Paulina Sepúlveda
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Paulina Sepúlveda has a total of 54 co-authors. Here are the top co-authors by number of shared publications:
- Cristian Sandoval
Carrera de Terapia Ocupacional, Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Temuco 4810101, Chile
3 shared publications Edgar Vásquez-Carrasco
School of Occupational Therapy, Faculty of Psychology, Universidad de Talca
3 shared publicationsJordan Hernandez-Martinez
Department of Physical Activity Sciences, Universidad de Los Lagos
3 shared publications- Alexis Sepúlveda-Lara
Doctorado en Ciencias mención Biología Celular y Molecular Aplicada, Facultad de Ciencias Agropecuarias, Universidad de La Frontera, Temuco 4811230, Chile
2 shared publications Cristian Sandoval-Vásquez
Departamento de Medicina Interna, Facultad de Medicina, Universidad de La Frontera
2 shared publications- Edgar Vásquez-Carrasco
School of Occupational Therapy, Faculty of Psychology, Universidad de Talca, Talca 3465548, Chile
2 shared publications
Latest Publications
- Open Access
- 17 September 2026
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 17, 1969890
Preclinical efficacy and safety of drug-loaded porous silicon nanoparticles for cancer treatment: a systematic review of in vitro and in vivo studies
Introduction: Porous silicon nanoparticles (pSiNPs) are promising carriers for anticancer therapy because of their high drug-loading capacity, modifiable surface properties, and potential for stimulus-responsive drug release. This systematic review assessed the efficacy and safety of drug-loaded pSiNPs in in vitro and in vivo cancer models. Methods: Searches were conducted from database inception to 30 July 2026. Eligible studies were controlled original investigations evaluating pSiNPs loaded with at least one anticancer drug and reporting quantitative antitumor outcomes. Study selection followed PRISMA 2020 guidelines, and the protocol was registered in PROSPERO (CRD420251076592). Given the substantial methodological heterogeneity, findings were synthesized narratively. In vitro study reliability was appraised using an explicitly adapted ToxRTool framework, whereas animal-study risk of bias was assessed with the SYRCLE tool. Results: The search strategy identified 974 records, of which 22 met the inclusion; eight included animal experiments. Targeting ligands, polymeric coatings, and pH-, redox-, magnetic-, or near-infrared-responsive systems generally improved cellular uptake, drug release, cytotoxicity, and antitumor activity relative to study-specific comparators. Most in vitro studies were classified as reliable with restrictions, while several animal-study domains had unclear risk of bias because key safeguards were insufficiently reported. Conclusion: Drug-loaded pSiNPs show promising preclinical anticancer activity, but the evidence is dominated by in vitro proof-of-concept studies. Animal evidence remains limited and does not establish long-term systemic safety or biocompatibility. Standardized nanoparticle characterization, rigorous animal designs, and comprehensive long-term safety and biodistribution studies are required before clinical translation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076592 .
- 17 September 2026
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 17, 1969890
Open AccessPreclinical efficacy and safety of drug-loaded porous silicon nanoparticles for cancer treatment: a systematic review of in vitro and in vivo studies
Introduction: Porous silicon nanoparticles (pSiNPs) are promising carriers for anticancer therapy because of their high drug-loading capacity, modifiable surface properties, and potential for stimulus-responsive drug release. This systematic review assessed the efficacy and safety of drug-loaded pSiNPs in in vitro and in vivo cancer models. Methods: Searches were conducted from database inception to 30 July 2026. Eligible studies were controlled original investigations evaluating pSiNPs loaded with at least one anticancer drug and reporting quantitative antitumor outcomes. Study selection followed PRISMA 2020 guidelines, and the protocol was registered in PROSPERO (CRD420251076592). Given the substantial methodological heterogeneity, findings were synthesized narratively. In vitro study reliability was appraised using an explicitly adapted ToxRTool framework, whereas animal-study risk of bias was assessed with the SYRCLE tool. Results: The search strategy identified 974 records, of which 22 met the inclusion; eight included animal experiments. Targeting ligands, polymeric coatings, and pH-, redox-, magnetic-, or near-infrared-responsive systems generally improved cellular uptake, drug release, cytotoxicity, and antitumor activity relative to study-specific comparators. Most in vitro studies were classified as reliable with restrictions, while several animal-study domains had unclear risk of bias because key safeguards were insufficiently reported. Conclusion: Drug-loaded pSiNPs show promising preclinical anticancer activity, but the evidence is dominated by in vitro proof-of-concept studies. Animal evidence remains limited and does not establish long-term systemic safety or biocompatibility. Standardized nanoparticle characterization, rigorous animal designs, and comprehensive long-term safety and biodistribution studies are required before clinical translation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076592 .
- Open Access
- 23 April 2026
- Published by Frontiers Media SA in Frontiers in Public Health
- Vol. 14, 1806558
Study protocol for a randomized controlled trial of a culturally adapted cardiovascular dance intervention in Mapuche women with obesity
Background: In rural Indigenous women, physical inactivity is a major modifiable risk factor for cardiometabolic illness and obesity. Thus, the objective was to describe the methodological design required to develop a randomized controlled trial to compare a culturally adapted cardiovascular dance intervention to traditional exercise on physical health, quality of life, and exercise-related psychosocial outcomes in rural Indigenous women with overweight/obesity as key determinants cardiometabolic conditions. Methods: Randomized, double-blind, parallel-group clinical trial. Twenty-two adults Mapuche women with overweight or obesity and cardiometabolic disorders from an Indigenous Community in Padre Las Casas, Chile, will be randomly allocated to a control group ( n = 11) or a culturally adapted cardiovascular dance intervention group ( n = 11). Two groups will receive one-hour supervision three times a week for 12 weeks. The primary goal is cardiorespiratory fitness, whereas secondary outcomes include physical health indices, health-related quality of life, motivation for physical activity, and perceived exercise barriers and advantages. Results: The culturally customized intervention is anticipated to yield increased levels of emotional well-being, perceived self-efficacy, and adherence in comparison to conventional exercise. The incorporation of Mapuche cultural elements, particularly traditional dancing, has the potential to enhance physical health, foster social engagement, reinforce cultural identity, and enhance community engagement. Conclusion: The objective of this trial is to evaluate the potential benefits and viability of culturally tailored physical activity interventions for Indigenous women. This will enhance the effectiveness of health promotion strategies that are context-specific and inclusive, as well as resolve a significant gap in the scientific literature. Clinical trials registration: Clinicaltrials.gov/study/NCT06903455 , identifier NCT06903455
- 23 April 2026
- Published by Frontiers Media SA in Frontiers in Public Health
- Vol. 14, 1806558
Open AccessStudy protocol for a randomized controlled trial of a culturally adapted cardiovascular dance intervention in Mapuche women with obesity
Background: In rural Indigenous women, physical inactivity is a major modifiable risk factor for cardiometabolic illness and obesity. Thus, the objective was to describe the methodological design required to develop a randomized controlled trial to compare a culturally adapted cardiovascular dance intervention to traditional exercise on physical health, quality of life, and exercise-related psychosocial outcomes in rural Indigenous women with overweight/obesity as key determinants cardiometabolic conditions. Methods: Randomized, double-blind, parallel-group clinical trial. Twenty-two adults Mapuche women with overweight or obesity and cardiometabolic disorders from an Indigenous Community in Padre Las Casas, Chile, will be randomly allocated to a control group ( n = 11) or a culturally adapted cardiovascular dance intervention group ( n = 11). Two groups will receive one-hour supervision three times a week for 12 weeks. The primary goal is cardiorespiratory fitness, whereas secondary outcomes include physical health indices, health-related quality of life, motivation for physical activity, and perceived exercise barriers and advantages. Results: The culturally customized intervention is anticipated to yield increased levels of emotional well-being, perceived self-efficacy, and adherence in comparison to conventional exercise. The incorporation of Mapuche cultural elements, particularly traditional dancing, has the potential to enhance physical health, foster social engagement, reinforce cultural identity, and enhance community engagement. Conclusion: The objective of this trial is to evaluate the potential benefits and viability of culturally tailored physical activity interventions for Indigenous women. This will enhance the effectiveness of health promotion strategies that are context-specific and inclusive, as well as resolve a significant gap in the scientific literature. Clinical trials registration: Clinicaltrials.gov/study/NCT06903455 , identifier NCT06903455
- Open Access
- 5 January 2026
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 16, 1710176
Effectiveness of drug-loaded poly(ethylene glycol) and poly(lactic-co-glycolic-acid) nanoparticles in the in vitro treatment of breast cancer: a systematic review
Background: Breast cancer treatment remains a major challenge to modern medicine and has driven the need for nanotechnology-based strategies to improve drug delivery and overcome chemoresistance. Poly(ethylene glycol) and poly (lactic-co-glycolic acid) (PEG–PLGA) nanoparticles (NPs) are a type of FDA-approved biodegradable copolymer (lactic + glycolic acids) that degrades into non-toxic metabolites (lactic acid and glycolic acid); it has emerged as a promising drug carrier owing to its biocompatibility, sustained release properties, and ability to enhance the cellular uptake of chemotherapeutic agents. This systematic review examines the efficacies of PEG–PLGA nanoparticles loaded with antineoplastic drugs on in vitro models of breast cancer cell lines. Methods: Following PRISMA guidelines, we conducted a comprehensive search of the Web of Science, Embase, MEDLINE, and Scopus databases to identify experimental studies published between 2014 and August 2025 that evaluated PEG–PLGA formulations applied to breast cancer cell lines. The methodological quality of each study was appraised using the National Institute for Health and Care Excellence (NICE) criteria. Results: Thirteen studies were chosen based on our inclusion criteria. Here, the PEG–PLGA nanoparticles were predominantly spherical (30–210 nm) and exhibited controlled release kinetics. Compared with free drugs, the nanoformulations significantly reduced cell viability, increased apoptosis, and induced cell-cycle arrest. Functionalization with ligands such as folic acid enhanced drug targeting and cytotoxicity, while the molecular analyses revealed upregulation of p53, Bax, and caspases as well as downregulation of Bcl-2 and hTERT genes. Conclusion: PEG–PLGA nanoparticles can substantially improve the selectivity, bioavailability, and cytotoxic efficacies of anticancer drugs in breast cancer in vitro . These findings underscore their translational potential as next-generation drug-delivery systems, warranting in vivo validation as well as development of theranostic- and stimulus-responsive designs for personalized oncology. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076570 .
- 5 January 2026
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 16, 1710176
Open AccessEffectiveness of drug-loaded poly(ethylene glycol) and poly(lactic-co-glycolic-acid) nanoparticles in the in vitro treatment of breast cancer: a systematic review
Background: Breast cancer treatment remains a major challenge to modern medicine and has driven the need for nanotechnology-based strategies to improve drug delivery and overcome chemoresistance. Poly(ethylene glycol) and poly (lactic-co-glycolic acid) (PEG–PLGA) nanoparticles (NPs) are a type of FDA-approved biodegradable copolymer (lactic + glycolic acids) that degrades into non-toxic metabolites (lactic acid and glycolic acid); it has emerged as a promising drug carrier owing to its biocompatibility, sustained release properties, and ability to enhance the cellular uptake of chemotherapeutic agents. This systematic review examines the efficacies of PEG–PLGA nanoparticles loaded with antineoplastic drugs on in vitro models of breast cancer cell lines. Methods: Following PRISMA guidelines, we conducted a comprehensive search of the Web of Science, Embase, MEDLINE, and Scopus databases to identify experimental studies published between 2014 and August 2025 that evaluated PEG–PLGA formulations applied to breast cancer cell lines. The methodological quality of each study was appraised using the National Institute for Health and Care Excellence (NICE) criteria. Results: Thirteen studies were chosen based on our inclusion criteria. Here, the PEG–PLGA nanoparticles were predominantly spherical (30–210 nm) and exhibited controlled release kinetics. Compared with free drugs, the nanoformulations significantly reduced cell viability, increased apoptosis, and induced cell-cycle arrest. Functionalization with ligands such as folic acid enhanced drug targeting and cytotoxicity, while the molecular analyses revealed upregulation of p53, Bax, and caspases as well as downregulation of Bcl-2 and hTERT genes. Conclusion: PEG–PLGA nanoparticles can substantially improve the selectivity, bioavailability, and cytotoxic efficacies of anticancer drugs in breast cancer in vitro . These findings underscore their translational potential as next-generation drug-delivery systems, warranting in vivo validation as well as development of theranostic- and stimulus-responsive designs for personalized oncology. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076570 .
- 27 December 2025
- Published by Wiley in Journal of the American Geriatrics Society
- Vol. 74 (2) , 313-315
Mindfulness, Cognition, and Emotional Health in Aging: Beyond the Mind to the Neurobiology of Adaptation
- 27 December 2025
- Published by Wiley in Journal of the American Geriatrics Society
- Vol. 74 (2) , 313-315
Mindfulness, Cognition, and Emotional Health in Aging: Beyond the Mind to the Neurobiology of Adaptation
- Open Access
- 14 November 2025
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 26 (22) , 11036
Mild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes
Mild cognitive impairment (MCI) and sarcopenia are prevalent age-related conditions that often coexist and share common mechanisms such as chronic inflammation, reduced neuroplasticity, and impaired muscle function. Resistance exercise training (RET) has emerged as a promising non-pharmacological strategy capable of addressing both physical and cognitive decline. The aim of this narrative review is to synthesize preclinical and clinical evidence on the effects of RET in older adults with MCI and sarcopenia, with a specific focus on its impact on neuroinflammation, cognitive performance and structural brain changes. At the molecular level, RET activates anabolic pathways, including PI3K/Akt/mTOR, enhances neurotrophic support via BDNF, NT-3, and IGF-1, and promotes hippocampal neurogenesis through exercise-induced myokines such as irisin and cathepsin B. RET also exerts immunomodulatory actions by shifting microglia toward anti-inflammatory M2 phenotypes, attenuating reactive astrogliosis, and supporting oligodendrocyte precursor cell differentiation, thereby improving myelin integrity. Neuroimaging studies consistently report preservation of hippocampal and precuneus gray matter, as well as improved white matter connectivity following RET. Clinically, RET has demonstrated significant and sustained improvements in executive function, memory, and global cognition, with effects persisting for up to 18 months. Collectively, RET represents a multifaceted intervention with the potential to delay progression from MCI to Alzheimer’s disease by integrating neuroprotective, anti-inflammatory, and anabolic effects. Standardization of RET protocols and identification of biomarkers of responsiveness are needed to optimize its role within multimodal dementia-prevention strategies.
- 14 November 2025
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 26 (22) , 11036
Open AccessMild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes
Mild cognitive impairment (MCI) and sarcopenia are prevalent age-related conditions that often coexist and share common mechanisms such as chronic inflammation, reduced neuroplasticity, and impaired muscle function. Resistance exercise training (RET) has emerged as a promising non-pharmacological strategy capable of addressing both physical and cognitive decline. The aim of this narrative review is to synthesize preclinical and clinical evidence on the effects of RET in older adults with MCI and sarcopenia, with a specific focus on its impact on neuroinflammation, cognitive performance and structural brain changes. At the molecular level, RET activates anabolic pathways, including PI3K/Akt/mTOR, enhances neurotrophic support via BDNF, NT-3, and IGF-1, and promotes hippocampal neurogenesis through exercise-induced myokines such as irisin and cathepsin B. RET also exerts immunomodulatory actions by shifting microglia toward anti-inflammatory M2 phenotypes, attenuating reactive astrogliosis, and supporting oligodendrocyte precursor cell differentiation, thereby improving myelin integrity. Neuroimaging studies consistently report preservation of hippocampal and precuneus gray matter, as well as improved white matter connectivity following RET. Clinically, RET has demonstrated significant and sustained improvements in executive function, memory, and global cognition, with effects persisting for up to 18 months. Collectively, RET represents a multifaceted intervention with the potential to delay progression from MCI to Alzheimer’s disease by integrating neuroprotective, anti-inflammatory, and anabolic effects. Standardization of RET protocols and identification of biomarkers of responsiveness are needed to optimize its role within multimodal dementia-prevention strategies.
- Open Access
- 9 October 2025
- Published by Frontiers Media SA in Frontiers in Medicine
- Vol. 12, 1659208
Effects of non-invasive brain stimulation combined with cognitive training on cognitive functions in older people with mild cognitive impairment: a systematic review with meta-analysis
Background: Non-invasive brain stimulation (NIBS) has emerged as a potential adjunct to cognitive training for enhancing cognitive performance in older peoples with mild cognitive impairment (MCI). This systematic review and meta-analysis aimed to evaluate the efficacy of combined NIBS and cognitive training on cognitive function in this population.Methods: A comprehensive literature search was conducted in PubMed, EBSCOhost, CINAHL Complete, Cochrane Library, ProQuest, Scopus, and Web of Science up to May 2025. The review followed PRISMA guidelines, and methodological quality was assessed using the Oxford Centre for Evidence-Based Medicine levels, the Cochrane Risk of Bias 2 tool (RoB 2) tool for risk of bias, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for the certainty of evidence. The protocol was registered in PROSPERO (CRD42024563219). Studies were included if they assessed the effects of NIBS in combination with cognitive training on cognitive outcomes in older peoples with MCI.Results: A total of 1,689 records were screened, and 10 studies met the inclusion criteria. The results indicated a moderate positive effect of the combined intervention on attention and processing speed as measured by the Trail-Making Test Part A (TMT-A; effect size = 0.54). Improvements were also observed in global cognition as assessed by the Montreal Cognitive Assessment (MoCA), though the results were not statistically significant (p > 0.05). No significant effects were found for the Trail-Making Test Part B (TMT-B), with effect sizes ranging from 0.05 to 0.52.Conclusion: The combination of NIBS and cognitive training appears to yield beneficial effects on specific cognitive domains, particularly attention and processing speed, in older people with MCI. These findings support the potential role of NIBS as an adjunctive intervention to cognitive training for enhancing cognitive function in this population. Further high-quality randomized controlled trials are warranted to confirm these effects.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563219, identifier (CRD42024563219).
- 9 October 2025
- Published by Frontiers Media SA in Frontiers in Medicine
- Vol. 12, 1659208
Open AccessEffects of non-invasive brain stimulation combined with cognitive training on cognitive functions in older people with mild cognitive impairment: a systematic review with meta-analysis
Background: Non-invasive brain stimulation (NIBS) has emerged as a potential adjunct to cognitive training for enhancing cognitive performance in older peoples with mild cognitive impairment (MCI). This systematic review and meta-analysis aimed to evaluate the efficacy of combined NIBS and cognitive training on cognitive function in this population.Methods: A comprehensive literature search was conducted in PubMed, EBSCOhost, CINAHL Complete, Cochrane Library, ProQuest, Scopus, and Web of Science up to May 2025. The review followed PRISMA guidelines, and methodological quality was assessed using the Oxford Centre for Evidence-Based Medicine levels, the Cochrane Risk of Bias 2 tool (RoB 2) tool for risk of bias, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for the certainty of evidence. The protocol was registered in PROSPERO (CRD42024563219). Studies were included if they assessed the effects of NIBS in combination with cognitive training on cognitive outcomes in older peoples with MCI.Results: A total of 1,689 records were screened, and 10 studies met the inclusion criteria. The results indicated a moderate positive effect of the combined intervention on attention and processing speed as measured by the Trail-Making Test Part A (TMT-A; effect size = 0.54). Improvements were also observed in global cognition as assessed by the Montreal Cognitive Assessment (MoCA), though the results were not statistically significant (p > 0.05). No significant effects were found for the Trail-Making Test Part B (TMT-B), with effect sizes ranging from 0.05 to 0.52.Conclusion: The combination of NIBS and cognitive training appears to yield beneficial effects on specific cognitive domains, particularly attention and processing speed, in older people with MCI. These findings support the potential role of NIBS as an adjunctive intervention to cognitive training for enhancing cognitive function in this population. Further high-quality randomized controlled trials are warranted to confirm these effects.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563219, identifier (CRD42024563219).
- Open Access
Effects of Different Interventions Using Taekwondo, Boxing, and Elastic Band Training on Body Composition and Physical Function in Chilean Older Women: A Randomized Controlled Trial
Background: Interventions involving Olympic combat sports, such as Taekwondo (TKD) and Boxing (BOX), represent innovative approaches for promoting health in older people. Elastic bands training (EBT), by contrast, is a safe and cost-effective method that has demonstrated positive effects on functional physical parameters in this population. This study aimed to compare the effects of TKD and BOX interventions, relative to EBT, on body composition and physical function in Chilean older women. Methods: This randomized controlled trial comprised three parallel groups: TKD (n = 10), BOX (n = 10), and EBT (n = 10). Participants in each group underwent pre- and post-intervention assessments following two 60 min sessions per week over an eight-week period. Results: Multiple comparisons revealed significant advantages for EBT over TKD and BOX in maximal isometric handgrip strength for both the dominant (p < 0.001; d = 0.967, large effect) and non-dominant (p < 0.001; d = 0.641, moderate effect) hands. Conversely, significant improvements in Timed Up-and-Go performance were observed in the TKD and BOX groups compared to EBT (p < 0.001; d = 2.071, large effect). All groups showed significant within-group improvements in the 30 s chair stand test (p < 0.001; d = 0.095, large effect). No significant changes were found in body fat percentage, fat-free mass, back scratch test, sit-and-reach test, or 2 min step test across groups. Conclusions: Although no substantial differences were observed between groups for most variables, TKD and BOX interventions significantly reduced Timed Up-and-Go times, whereas EBT enhanced maximal isometric handgrip strength in both hands. These findings highlight the distinct functional benefits of each intervention modality for older Chilean women.
Open AccessEffects of Different Interventions Using Taekwondo, Boxing, and Elastic Band Training on Body Composition and Physical Function in Chilean Older Women: A Randomized Controlled Trial
Background: Interventions involving Olympic combat sports, such as Taekwondo (TKD) and Boxing (BOX), represent innovative approaches for promoting health in older people. Elastic bands training (EBT), by contrast, is a safe and cost-effective method that has demonstrated positive effects on functional physical parameters in this population. This study aimed to compare the effects of TKD and BOX interventions, relative to EBT, on body composition and physical function in Chilean older women. Methods: This randomized controlled trial comprised three parallel groups: TKD (n = 10), BOX (n = 10), and EBT (n = 10). Participants in each group underwent pre- and post-intervention assessments following two 60 min sessions per week over an eight-week period. Results: Multiple comparisons revealed significant advantages for EBT over TKD and BOX in maximal isometric handgrip strength for both the dominant (p < 0.001; d = 0.967, large effect) and non-dominant (p < 0.001; d = 0.641, moderate effect) hands. Conversely, significant improvements in Timed Up-and-Go performance were observed in the TKD and BOX groups compared to EBT (p < 0.001; d = 2.071, large effect). All groups showed significant within-group improvements in the 30 s chair stand test (p < 0.001; d = 0.095, large effect). No significant changes were found in body fat percentage, fat-free mass, back scratch test, sit-and-reach test, or 2 min step test across groups. Conclusions: Although no substantial differences were observed between groups for most variables, TKD and BOX interventions significantly reduced Timed Up-and-Go times, whereas EBT enhanced maximal isometric handgrip strength in both hands. These findings highlight the distinct functional benefits of each intervention modality for older Chilean women.
- Open Access
Thyroid Hormone Supplementation Restores Cognitive Deficit, Insulin Signaling, and Neuroinflammation in the Hippocampus of a Sporadic Alzheimer’s-like Disease Rat Model
Thyroid hormones play a crucial role in the development of the central nervous system and are considered pivotal to cognitive functions in the adult brain. Recently, thyroid dysfunction has been associated with Alzheimer’s disease. The aim of this study was to assess the neuroprotective effects of triiodothyronine (T3) on insulin signaling, neuroinflammation, apoptosis, and cognitive function in a streptozotocin (STZ)-induced sporadic Alzheimer’s disease-like model. Male Wistar rats underwent stereotaxic surgery for intracerebroventricular injections of streptozotocin (STZ; 2 mg/kg) or vehicle in the lateral ventricles to induce an AD-like model. The animals received a daily dose of 1.5 μg of T3/100 g body weight or the same volume of vehicle for 30 days and were subdivided into four experimental groups: (1) animals receiving citrate treated with saline (Control = CTL); (2) animals receiving citrate treated with T3 (T3); (3) animals receiving STZ treated with saline (STZ); and (4) animals receiving STZ treated with T3 (STZ + T3). The novel object recognition test was used to measure cognitive function. Serum analysis, real-time RT-PCR, immunohistochemistry, and immunoblotting analyses were also carried out. Our results demonstrated that T3 treatment reversed cognitive impairment and increased Akt and GSK3 phosphorylation in the treated group, while also reducing microglial activation (Iba-1) and GFAP expression (reactive astrocytes), along with TNF-α, IL-6, and IL-1β levels in the hippocampus. Additionally, T3 treatment increased levels of the anti-apoptotic protein Bcl-2 and reduced the expression of the pro-apoptotic protein BAX in the hippocampus. Our study demonstrated that T3 could potentially protect neurons in an AD model induced by STZ.
Open AccessThyroid Hormone Supplementation Restores Cognitive Deficit, Insulin Signaling, and Neuroinflammation in the Hippocampus of a Sporadic Alzheimer’s-like Disease Rat Model
Thyroid hormones play a crucial role in the development of the central nervous system and are considered pivotal to cognitive functions in the adult brain. Recently, thyroid dysfunction has been associated with Alzheimer’s disease. The aim of this study was to assess the neuroprotective effects of triiodothyronine (T3) on insulin signaling, neuroinflammation, apoptosis, and cognitive function in a streptozotocin (STZ)-induced sporadic Alzheimer’s disease-like model. Male Wistar rats underwent stereotaxic surgery for intracerebroventricular injections of streptozotocin (STZ; 2 mg/kg) or vehicle in the lateral ventricles to induce an AD-like model. The animals received a daily dose of 1.5 μg of T3/100 g body weight or the same volume of vehicle for 30 days and were subdivided into four experimental groups: (1) animals receiving citrate treated with saline (Control = CTL); (2) animals receiving citrate treated with T3 (T3); (3) animals receiving STZ treated with saline (STZ); and (4) animals receiving STZ treated with T3 (STZ + T3). The novel object recognition test was used to measure cognitive function. Serum analysis, real-time RT-PCR, immunohistochemistry, and immunoblotting analyses were also carried out. Our results demonstrated that T3 treatment reversed cognitive impairment and increased Akt and GSK3 phosphorylation in the treated group, while also reducing microglial activation (Iba-1) and GFAP expression (reactive astrocytes), along with TNF-α, IL-6, and IL-1β levels in the hippocampus. Additionally, T3 treatment increased levels of the anti-apoptotic protein Bcl-2 and reduced the expression of the pro-apoptotic protein BAX in the hippocampus. Our study demonstrated that T3 could potentially protect neurons in an AD model induced by STZ.
- Open Access
- 27 June 2024
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 25 (13) , 7084
Resistance Exercise Training as a New Trend in Alzheimer’s Disease Research: From Molecular Mechanisms to Prevention
Alzheimer’s disease is a pathology characterized by the progressive loss of neuronal connections, which leads to gray matter atrophy in the brain. Alzheimer’s disease is the most prevalent type of dementia and has been classified into two types, early onset, which has been associated with genetic factors, and late onset, which has been associated with environmental factors. One of the greatest challenges regarding Alzheimer’s disease is the high economic cost involved, which is why the number of studies aimed at prevention and treatment have increased. One possible approach is the use of resistance exercise training, given that it has been shown to have neuroprotective effects associated with Alzheimer’s disease, such as increasing cortical and hippocampal volume, improving neuroplasticity, and promoting cognitive function throughout the life cycle. However, how resistance exercise training specifically prevents or ameliorates Alzheimer’s disease has not been fully characterized. Therefore, the aim of this review was to identify the molecular basis by which resistance exercise training could prevent or treat Alzheimer’s disease.
- 27 June 2024
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 25 (13) , 7084
Open AccessResistance Exercise Training as a New Trend in Alzheimer’s Disease Research: From Molecular Mechanisms to Prevention
Alzheimer’s disease is a pathology characterized by the progressive loss of neuronal connections, which leads to gray matter atrophy in the brain. Alzheimer’s disease is the most prevalent type of dementia and has been classified into two types, early onset, which has been associated with genetic factors, and late onset, which has been associated with environmental factors. One of the greatest challenges regarding Alzheimer’s disease is the high economic cost involved, which is why the number of studies aimed at prevention and treatment have increased. One possible approach is the use of resistance exercise training, given that it has been shown to have neuroprotective effects associated with Alzheimer’s disease, such as increasing cortical and hippocampal volume, improving neuroplasticity, and promoting cognitive function throughout the life cycle. However, how resistance exercise training specifically prevents or ameliorates Alzheimer’s disease has not been fully characterized. Therefore, the aim of this review was to identify the molecular basis by which resistance exercise training could prevent or treat Alzheimer’s disease.
- Open Access
- 4 February 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (4) , 3073
Relationship between Hypoxic and Immune Pathways Activation in the Progression of Neuroinflammation: Role of HIF-1α and Th17 Cells
Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. This review propounds the relationship between the deregulation of T helper cells and hypoxia, mainly Th17 and HIF-1α molecular pathways, events that are involved in the occurrence of the neuroinflammation. The clinical expression of neuroinflammation is included in prevalent pathologies such as multiple sclerosis, Guillain–Barré syndrome, and Alzheimer’s disease, among others. In addition, therapeutic targets are analyzed in relation to the pathways that induced neuroinflammation.
- 4 February 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (4) , 3073
Open AccessRelationship between Hypoxic and Immune Pathways Activation in the Progression of Neuroinflammation: Role of HIF-1α and Th17 Cells
Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. This review propounds the relationship between the deregulation of T helper cells and hypoxia, mainly Th17 and HIF-1α molecular pathways, events that are involved in the occurrence of the neuroinflammation. The clinical expression of neuroinflammation is included in prevalent pathologies such as multiple sclerosis, Guillain–Barré syndrome, and Alzheimer’s disease, among others. In addition, therapeutic targets are analyzed in relation to the pathways that induced neuroinflammation.