RESUMO
Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.
Assuntos
Animais Recém-Nascidos , Cognição , Hipocampo , Sevoflurano , Sevoflurano/farmacologia , Animais , Feminino , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ratos , Cognição/efeitos dos fármacos , Fatores de Tempo , Aprendizagem em Labirinto/efeitos dos fármacos , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/efeitos adversos , Apoptose/efeitos dos fármacos , Fatores Sexuais , Ratos Sprague-Dawley , Éteres Metílicos/farmacologia , Western Blotting , Gasometria , Disfunção Cognitiva/induzido quimicamenteRESUMO
Evidence has shown that consuming trans fatty acids (TFA) during development leads to their incorporation into the nervous tissue, resulting in neurological changes in flies. In this study, Drosophila melanogaster was exposed to different concentrations of hydrogenated vegetable fat (HVF) during development: substitute hydrogenated vegetable fat (SHVF), HVF 10 %, and HVF 20 %. The objective was to evaluate the effects of early trans fat exposure on cognition and associated pathways in flies. The results showed that early TFA exposure provoked a cerebral redox imbalance, as confirmed by increased reactive species (HVF 10 and 20 %) and lipid peroxidation (SHVF, HVF 10, and 20 %), reduced nuclear factor erythroid 2-related factor 2 immunoreactivity (HVF 10 and 20 %), and increased heat shock protein 70 (HVF 20 %), which was possibly responsible for decreasing superoxide dismutase (SHVF, HVF 10, and 20 %) and catalase (HVF 20 %) activities. Furthermore, the presence of TFA in nervous tissue impaired learning (HVF 10 and 20 %) and memory at 6 and 24 h (SHVF, HVF 10, and 20 %). These cognitive impairments may be linked to reduced Shank levels (HVF 20 %) and increased acetylcholinesterase activity (SHVF, HVF 10 and 20 %) observed. Our findings demonstrate that early exposure to trans fat leads to cerebral redox imbalance, altering proteins associated with stress, synaptic plasticity, and the cholinergic system, consequently leading to cognitive impairment in flies.
Assuntos
Disfunção Cognitiva , Ácidos Graxos trans , Animais , Drosophila melanogaster , Ácidos Graxos trans/toxicidade , Acetilcolinesterase , Estresse Oxidativo , Disfunção Cognitiva/induzido quimicamente , Plasticidade NeuronalRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Lignanas , Fármacos Neuroprotetores , Camundongos , Masculino , Animais , Peptídeos beta-Amiloides/metabolismo , Memantina/farmacologia , Antioxidantes/farmacologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Lignanas/farmacologia , Furanos/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Neuroprotetores/farmacologia , Hipocampo/metabolismoRESUMO
PURPOSE: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. METHODS: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. RESULTS: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid ß; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1ß), and tumor necrosis factor-α. Sevoflurane significantly reduced the activity of caspase-3. CONCLUSIONS: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.
Assuntos
Anestésicos Inalatórios , Disfunção Cognitiva , Isoflurano , Fármacos Neuroprotetores , Ratos , Animais , Isoflurano/efeitos adversos , Sevoflurano/uso terapêutico , Antioxidantes/uso terapêutico , Interleucina-10 , Anestésicos Inalatórios/efeitos adversos , Neuroproteção , Acetilcolina/efeitos adversos , Peptídeos beta-Amiloides/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Fármacos Neuroprotetores/farmacologiaRESUMO
Chemotherapy is one of the most widely used treatments for breast cancer (BC). However, there is evidence of side effects like cognitive changes related to the chemotherapy treatment. The aim of the study was not only to summarize the existing evidence on the relationship between chemotherapy and cognitive performance in women with BC but also to identify additional consequences and aspects associated with these impairments. We conducted a systematic review with meta-analysis and meta-regression to present updated information on the matter. We retrieved data from the databases PubMed, Web of Science, PsycINFO, CINAHL, and Scopus. Twenty studies comprising over 2,500 women were examined and the results indicated that chemotherapy can compromise cognition in women with BC (-1.10 OR [95%CI: -1.81 to -0.74], P<0.01), with working memory (-0.49 OR [95%CI: -0.85 to -0.13], P=0.03) being the most affected among the domains. Furthermore, additional data indicated that cognitive impairment is most likely amid women with BC having a lower education level (Q=4.85, P=0.02). Our results suggested that chemotherapy affects cognitive functions in women with BC, and certain characteristics can worsen the deterioration. A comprehensive study of women with breast cancer and existing predictors contributes to optimized personal journeys, elevated life prospects, and advanced care that can also aid prognosis and therapeutic approaches.
Assuntos
Neoplasias da Mama , Disfunção Cognitiva , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , CogniçãoRESUMO
Background: Patients with breast cancer may experience cognitive difficulties from chemotherapy. This alteration is called Chemoinduced Cognitive Impairment, also known as Chemobrain or Chemofog. Objective: To identify the cognitive profile and the characteristics of the neuropsychological assessment in this population. Method: PubMed, SpringerLink and SciELO databases were revised. Articles from 1994 to September 2021 were selected. Keywords related to the study topic were used. Results: Chemotherapy can cause cognitive impairment between 15 and 50% of women. This disturbance may be from multiple aetiologies and can be associated with biological factors and functional and/or structural changes of the CNS. Sociodemographic, clinical and psychological factors should be considered as modulating variables. It manifests mainly with memory problems, executive function, attention and processing speed impairment. It can be measured through neuropsychological evaluation instruments. Discussion and conclusion: We suggest that chemo-induced cognitive impairment should be included to the informed consent. Further development of longitudinal studies complemented with neuroimages that allow us to advance in the knowledge of this problem is recommended. A neuropsychological protocol is proposed, which includes screening tests, clinical scales, specific cognitive tests and quality of life questionnaires, within the recommendations of the International Cognition and Cancer Task Force.
ANTECEDENTES: Los pacientes con cáncer de mama pueden experimentar dificultades cognitivas por recibir quimioterapia. Dicha alteración es denominada Deterioro Cognitivo Quimioinducido, también es conocida como Chemobrain o Chemofog. OBJETIVO: Identificar el perfil cognitivo y las características de la evaluación neuropsicológica de esta población. Método: Se consultaron las bases de datos PubMed, SpringerLink y SciELO. Se seleccionaron artículos de 1994 hasta septiembre de 2021. Fueron utilizadas palabras claves relacionadas con el tema de estudio. RESULTADOS: La quimioterapia puede producir un deterioro cognitivo entre el 15 y el 50% de las mujeres. Dicha alteración es de etiología múltiple y puede asociarse a factores biológicos y a cambios funcionales y/o estructurales del SNC. Se deben de considerar los factores sociodemográficos, clínicos y psicológicos como variables moduladoras. Se manifiesta principalmente en problemas de memoria, función ejecutiva, atención y velocidad de procesamiento. Esta alteración puede ser mensurada a través de los instrumentos de evaluación neuropsicológica disponibles. Discusión y conclusión: Se sugiere que la afectación cognitiva quimioinducida sea incorporada en el consentimiento informado. Se recomienda un mayor desarrollo de estudios longitudinales que se complementen con técnicas de neuroimágenes que permitan avanzar en el conocimiento de esta problemática. Se propone un protocolo de evaluación neuropsicológica, que incluye pruebas de screening, escalas clínicas, test neuropsicológicos específicos y de calidad de vida, según las recomendaciones del International Cognition and Cancer Task Force.
Assuntos
Neoplasias da Mama , Transtornos Cognitivos , Disfunção Cognitiva , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida/psicologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/complicações , Transtornos Cognitivos/psicologia , CogniçãoRESUMO
OBJECTIVES: Potentially inappropriate medications (PIM), especially those with potential effects on the central nervous system, can increase the risk of cognitive impairment. We investigated the association of the use of PIM and PIM that may impair cognition (PIM-Cog) with cognitive performance among older adults. METHODS: In this cross-sectional study with 2,626 participants, PIM and PIM-Cog were defined by the 2019 American Geriatrics Society Beers criteria. We calculated global cognition and memory, verbal fluency, and Trail Making Test B version (TMT-B) z-scores. Linear regression models adjusted for sociodemographic and clinical variables were used to investigate the association between PIM and cognition. RESULTS: 27% and 7% of the sample (mean age = 65.1 ± 4.1 years old, 54% women, and 61% White) used at least one PIM and PIM-cog, respectively. PIM was associated with poor performance in the TMT-B (ß = -0.17, 95% Cl = -0.29; -0.05, p = 0.007). PIM-Cog was also associated with poor TMT-B performance (ß = -0.08, 95% Cl = -0.15; -0.01, p = 0.025). CONCLUSION: The use of PIM and PIM-Cog was associated with poor executive function among older adults. The review of PIM use and the deprescription of these drugs may be an effective way to improve cognitive function.
Assuntos
Disfunção Cognitiva , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Feminino , Estados Unidos , Idoso , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Prescrição Inadequada , Cognição , Disfunção Cognitiva/induzido quimicamenteRESUMO
OBJECTIVES: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. METHOD: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. RESULTS: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under iso-treatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1ß, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1-positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. CONCLUSIONS: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.
Assuntos
Anestesia , Disfunção Cognitiva , Isoflurano , Animais , Camundongos , Animais Recém-Nascidos , Apoptose , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Isoflurano/efeitos adversos , Isoflurano/metabolismoRESUMO
Among the potential adverse effects of breast cancer treatment, chemotherapy-related cognitive impairment (CRCI) has gained increased attention in the past years. In this review, we provide an overview of the literature regarding CRCI in breast cancer, focusing on three main aspects. The first aspect relates to the molecular mechanisms linking individual drugs commonly used to treat breast cancer and CRCI, which include oxidative stress and inflammation, reduced neurogenesis, reduced levels of specific neurotransmitters, alterations in neuronal dendrites and spines, and impairment in myelin production. The second aspect is related to the clinical characteristics of CRCI in patients with breast cancer treated with different drug combinations. Data suggest the incidence rates of CRCI in breast cancer vary considerably, and may affect more than 50% of treated patients. Both chemotherapy regimens with or without anthracyclines have been associated with CRCI manifestations. While cross-sectional studies suggest the presence of symptoms up to 20 years after treatment, longitudinal studies confirm cognitive impairments lasting for at most 4 years after the end of chemotherapy. The third and final aspect is related to possible therapeutic interventions. Although there is still no standard of care to treat CRCI, several pharmacological and non-pharmacological approaches have shown interesting results. In summary, even if cognitive impairments derived from chemotherapy resolve with time, awareness of CRCI is crucial to provide patients with a better understanding of the syndrome and to offer them the best care directed at improving quality of life.
Assuntos
Neoplasias da Mama , Comprometimento Cognitivo Relacionado à Quimioterapia , Disfunção Cognitiva , Neoplasias da Mama/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Qualidade de Vida/psicologiaRESUMO
The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.