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1.
BMC Neurosci ; 22(1): 28, 2021 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-33882822

RESUMEN

BACKGROUND: Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis. RESULTS: We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10. CONCLUSIONS: The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.


Asunto(s)
Encéfalo/efectos de la radiación , Irradiación Craneana/efectos adversos , Neurogénesis/efectos de la radiación , Animales , Animales Recién Nacidos , Encéfalo/crecimiento & desarrollo , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C
2.
Int J Mol Sci ; 21(24)2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327654

RESUMEN

The hippocampus is crucial in learning, memory and emotion processing, and is involved in the development of different neurological and neuropsychological disorders. Several epigenetic factors, including DNA methylation, histone modifications and non-coding RNAs, have been shown to regulate the development and function of the hippocampus, and the alteration of epigenetic regulation may play important roles in the development of neurocognitive and neurodegenerative diseases. This review summarizes the epigenetic modifications of various cell types and processes within the hippocampus and their resulting effects on cognition, memory and overall hippocampal function. In addition, the effects of exposure to radiation that may induce a myriad of epigenetic changes in the hippocampus are reviewed. By assessing and evaluating the current literature, we hope to prompt a more thorough understanding of the molecular mechanisms that underlie radiation-induced epigenetic changes, an area which can be further explored.


Asunto(s)
Epigénesis Genética/fisiología , Hipocampo/metabolismo , Animales , Metilación de ADN/genética , Metilación de ADN/fisiología , Epigénesis Genética/genética , Histonas/metabolismo , Humanos , MicroARNs/metabolismo , Neuroglía/citología , Neuroglía/metabolismo
3.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32041250

RESUMEN

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1ß, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.


Asunto(s)
Prepucio/citología , Rayos gamma/efectos adversos , Queratinocitos/citología , Protectores contra Radiación/farmacología , Triterpenos/farmacología , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Modelos Animales de Enfermedad , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Fibroblastos/efectos de la radiación , Prepucio/efectos de los fármacos , Prepucio/inmunología , Prepucio/efectos de la radiación , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Glutatión/efectos de la radiación , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/inmunología , Queratinocitos/efectos de la radiación , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Triterpenos Pentacíclicos , Factor de Necrosis Tumoral alfa/metabolismo
4.
J Cell Biochem ; 120(3): 4504-4513, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30260018

RESUMEN

Oleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)-negative breast cancer is not fully understood. This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER-negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by flow cytometric analysis, nuclear factor-κB (NF-κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA-MB-231 as compared with MCF-7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF-κB was abrogated as demonstrated by Western blot analysis, NF-κB-DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF-κB activation cascade in breast cancer cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Iridoides/farmacología , FN-kappa B/metabolismo , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Glucósidos Iridoides , Células MCF-7
5.
Pharmacol Res ; 133: 195-200, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29758279

RESUMEN

Genipin, an aglycone derived from the iridoid glycoside, geniposide, is isolated and characterized from the extract of Gardenia jasminoides Ellis fruit (family Rubiaceae). It has long been used in traditional oriental medicine for the prevention and treatment of several inflammation driven diseases, including cancer. Genipin has been shown to have hepatoprotective activity acting as a potent antioxidant and inhibitor of mitochondrial uncoupling protein 2 (UCP2), and also reported to exert significant anticancer effects. It is an excellent crosslinking agent that helps to make novel sustained or delayed release nanoparticle formulations. In this review, we present the latest developments of genipin as an anticancer agent and briefly describe its diverse mechanism(s) of action. Several lines of evidence suggest that genipin is a potent inhibitor of UCP2, which functions as a tumor promoter in a variety of cancers, attenuates generation of reactive oxygen species and the expression of matrix metalloproteinase 2, as well as induces caspase-dependent apoptosis in vitro and in in vivo models. These finding suggests that genipin can serve as both a prominent anticancer agent as well as a potent crosslinking drug that may find useful application in several novel pharmaceutical formulations.


Asunto(s)
Antineoplásicos/uso terapéutico , Reactivos de Enlaces Cruzados/uso terapéutico , Iridoides/uso terapéutico , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Reactivos de Enlaces Cruzados/farmacología , Humanos , Iridoides/farmacología
6.
Int J Mol Sci ; 19(9)2018 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-30213136

RESUMEN

As an important second messenger, the calcium ion (Ca2+) plays a vital role in normal brain function and in the pathophysiological process of different neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and epilepsy. Ca2+ takes part in the regulation of neuronal excitability, and the imbalance of intracellular Ca2+ is a trigger factor for the occurrence of epilepsy. Several anti-epileptic drugs target voltage-dependent calcium channels (VDCCs). Intracellular Ca2+ levels are mainly controlled by VDCCs located in the plasma membrane, the calcium-binding proteins (CBPs) inside the cytoplasm, calcium channels located on the intracellular calcium store (particular the endoplasmic reticulum/sarcoplasmic reticulum), and the Ca2+-pumps located in the plasma membrane and intracellular calcium store. So far, while many studies have established the relationship between calcium control factors and epilepsy, the mechanism of various Ca2+ regulatory factors in epileptogenesis is still unknown. In this paper, we reviewed the function, distribution, and alteration of VDCCs and CBPs in the central nervous system in the pathological process of epilepsy. The interaction of VDCCs with CBPs in the pathological process of epilepsy was also summarized. We hope this review can provide some clues for better understanding the mechanism of epileptogenesis, and for the development of new anti-epileptic drugs targeting on VDCCs and CBPs.


Asunto(s)
Canales de Calcio/metabolismo , Proteínas de Unión al Calcio/metabolismo , Epilepsia/metabolismo , Animales , Calcio/metabolismo , Señalización del Calcio , Humanos
7.
Curr Neurol Neurosci Rep ; 16(2): 20, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26769029

RESUMEN

The mobilization of endogenous neural stem cells in order to substitute lost neurons in the adult brain may reduce the negative effects of patients with chronic neurodegenerative diseases. However, abnormal neurogenesis may be harmful and could lead to the worsening of patients' symptoms. In the brains of patients and animal models with temporal lobe epilepsy (TLE), increased newly generated neurons in the subgranular zone (SGZ) at early stages after brain insults have been speculated to be involved in epileptogenesis. However, this argument is unsupported by evidence showing that (1) hippocampal neurogenesis is reduced at chronic stages of intractable TLE, (2) decreased neurogenesis is involved in epileptogenesis, and (3) spontaneous recurrent seizures occur before newly generated neurons are integrated into hippocampal neural pathways. Therefore, the hypothesis of increased neurogenesis in epileptogenesis may need to be re-evaluated. In this paper, we systemically reviewed brain neurogenesis and relevant molecules in the regulation of neurogenesis in SGZ. We aimed to update researchers and epileptologists on current progresses on pathophysiological changes of neurogenesis at different stages of TLE in patients and animal models of TLE. The interactions among neurogenesis, epileptogenesis and cognitive impairment, and molecules' mechanism involved in neurogenesis would also be discussed. Future research directions are proposed at the end of this paper.


Asunto(s)
Epilepsia del Lóbulo Temporal , Hipocampo , Neurogénesis , Trastornos del Conocimiento/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Humanos , Células-Madre Neurales , Neuronas/fisiología , Convulsiones/fisiopatología
9.
Radiat Res ; 202(4): 677-684, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39164012

RESUMEN

The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.


Asunto(s)
Giro Dentado , MicroARNs , Neuronas , Tolerancia a Radiación , Animales , MicroARNs/genética , MicroARNs/metabolismo , Giro Dentado/efectos de la radiación , Giro Dentado/metabolismo , Ratones , Tolerancia a Radiación/genética , Neuronas/efectos de la radiación , Neuronas/metabolismo , Apoptosis/efectos de la radiación , Masculino , Ratones Endogámicos C57BL
10.
Cells ; 13(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39272995

RESUMEN

Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (<6 mGy/h) with accumulative low (≤100 mGy) or high (>100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- and/or post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight, pathological, and blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction (qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes, including immature neurons in the subgranular zone, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders, occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weights showed significant reductions in the testes, kidneys, heart, liver and epididymides with no abnormal pathology. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl and Abhd14b, and downregulation of Hspa1b, P4ha1, and Banp genes in both the hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p and miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b, and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8 Gy or below might not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposures with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or spending once a nuclear accident or leakage occurs.


Asunto(s)
Hipocampo , MicroARNs , Efectos Tardíos de la Exposición Prenatal , ARN Mensajero , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratones , Hipocampo/efectos de la radiación , Hipocampo/metabolismo , Hipocampo/patología , Femenino , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Masculino , Conducta Animal/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Tamaño de los Órganos/efectos de la radiación
11.
Front Biosci (Landmark Ed) ; 28(2): 38, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36866558

RESUMEN

Ischemic stroke and cranial radiotherapy may induce brain inflammatory response, oxidative stress, apoptosis and neuronal loss, and impairment of neurogenesis. Lycium barbarum has anti-oxidation, anti-inflammatory, anti-tumor and anti-aging properties, may produce both neuroprotective and radioprotective effects. In this narrative review paper, we described the neuroprotective effect of Lycium barbarum in different animal models of experimental ischemic stroke and limited studies in irradiated animal models. Relevant molecular mechanisms are also summarized. It has been shown that in experimental ischemic stroke models, Lycium barbarum produces neuroprotective effects by modulating neuroinflammatory factors such as cytokines and chemokines, reactive oxygen species, and neurotransmitter and receptor systems. In irradiation animal models, Lycium barbarum prevents radiation-induced loss of hippocampal interneurons. Given its minimal side-effects, these preclinical studies suggest that Lycium barbarum may be a promising radio-neuro-protective drug that can be used as an adjunct treatment to radiotherapy for brain tumor and in the treatment of ischemic stroke. At molecular levels, Lycium barbarum may regulate PI3K/Akt/GSK-3ß, PI3K/Akt/mTOR, PKCε/Nrf2/HO-1, keap1-Nrf2/HO-1, and NR2A and NR2B receptor- related signal transduction pathways to produce neuroprotective effects.


Asunto(s)
Accidente Cerebrovascular Isquémico , Lycium , Fármacos Neuroprotectores , Exposición a la Radiación , Animales , Glucógeno Sintasa Quinasa 3 beta , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Fármacos Neuroprotectores/farmacología , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt
12.
Cells ; 12(4)2023 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-36831315

RESUMEN

Ionizing radiation induces brain inflammation and the impairment of neurogenesis by activating microglia and inducing apoptosis in neurogenic zones. However, the causal relationship between microglial activation and the impairment of neurogenesis as well as the relevant molecular mechanisms involved in microRNA (miR) remain unknown. In the present study, we employed immunohistochemistry and real-time RT-PCR to study the microglial activation and miRNA expression in mouse brains. Real-time RT-PCR, western blot, ELISA, cell proliferation and cytotoxicity assay were used in BV2 and mouse neural stem cells (NSCs). In the mouse model, we found the acute activation of microglia at 1 day and an increased number of microglial cells at 1, 7 and 120 days after irradiation at postnatal day 3 (P3), day 10 (P10) and day 21 (P21), respectively. In cell models, the activation of BV2, a type of microglial cell line, was observed after gamma irradiation. Real-time RT-PCR analysis revealed a deceased expression of miR-181b-2-3p and an increased expression of its target SRY-related high-mobility group box transcription factor 21 (SOX21) in a dose- and time-dependent fashion. The results of the luciferase reporter assay confirmed that SOX21 was the target of miR-181b-2-3p. Furthermore, SOX21 knockdown by siRNA inhibited the activation of microglia, thereby suggesting that the direct interaction of 181b-2-3p with SOX21 might be involved in radiation-induced microglial activation and proliferation. Interestingly, the gamma irradiation of NSCs increased miR-181b-2-3p expression but decreased SOX21 mRNA, which was the opposite of irradiation-induced expression in BV2 cells. As irradiation reduced the viability and proliferation of NSCs, whereas the overexpression of SOX21 restored the impaired cell viability and promoted the proliferation of NSCs, the findings suggest that the radiation-induced interaction of miR-181b-2-3p with SOX21 may play dual roles in microglia and NSCs, respectively, leading to the impairment of brain neurogenesis.


Asunto(s)
MicroARNs , Células-Madre Neurales , Ratones , Animales , Microglía/metabolismo , MicroARNs/genética , Línea Celular , ARN Interferente Pequeño/metabolismo , Células-Madre Neurales/metabolismo
13.
Biomolecules ; 13(5)2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-37238624

RESUMEN

The neuron loss caused by the progressive damage to the nervous system is proposed to be the main pathogenesis of neurodegenerative diseases. Ependyma is a layer of ciliated ependymal cells that participates in the formation of the brain-cerebrospinal fluid barrier (BCB). It functions to promotes the circulation of cerebrospinal fluid (CSF) and the material exchange between CSF and brain interstitial fluid. Radiation-induced brain injury (RIBI) shows obvious impairments of the blood-brain barrier (BBB). In the neuroinflammatory processes after acute brain injury, a large amount of complement proteins and infiltrated immune cells are circulated in the CSF to resist brain damage and promote substance exchange through the BCB. However, as the protective barrier lining the brain ventricles, the ependyma is extremely vulnerable to cytotoxic and cytolytic immune responses. When the ependyma is damaged, the integrity of BCB is destroyed, and the CSF flow and material exchange is affected, leading to brain microenvironment imbalance, which plays a vital role in the pathogenesis of neurodegenerative diseases. Epidermal growth factor (EGF) and other neurotrophic factors promote the differentiation and maturation of ependymal cells to maintain the integrity of the ependyma and the activity of ependymal cilia, and may have therapeutic potential in restoring the homeostasis of the brain microenvironment after RIBI or during the pathogenesis of neurodegenerative diseases.


Asunto(s)
Lesiones Encefálicas , Enfermedades Neurodegenerativas , Humanos , Epéndimo/metabolismo , Epéndimo/patología , Factores de Crecimiento Nervioso/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo
14.
Crit Rev Toxicol ; 42(8): 688-702, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22742653

RESUMEN

Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.


Asunto(s)
Bronquiolitis Obliterante/fisiopatología , Sustancias para la Guerra Química/toxicidad , Neoplasias Pulmonares/fisiopatología , Gas Mostaza/toxicidad , Fibrosis Pulmonar/fisiopatología , Sistema Respiratorio/efectos de los fármacos , Animales , Bronquiolitis Obliterante/etiología , Modelos Animales de Enfermedad , Selectina E/metabolismo , Glutatión/metabolismo , Humanos , Irán , Irak , Neoplasias Pulmonares/etiología , Óxido Nítrico Sintasa/metabolismo , Ácido Peroxinitroso/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Fibrosis Pulmonar/etiología , Primera Guerra Mundial
15.
Int J Radiat Biol ; 98(10): 1519-1531, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35311621

RESUMEN

PURPOSE: With technological advancements in radiation therapy for tumors of the central nervous system (CNS), high doses of ionizing radiation can be delivered to the tumors with improved accuracy. Despite the reduction of ionizing radiation-induced toxicity to surrounding tissues of the CNS, a wide array of side effects still occurs, particularly late-delayed changes. These alterations, such as white matter damages and neurocognitive impairments, are often debilitative and untreatable, significantly affecting the quality of life of these patients, especially children. Oligodendrocytes, a major class of glial cells, have been identified to be one of the targets of radiation toxicity and are recognized be involved in late-delayed radiation-induced neuropathological changes. These cells are responsible for forming the myelin sheaths that surround and insulate axons within the CNS. Here, the effects of ionizing radiation on the oligodendrocyte lineage as well as the common clinical manifestations resulting from radiation-induced damage to oligodendrocytes will be discussed. Potential prophylactic and therapeutic strategies against radiation-induced oligodendrocyte damage will also be considered. CONCLUSION: Oligodendrocytes and oligodendrocyte progenitor cells (OPCs) are radiosensitive cells of the CNS. Here, general responses of these cells to radiation exposure have been outlined. However, several findings have not been consistent across various studies. For instance, cognitive decline in irradiated animals was observed to be accompanied by obvious demyelination or white matter changes in several studies but not in others. Hence, further studies have to be conducted to elucidate the level of contribution of the oligodendrocyte lineage to the development of late-delayed effects of radiation exposure, as well as to classify the dose and brain region-specific responses of the oligodendrocyte lineage to radiation. Several potential therapeutic approaches against late-delayed changes have been discussed, such as the transplantation of OPCs into irradiated regions and implementation of exercise. Many of these approaches show promising results. Further elucidation of the mechanisms involved in radiation-induced death of oligodendrocytes and OPCs would certainly aid in the development of novel protective and therapeutic strategies against the late-delayed effects of radiation.


Asunto(s)
Oligodendroglía , Calidad de Vida , Animales , Diferenciación Celular , Linaje de la Célula , Sistema Nervioso Central , Vaina de Mielina , Oligodendroglía/patología , Oligodendroglía/fisiología
16.
Aging (Albany NY) ; 14(3): 1562-1588, 2022 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-35165207

RESUMEN

Epimedium brevicornum Maxim, a Traditional Chinese Medicine, has been used for the treatment of impotence, sinew and bone disorders, "painful impediment caused by wind-dampness," numbness, spasms, hypertension, coronary heart disease, menopausal syndrome, bronchitis, and neurasthenia for many years in China. Recent animal experimental studies indicate that icariin, a major bioactive component of epimedium may effectively treat Alzheimer's disease, cerebral ischemia, depression, Parkinson's disease, multiple sclerosis, as well as delay ageing. Our recent study also suggested that epimedium extract could exhibit radio-neuro-protective effects and prevent ionizing radiation-induced impairment of neurogenesis. This paper reviewed the pharmacodynamics of icariin in treating different neurodegenerative and neuropsychiatric diseases, ageing, and radiation-induced brain damage. The relevant molecular mechanisms and its anti-neuroinflammatory, anti-apoptotic, anti-oxidant, as well as pro-neurogenesis roles were also discussed.


Asunto(s)
Lesiones Encefálicas , Epimedium , Fármacos Neuroprotectores , Exposición a la Radiación , Envejecimiento , Animales , Flavonoides/farmacología , Flavonoides/uso terapéutico , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico
17.
Curr Med Chem ; 28(1): 19-52, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31965936

RESUMEN

Radiation exposure may induce Alzheimer's disease (AD), depression or schizophrenia. A number of experimental and clinical studies suggest the involvement of miRNA in the development of these diseases, and also in the neuropathological changes after brain radiation exposure. The current literature review indicated the involvement of 65 miRNAs in neuronal development in the brain. In the brain tissue, blood, or cerebral spinal fluid (CSF), 11, 55, or 28 miRNAs are involved in the development of AD respectively, 89, 50, 19 miRNAs in depression, and 102, 35, 8 miRNAs in schizophrenia. We compared miRNAs regulating neuronal development to those involved in the genesis of AD, depression and schizophrenia and also those driving radiation-induced brain neuropathological changes by reviewing the available data. We found that 3, 11, or 8 neuronal developmentrelated miRNAs from the brain tissue, 13, 16 or 14 miRNAs from the blood of patient with AD, depression and schizophrenia respectively were also involved in radiation-induced brain pathological changes, suggesting a possibly specific involvement of these miRNAs in radiation-induced development of AD, depression and schizophrenia respectively. On the other hand, we noted that radiationinduced changes of two miRNAs, i.e., miR-132, miR-29 in the brain tissue, three miRNAs, i.e., miR- 29c-5p, miR-106b-5p, miR-34a-5p in the blood were also involved in the development of AD, depression and schizophrenia, thereby suggesting that these miRNAs may be involved in the common brain neuropathological changes, such as impairment of neurogenesis and reduced learning memory ability observed in these three diseases and also after radiation exposure.


Asunto(s)
Enfermedad de Alzheimer , Depresión , MicroARNs , Neurogénesis , Exposición a la Radiación/efectos adversos , Esquizofrenia , Enfermedad de Alzheimer/genética , Biomarcadores , Depresión/genética , Humanos , MicroARNs/genética , Radiación Ionizante , Esquizofrenia/genética
18.
Curr Med Chem ; 28(10): 1970-1986, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32520676

RESUMEN

Radiotherapy is a common treatment for brain and spinal cord tumors and also a risk factor for neuropathological changes in the brain leading to different neurological and neuropsychological disorders. Astroglial connexins are involved in brain inflammation, development of Alzheimer's Disease (AD), depressive, epilepsy, and amyotrophic lateral sclerosis, and are affected by radiation exposure. Therefore, it is speculated that radiation-induced changes of astroglial connexins may be related to the brain neuropathology and development of neurological and neuropsychological disorders. In this paper, we review the functional expression and regulation of astroglial connexins expressed between astrocytes and different types of brain cells (including oligodendrocytes, microglia, neurons and endothelial cells). The roles of these connexins in the development of AD, depressive, epilepsy, amyotrophic lateral sclerosis and brain inflammation have also been summarized. The radiation-induced astroglial connexins changes and development of different neurological and neuropsychological disorders are then discussed. Based on currently available data, we propose that radiation-induced astroglial connexins changes may be involved in the genesis of different neurological and neuropsychological disorders which depends on the age, brain regions, and radiation doses/dose rates. The abnormal astroglial connexins may be novel therapeutic targets for the prevention of radiation-induced cognitive impairment, neurological and neuropsychological disorders.


Asunto(s)
Astrocitos , Conexinas , Enfermedades del Sistema Nervioso , Exposición a la Radiación , Células Endoteliales , Humanos
19.
Aging (Albany NY) ; 13(12): 15815-15832, 2021 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-34162763

RESUMEN

Gamma H2A histone family member X (γH2AX) is a molecular marker of aging and disease. However, radiosensitivity of the different brain cells, including neurons, glial cells, cells in cerebrovascular system, epithelial cells in pia mater, ependymal cells lining the ventricles of the brain in immature animals at different postnatal days remains unknown. Whether radiation-induced γH2AX foci in immature brain persist in adult animals still needs to be investigated. Hence, using a mouse model, we showed an extensive postnatal age-dependent induction of γH2AX foci in different brain regions at 1 day after whole body gamma irradiation with 5Gy at postnatal day 3 (P3), P10 and P21. P3 mouse brain epithelial cells in pia mater, glial cells in white matter and cells in cerebrovascular system were more radiosensitive at one day after radiation exposure than those from P10 and P21 mice. Persistent DNA damage foci (PDDF) were consistently demonstrated in the brain at 120 days and 15 months after irradiation at P3, P10 and P21, and these mice had shortened lifespan compared to the age-matched control. Our results suggest that early life irradiation-induced PDDF at later stages of animal life may be related to the brain aging and shortened life expectancy of irradiated animals.


Asunto(s)
Giro Dentado/metabolismo , Giro Dentado/efectos de la radiación , Rayos gamma , Histonas/metabolismo , Animales , Animales Recién Nacidos , Ratones , Análisis de Supervivencia , Factores de Tiempo
20.
Cells ; 10(12)2021 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-34944078

RESUMEN

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer's disease and Parkinson's disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.


Asunto(s)
Encéfalo/patología , Senescencia Celular/efectos de la radiación , Radiación Ionizante , Animales , Autofagia/efectos de la radiación , Humanos , Mitocondrias/patología , Mitocondrias/efectos de la radiación , Estrés Oxidativo/efectos de la radiación
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