RESUMO
Underwater images have chromatic aberrations under different light sources and complex underwater scenes, which can lead to the wrong choice when using an underwater robot. To solve this problem, this paper proposes an underwater image illumination estimation model, which we call the modified salp swarm algorithm (SSA) extreme learning machine (MSSA-ELM). It uses the Harris hawks optimization algorithm to generate a high-quality SSA population, and uses a multiverse optimizer algorithm to improve the follower position that makes an individual salp carry out global and local searches with a different scope. Then, the improved SSA is used to iteratively optimize the input weights and hidden layer bias of ELM to form a stable MSSA-ELM illumination estimation model. The experimental results of our underwater image illumination estimations and predictions show that the average accuracy of the MSSA-ELM model is 0.9209. Compared to similar models, the MSSA-ELM model has the best accuracy for underwater image illumination estimation. The analysis results show that the MSSA-ELM model also has high stability and is significantly different from other models.
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Amyotrophic lateral sclerosis (ALS), a multicomplex neurodegenerative disease, has multiple underlying pathological factors and can induce other neuromuscular diseases, leading to muscle atrophy and respiratory failure. Currently, there is no effective drug for treating patients with ALS. Herbal medicine, used to treat various diseases, has multitarget effects and does not usually induce side effects. Each bioactive component in such herbal combinations can exert a mechanism of action to increase therapeutic efficacy. Herein, we investigated the efficacy of an herbal formula, comprising Achyranthes bidentata Blume, Eucommia ulmoides Oliver, and Paeonia lactiflora Pallas, in suppressing the pathological mechanism of ALS in male hSOD1G93A mice. Herbal formula extract (HFE) (1 mg/g) were orally administered once daily for six weeks, starting at eight weeks of age, in hSOD1G93A transgenic mice. To evaluate the effects of HFE, we performed footprint behavioral tests, western blotting, and immunohistochemistry to detect protein expression and quantitative PCR to detect mRNA levels in the muscles and spinal cord of hSOD1G93A mice. HFE-treated hSOD1G93A mice showed increased anti-inflammation, antioxidation, and regulation of autophagy in the muscles and spinal cord. Thus, HEF can be therapeutic candidates for inhibiting disease progression in patients with ALS. This study has some limitations. Although this experiment was performed only in male hSOD1G93A mice, studies that investigate the efficacy of HEF in various ALS models including female mice, such as mice modeling TAR DNA-binding protein 43 (TDP43) and ORF 72 on chromosome 9 (C9orf72) ALS, are required before it can be established that HEF are therapeutic candidates for patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Músculos/metabolismo , Doenças Neurodegenerativas/metabolismo , Medula Espinal/patologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genéticaRESUMO
Fear memory helps animals and humans avoid harm from certain stimuli and coordinate adaptive behavior. However, excessive consolidation of fear memory, caused by the dysfunction of cellular mechanisms and neural circuits in the brain, is responsible for post-traumatic stress disorder and anxiety-related disorders. Dysregulation of specific brain regions and neural circuits, particularly the hippocampus, amygdala, and medial prefrontal cortex, have been demonstrated in patients with these disorders. These regions are involved in learning, memory, consolidation, and extinction. These are also the brain regions where new neurons are generated and are crucial for memory formation and integration. Therefore, these three brain regions and neural circuits have contributed greatly to studies on neural plasticity and structural remodeling in patients with psychiatric disorders. In this review, we provide an understanding of fear memory and its underlying cellular mechanisms and describe how neural circuits are involved in fear memory. Additionally, we discuss therapeutic interventions for these disorders based on their proneurogenic efficacy and the neural circuits involved in fear memory.
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Condicionamento Clássico , Extinção Psicológica , Animais , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Humanos , Córtex Pré-Frontal/fisiologiaRESUMO
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA causes cognitive improvements in AD and vascular dementia. However, EA-induced changes in cognition and microglia-mediated amyloid ß (Aß) degradation have not been determined yet in AD animals. Therefore, this study investigated the EA-induced molecular mechanisms causing cognitive improvement and anti-inflammatory activity in five familial mutation (5XFAD) mice, an animal model of AD. METHODS: 5XFAD mice were bilaterally treated with EA at the Taegye (KI3) acupoints three times per week for 2 weeks. To evaluate the effects of EA treatment on cognitive functions, novel object recognition and Y-maze tests were performed with non-Tg, 5XFAD (Tg), and EA-treated 5XFAD (Tg + KI3) mice. To examine the molecular mechanisms underlying EA effects, western blots, immunohistochemistry, and micro-positron emission tomography scans were performed. Furthermore, we studied synapse ultrastructures with transmission electron microscopy and used electrophysiology to investigate EA effects on synaptic plasticity in 5XFAD mice. RESULTS: EA treatment significantly improved working memory and synaptic plasticity, alleviated neuroinflammation, and reduced ultrastructural degradation of synapses via upregulation of synaptophysin and postsynaptic density-95 protein in 5XFAD mice. Furthermore, microglia-mediated Aß deposition was reduced after EA treatment and coincided with a reduction in amyloid precursor protein. CONCLUSIONS: Our findings demonstrate that EA treatment ameliorates cognitive impairment via inhibition of synaptic degeneration and neuroinflammation in a mouse model of AD.
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Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/terapia , Modelos Animais de Doenças , Eletroacupuntura/métodos , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Camundongos , Camundongos TransgênicosRESUMO
Amyotrophic lateral sclerosis (ALS), a progressive disorder, causes motor neuron degeneration and neuromuscular synapse denervation. Because this is a complex disease, there are no effective drugs for the treatment of patients with ALS. For example, riluzole is used in many countries but has many side effects and only increases the lifespan of patients by approximately 2-3 months. Therefore, patients with ALS often turn to complementary and alternative medicine, such as acupuncture, homeopathy, and herbal medicine, with the hope and belief of recovery, despite the lack of definite evidence on the efficacy of these methods. Gamisoyo-San (GSS), a herbal medicine known to improve health, has been used for stress-related neuropsychological disorders, including anorexia, in Asian countries, such as China, Korea, and Japan. To evaluate the effects of GSS on the spinal cord, we investigated the expression of neuroinflammatory and metabolic proteins in symptomatic hSOD1G93A mice. We observed that GSS reduces the expression of glial markers, including those for microglia and astrocytes, and prevents neuronal loss. Moreover, we found that GSS inhibits the expression of proteins related to Toll-like receptor 4 signaling and oxidative stress, known to cause neuroinflammation. Notably, GSS also regulates metabolism in the spinal cord of transgenic mice. These results suggest that GSS could be used for improving the immune system and increasing the life quality of patients with ALS.
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Esclerose Lateral Amiotrófica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Preparações de Plantas/farmacologia , Medula Espinal/efeitos dos fármacos , Superóxido Dismutase-1/genética , Esclerose Lateral Amiotrófica/genética , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Heme Oxigenase-1/metabolismo , Sistema Imunitário , Inflamação/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Doenças do Sistema Nervoso/patologia , Neuroglia/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Qualidade de Vida , Transdução de Sinais , Medula Espinal/patologia , Receptor 4 Toll-Like/metabolismo , Transferrina/metabolismoRESUMO
Lilii Bulbus (Lilium lancifolium Thunberg) has a proneurogenic effect on the hippocampus. However, its effects on epilepsy and associated pathological features remain unknown. In this study, we investigated the antiseizure effects of a water extract of Lilii Bulbus (WELB) in mouse model of pentylenetetrazol (PTZ)-induced seizure. Mice were injected with PTZ once every 48â¯h until full kindling was achieved. WELB (100 and 500â¯mg/kg) was orally administered once daily before PTZ administration and during the kindling process. We found that WELB treatment protected against PTZ-induced low seizure thresholds and high seizure severity. Further, WELB-treated mice showed attenuated PTZ kindling-induced anxiety and memory impairment. Immunostaining and immunoblots showed that hyperactivation and ectopic migration of dentate granule cells (DGCs) were significantly reduced by WELB treatment in PTZ kindling-induced seizure mice. Staining for mossy fiber sprouting (MFS) using Timm staining and ZnT3 showed that WELB treatment significantly decreased PTZ kindling-induced MFS. Furthermore, the increased or decreased expression of proteins related to ectopic DGCs (Reelin and Dab-1), MFS (Netrin-1, Sema3A, and Sema3F), and their downstream effectors (ERK, AKT, and CREB) in the hippocampus of PTZ kindling mice was significantly restored by WELB treatment. Overall, our findings suggest that WELB is a potential antiseizure drug that acts by reducing ectopic DGCs and MFS and modulating epileptogenesis-related signaling in the hippocampus.
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Excitação Neurológica , Semaforinas , Animais , Camundongos , Netrina-1 , Pentilenotetrazol , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismoRESUMO
The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.
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Comportamento Animal , Metabolismo Energético , Neurônios , Transtornos de Estresse Pós-Traumáticos , Animais , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Camundongos , Gravidez , Masculino , Comportamento Animal/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Placenta/metabolismo , Modelos Animais de Doenças , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ansiedade/metabolismo , Ansiedade/tratamento farmacológico , Corticosterona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Citocinas/metabolismoRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS.Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity. METHODS: To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 µâ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting. RESULTS: In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively. CONCLUSIONS: Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.
Assuntos
Esclerose Lateral Amiotrófica/imunologia , Tronco Encefálico/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Esclerose Lateral Amiotrófica/patologia , Animais , Western Blotting , Tronco Encefálico/imunologia , Tronco Encefálico/patologia , Modelos Animais de Doenças , Alcaloides Diterpenos , Imunofluorescência , Humanos , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/patologia , Camundongos , Camundongos Transgênicos , Medula Espinal/imunologia , Medula Espinal/patologia , Superóxido Dismutase/genética , Superóxido Dismutase-1RESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model. METHODS: NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 µg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies. RESULTS: We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells. CONCLUSION: Our findings suggest that BV may rescue the impairment of the UPS in ALS models.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Venenos de Abelha/farmacologia , Abelhas , Neurônios Motores/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Superóxido Dismutase/metabolismo , Ubiquitina/metabolismo , Esclerose Lateral Amiotrófica/tratamento farmacológico , Animais , Apiterapia , Autofagia , Chaperona BiP do Retículo Endoplasmático , Humanos , Camundongos , Neurônios Motores/metabolismo , Mutação , Superóxido Dismutase/genética , Superóxido Dismutase-1 , TransfecçãoRESUMO
Panax ginseng C.A. Meyer has been used in traditional herb prescriptions for thousands of years. A heat-processing method has been used to increase the efficacy of ginseng, yielding what is known as red ginseng. In addition, recently, a slightly modified heat-processing method was applied to ginseng, to obtain a new type of processed ginseng with increased biological activity; this new form of ginseng is referred to as Sun ginseng (SG). The aim of this study was to investigate the effect of SG on memory enhancement and neurogenesis in the hippocampal dentate gyrus (DG) region. The subchronic administration of SG (for 14 days) significantly increased the latency time in the passive avoidance task relative to the administration of the vehicle control (P < 0.05). Western blotting revealed that the levels of phosphorylated extracellular signal-regulated kinase (pERK) and phosphorylated protein kinase B (pAkt) were significantly increased in hippocampal tissue after 14 days of SG administration (P < 0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining revealed that SG significantly enhanced the neuronal cell proliferation and the survival of immature neurons in the subgranular zone of the hippocampal DG region. These results suggest that SG has memory-enhancing activities and that these effects are mediated, in part, by the increase in the levels of pERK and pAkt and by the increases in cell proliferation and cell survival.
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Giro Denteado/efeitos dos fármacos , Memória/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Panax/química , Extratos Vegetais/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Giro Denteado/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by traumatic or frightening events, with intensified anxiety, fear memories, and cognitive impairment caused by a dysfunctional hippocampus. Owing to its complex phenotype, currently prescribed treatments for PTSD are limited. This study investigated the psychopharmacological effects of novel COMBINATION herbal medicines on the hippocampus of a PTSD murine model induced by combining single prolonged stress (SPS) and foot shock (FS). We designed a novel herbal formula extract (HFE) from Chaenomeles sinensis, Glycyrrhiza uralensis, and Atractylodes macrocephala. SPS+FS mice were administered HFE (500 and 1000 mg/kg) once daily for 14 days. The effects of HFE of HFE on the hippocampus were analyzed using behavioral tests, immunostaining, Golgi staining, and Western blotting. HFE alleviated anxiety-like behavior and fear response, improved short-term memory, and restored hippocampal dysfunction, including hippocampal neurogenesis alteration and aberrant migration and hyperactivation of dentate granule cells in SPS+FS mice. HFE increased phosphorylation of the Kv4.2 potassium channel, extracellular signal-regulated kinase, and cAMP response element-binding protein, which were reduced in the hippocampus of SPS+FS mice. Therefore, our study suggests HFE as a potential therapeutic drug for PTSD by improving behavioral impairment and hippocampal dysfunction and regulating Kv4.2 potassium channel-related pathways in the hippocampus.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Animais , Camundongos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Canais de Potássio Shal , Transtornos de Ansiedade , Modelos Animais , HipocampoRESUMO
Post-traumatic stress disorder (PTSD) is a mental disorder that develops after exposure to a traumatic event. Owing to the relatively low rates of response and remission with selective serotonin reuptake inhibitors as the primary treatment for PTSD, there is a recognized need for alternative strategies to effectively address the symptoms of PTSD. Dysregulation of glutamatergic neurotransmission plays a critical role in various disorders, including anxiety, depression, PTSD, and Alzheimer's disease. Therefore, the regulation of glutamate levels holds great promise as a therapeutic target for the treatment of mental disorders. Electroacupuncture (EA) has become increasingly popular as a complementary and alternative medicine approach. It maintains the homeostasis of central nervous system (CNS) function and alleviates symptoms associated with anxiety, depression, and insomnia. This study investigated the effects of EA at the GV29 (Yintang) acupoint three times per week for 2 weeks in an animal model of PTSD. PTSD was induced using single prolonged stress/shock (SPSS) in mice, that is, SPS with additional foot shock stimulation. EA treatment significantly reduced PTSD-like behavior and effectively regulated serum corticosterone and serotonin levels in the PTSD model. Additionally, EA treatment decreased glutamate levels and glutamate neurotransmission-related proteins (pNR1 and NR2B) in the hippocampus of a PTSD model. In addition, neuronal activity and the number of Golgi-impregnated dendritic spines were significantly lower in the EA treatment group than in the SPSS group. Notably, EA treatment effectively reduced glutamate-induced excitotoxicity (caspase-3, Bax, and pJNK). These findings suggest that EA treatment at the GV29 acupoint holds promise as a potential therapeutic approach for PTSD, possibly through the regulation of NR2B receptor-mediated glutamate neurotransmission to reduce PTSD-like behaviors.
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Eletroacupuntura , Transtornos de Estresse Pós-Traumáticos , Humanos , Camundongos , Animais , Transtornos de Estresse Pós-Traumáticos/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Modelos Animais de Doenças , Transmissão SinápticaRESUMO
Allergic rhinitis (AR), a chronic respiratory inflammatory disease, is among the most common chronic diseases reported worldwide. Mucus hypersecretion is a critical feature of AR pathogenesis. Although the Gleditsia sinensis extract has several beneficial effects on human health, its effects on allergic inflammation have not yet been investigated. In this study, we examined the effects of G. sinensis aqueous extract (GSAE) on nasal inflammation in an ovalbumin (OVA)-induced AR mouse model. GSAE was administered orally for 1 week and then the clinical nasal symptoms were evaluated. The levels of histamine, OVA-specific immunoglobulin (Ig) E, and interleukin (IL)-13 were measured in the serum using an enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were then counted in the nasal lavage fluid (NALF) and histopathology in the nasal epithelium was evaluated. STAT3/STAT6 phosphorylation was examined in primary human nasal epithelial cells (HNEpCs) using western blot analysis. Oral administration of GSAE to OVA-induced AR mice alleviated nasal clinical symptoms and reduced OVA-specific immunoglobulin E, interleukin (IL)-13, and histamine levels. The accumulation of eosinophils in nasal lavage fluid, nasal mucosa, mast cells, goblet cells, and mucin 5AC (MUC5AC) in the nasal epithelium was also inhibited by GSAE. Treatment with GSAE inhibited the production of MUC5AC in IL-4/IL-13-stimulated primary human nasal epithelial cells through the signal transducer and activator of transcription (STAT)3/STAT6 signaling pathway. These results indicated that GSAE reduces nasal inflammation suggesting that it is a potential treatment option for AR.
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Gleditsia , Rinite Alérgica , Humanos , Animais , Camundongos , Gleditsia/metabolismo , Histamina/metabolismo , Mucina-5AC/metabolismo , Citocinas/metabolismo , Rinite Alérgica/metabolismo , Mucosa Nasal/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Imunoglobulina E , Interleucina-13/metabolismo , Ovalbumina/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Fator de Transcrição STAT6/metabolismoRESUMO
Several molecules were recently found to be important for the memory retrieval process in the hippocampus; however, the mechanisms underlying the memory retrieval remain poorly understood. GSK-3ß has been implicated in the control of synaptic plasticity and memory formation. Here, we investigated the relationship between hippocampal GSK-3ß activity and memory retrieval using behavioral and Western blotting methods. We found that GSK-3ß was activated in the hippocampus after a retention session in the passive avoidance task. An intrahippocampal injection of the GSK-3ß inhibitor, SB 216763, before the retention session blocked memory retrieval (but not reconsolidation) without affecting locomotor activity. These results suggest that GSK-3ß activation would be essential for memory retrieval in the hippocampus.
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Quinase 3 da Glicogênio Sintase/fisiologia , Hipocampo/fisiologia , Retenção Psicológica/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Camundongos , Retenção Psicológica/efeitos dos fármacosRESUMO
The progressive neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is characterized by muscle weakness and atrophy owing to selective motoneuron degeneration. The anti-glutamatergic drug, riluzole (RZ), is the standard-of-care treatment for ALS. Bojungikgi-tang (BJIGT), a traditional herbal formula, improves motor function and prolongs the survival of mice with ALS. As ALS is a multicomplex disease, effective therapies must target multiple mechanisms. Here, we evaluated the efficacy of a BJIGT/RZ combination (5-week treatment) in 2-month-old hSOD1G93A mice with ALS. We performed quantitative polymerase chain reaction, Western blotting, immunohistochemistry, and enzyme activity assays. BJIGT/RZ significantly attenuated inflammation, autophagy, and metabolic and mitochondrial dysfunctions in the gastrocnemius (GC) compared with the control. It reduced the mRNA and protein levels of muscle denervation-related proteins and creatine kinase levels. The total creatine level was significantly higher in the BJIGT/RZ-treated GC. Moreover, after BJIGT/RZ treatment, the number of Nissl-stained motoneurons and choline acetyl transferase-positive neurons in the spinal cord significantly increased via the regulation of proinflammatory cytokines. Collectively, the BJIGT/RZ treatment was superior to single-drug treatments in alleviating multiple ALS-related pathological mechanisms in the ALS mouse model. Overall, BJIGT can serve as a dietary supplement and be combined with RZ to achieve superior therapeutic effects against ALS.
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Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic events and is characterized by overwhelming fear and anxiety. Disturbances in the hypothalamic-pituitary-adrenal (HPA) axis are involved in the pathogenesis of mood disorders, including anxiety, PTSD, and major depressive disorders. Studies have demonstrated the relationship between the HPA axis response and stress vulnerability, indicating that the HPA axis regulates the immune system, fear memory, and neurotransmission. The selective serotonin reuptake inhibitors (SSRIs), sertraline and paroxetine, are the only drugs that have been approved by the United States Food and Drug Administration for the treatment of PTSD. However, SSRIs require long treatment times and are associated with lower response and remission rates; therefore, additional pharmacological interventions are required. Complementary and alternative medicine therapies ameliorate HPA axis disturbances through regulation of gut dysbiosis, insomnia, chronic stress, and depression. We have described the cellular and molecular mechanisms through which the HPA axis is involved in PTSD pathogenesis and have evaluated the potential of herbal medicines for PTSD treatment. Herbal medicines could comprise a good therapeutic strategy for HPA axis regulation and can simultaneously improve PTSD-related symptoms. Finally, herbal medicines may lead to novel biologically driven approaches for the treatment and prevention of PTSD.
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Growth hormone (GH)/insulin-like growth factor-I deficiencies are known to cause alterations in brain development resulting in impairment of cognitive function. In order to investigate the behavioral phenotype of GH-deficient spontaneous dwarf rats (SDRs), we examined the behavior of the SDRs in the Morris water maze and Y-maze tasks. The SDRs showed severe deficits in spatial learning and memory compared to normal rats. The possibility that the cognitive impairment is associated with alteration of neurotransmitter systems was examined histologically following completion of the behavioral tests, using choline acetyltransferase (ChAT), vesicular glutamate transporter 1 (VGlut1) and glutamic acid decarboxylase (GAD6) immunohistochemistry as markers. In the SDRs the number of ChAT-stained basal forebrain cholinergic neurons was decreased. ChAT staining was also decreased in the hippocampus, one of the target areas of basal forebrain cholinergic neurons. Next, we examined the number of glutamatergic and GABAergic boutons in the hippocampal molecular layer and found a significant reduction in the density of VGlut1+ boutons and an increase in GAD6+ profiles, leading to a significantly reduced ratio in glutamatergic/GABAergic synapses. Finally, the number of newly generated cells in the subgranular zone of the hippocampus was significantly lower than in normal rats. Taken together, our data suggest that GH is an important regulator of hippocampus-dependent spatial learning and memory. The behavioral deficits in the SDRs may be explained by altered basal forebrain cholinergic innervation, imbalance in hippocampal glutamatergic/GABAergic synapses, and decreased neurogenesis in the hippocampus.
Assuntos
Nanismo Hipofisário/fisiopatologia , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/fisiopatologia , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Acetilcolina/fisiologia , Animais , Colina O-Acetiltransferase/metabolismo , Glutamato Descarboxilase/metabolismo , Glutamatos/fisiologia , Masculino , Memória/fisiologia , Neurônios/fisiologia , Ratos , Sinapses/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by motor neuron loss and muscle atrophy. There is no prominent treatment for ALS as the pathogenic process in the skeletal muscle and spinal cord is complex and multifactorial. Therefore, we investigated the effects of a herbal formula on the multi-target effects in the skeletal muscle and spinal cord in hSOD1G93A transgenic mice. We prepared a herbal extract (HE) from Glycyrrhiza uralensis, Atractylodes macrocephala Koidzumi, Panax ginseng, and Astragalus membranaceus. Control and HE-treated mice underwent rotarod and footprint tests. We also performed immunohistochemical and Western blotting analyses to assess expression of inflammation-related and oxidative stress-related proteins in the muscle and spinal cord tissues. We found that the HE increased motor activity and reduced motor neuron loss in hSOD1G93A mice. In addition, the HE significantly reduced the levels of inflammatory proteins and oxidative stress-related proteins in the skeletal muscles and spinal cord of hSOD1G93A mice. Furthermore, we demonstrated that the HE regulated autophagy function and augmented neuromuscular junction in the muscle of hSOD1G93A mice. Based on these results, we propose that the HE formula may be a potential therapeutic strategy for multi-target treatment in complex and multifactorial pathological diseases.
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BACKGROUND: Cognitive impairment is an age-dependent chronic disorder that exponentially worsens with age; however, its treatment is mostly symptomatic. Moxibustion is widely accepted in East Asia as a treatment for cognitive impairment. This systematic review aimed to verify the efficacy and underlying mechanism of moxibustion in treating cognitive impairment. METHODS: Sixteen trials involving 324 animals obtained from MEDLINE (PubMed), EMBASE, the Cochrane library, the Chinese National Knowledge Infrastructure, Wan-Fang, Cqvip, the Korean Studies Information Service System, and the Oriental Medicine Advanced Searching Integrated System met the inclusion criteria. We extracted the results of behavioral tests and immunohistochemical biomarkers from the included articles and evaluated the risk of bias and reporting quality. RESULTS: The moxibustion group showed significantly decreased escape latency, increased crossing times, and prolonged dwelling times in the Morris water maze test. There was a significantly enhanced latency period and reduced error time in the step-down test and nerve behavior score. The effects of moxibustion were found to be mediated by suppression of oxidative stress and apoptosis, modulation of inflammation and Aß genesis activation of vascular endothelial growth factor, and adjustment of metabolites in the tricarboxylic acid cycle and fatty acid metabolism. CONCLUSION: Our results demonstrated the therapeutic efficacy of moxibustion on cognitive impairment and suggested the putative mechanism. However, considering the small number of included studies, high bias risk, low reporting quality, and the limitations of animal experimentation, our results need to be confirmed by more detailed studies.
RESUMO
The complexity of pathological mechanisms in Alzheimer's disease (AD) poses significant challenges to the development of corresponding drugs. Symptom-specific pharmacological interventions and alternative treatments provide promising treatment possibilities. Therefore, we considered a combination of selegiline (SEL) and electroacupuncture (EA). We used an animal model with AD to investigate the effect of a combination of these treatments on cognitive function. 5XFAD mice received a week of SEL treatment and 2 weeks of EA. Novel object recognition and Y-maze tests were subsequently performed to assess their cognitive functions. To determine the molecular action of the combination treatment, Western blots, Aß1-42 enzyme-linked immunosorbent assays (ELISA), and micro-positron-emission tomography were also performed to assess pathological markers and processes. The results were assessed based on the difference between untreated transgenic, SEL-treated, and SEL- and EA-treated groups of mice. Mice in the combined treatment group demonstrated significantly better cognitive functions, and lesser neuroinflammation than the comparative groups. In addition, mice treated with a combination of SEL and EA did not demonstrate a direct modulation of insoluble Aß but demonstrated greater glucose metabolism. Our findings demonstrated that SEL combined with EA treatment was associated with better cognitive functioning due to inhibition of neuroinflammation and increased glucose metabolism relative to the comparative groups in a mouse model with AD.