attentional domains (i.e. alertness, selective attention, sustained attention, divided attention), functional abilities, mood, and quality of life. Two review authors independently selected trials, extracted data, and assessed the risk of bias. We used the GRADE approach to assess the certainty of evidence for each outcome. We included no new trials in this update. The results are unchanged from the previous review and are based on the data of six RCTs with 223 participants. All six RCTs compared cognitive rehabilitation with a usual care control. Meta-analyses demonstrated no convincing effect of cognitive rehabilitation on subjective measures of attention either immediately after treatment (standardised mean difference (SMD) 0.53, 95% confidence interval (CI) -0.03 to 1.08; P = 0.06; 2 studies, 53 participants; very low-quality evidence) or at follow-up (SMD 0.16, 95% CI -0.23 to 0.56; P = 0.41; 2 studies, 99 participants; very low-quality evidence). People receiving cognitive rehabilitation (when compared with control) showed that measures of divided attention recorded immediately after treatment may improve (SMD 0.67, 95% CI 0.35 to 0.98; P < 0.0001; 4 studies, 165 participants; low-quality evidence), but it is uncertain that these effects persisted (SMD 0.36, 95% CI -0.04 to 0.76; P = 0.08; 2 studies, 99 participants; very low-quality evidence). There was no evidence for immediate or persistent effects of cognitive rehabilitation on alertness, selective attention, and sustained attention. There was no convincing evidence for immediate or long-term effects of cognitive rehabilitation for attentional problems on functional abilities, mood, and quality of life after stroke. The effectiveness of cognitive rehabilitation for attention deficits following stroke remains unconfirmed. The results suggest there may be an immediate effect after treatment on attentional abilities, but future studies need to assess what helps this effect persist and generalise to attentional skills in daily life. Trials also need to have higher methodological quality and better reporting.

Dataset Information

Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

Publications

Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

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