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1.
Femina ; 49(8): 501-504, 20210831.
Article in Portuguese | LILACS | ID: biblio-1342421

ABSTRACT

A bexiga hiperativa caracteriza-se pela urgência miccional, geralmente acompa- nhada de noctúria e aumento da frequência urinária. Trata-se de afecção preva- lente, com enorme comprometimento da qualidade de vida, em todos os seus as- pectos. Diversos biomarcadores vêm sendo estudados para melhor caracterização dos diferentes fenótipos da afecção, entre eles as neurotrofinas urinárias, o ATP, a genômica e a microbiota urinária. Acredita-se que tal caracterização poderá ter implicações para prevenção, fisiopatologia e individualização do tratamento.(AU)


The overactive bladder is characterized by urinary urgency, usually accompanied by nocturia and increased urinary frequency. It is a prevalent condition, with enormous impairment of quality of life, in all its aspects. Several biomarkers have been studied to better characterize the different phenotypes of the condition, including urinary neurotrophins, ATP, genomics and urinary microbiota. It is believed that such charac- terization may have implications for prevention, pathophysiology and individualiza- tion of treatment.(AU)


Subject(s)
Humans , Male , Female , Urinary Bladder, Overactive , Urinary Incontinence, Urge , Biomarkers , Adenosine Triphosphate , Genomics , Microbiota , Nerve Growth Factors
2.
Chinese Journal of Lung Cancer ; (12): 829-837, 2021.
Article in Chinese | WPRIM | ID: wpr-922136

ABSTRACT

BACKGROUND@#The anti-tumor effect of pigment epithelium-derived factor (PEDF) has been widely confirmed. However, the anti-tumor effect of its peptides is rarely reported. This study aims to investigate the effects of PEDF and its peptides on the apoptosis and migration of non-small cell lung cancer (NSCLC).@*METHODS@#In this study, A549 cells and H1299 cells were selected as the research object, and the cells were divided into normal group, PEDF treatment group, 34 peptide treatment group, 44 peptide treatment group and 34+44 peptide treatment group by administering different drugs at the same concentration to the cells. The proliferation activity of cells in each group was detected by CCK-8 method; the migration ability of cells was detected by scratch test; the expression levels of apoptosis related proteins such as protein kinase 3 (RIP3) and cleaved-caspase-3 were detected by Western blot; the expression levels of epithelial mesenchymal transition (EMT) markers in each group, such as cadherin (E-cadherin) and α-smooth muscle actin (α-SMA) were detected by Western blot; the apoptosis rate of each group was detected by flow cytometry.@*RESULTS@#The results of CCK-8 showed that PEDF and its peptides could inhibit cell proliferation, and the inhibitory effect of 34+44 peptide was the strongest (P<0.05); Observation under the microscope found that PEDF and its peptides can inhibit the proliferation and mesenchymal transformation of A549 cells and H1299 cells, and the inhibitory effect of the 34+44 peptide group is the most obvious; Western blot indicated that compared with other groups, the expressions of cleaved-caspase-3 and RIP3 in 34+44 peptide group were significantly higher (P<0.05), and the expressions of EMT protein E-cadherin were higher, the expression of α-SMA decreased (P<0.05); The results of flow cytometry showed that the apoptosis rate of 34+44 peptide group was significantly higher than those of other groups (P<0.05); The scratch test showed that compared with all the other groups, the healing rate of 34+44 peptide group was the lowest (P<0.05).@*CONCLUSIONS@#34+44 combination peptide can better promote the apoptosis of NSCLC, inhibit the migration of NSCLC, and thereby inhibit the growth of NSCLC.


Subject(s)
Apoptosis , Cadherins/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Caspase 3 , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Eye Proteins , Humans , Lung Neoplasms/genetics , Nerve Growth Factors , Peptides/pharmacology , Serpins , Sincalide
3.
Article in English | WPRIM | ID: wpr-785341

ABSTRACT

PURPOSE: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps.METHODS: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting.RESULTS: The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA.CONCLUSIONS: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.


Subject(s)
Blotting, Western , Enzyme-Linked Immunosorbent Assay , Eosinophils , Fluorescent Antibody Technique , Humans , Immunoglobulin A , Immunoglobulin E , Immunoglobulin G , Immunoglobulins , Immunohistochemistry , Inflammation , Mucous Membrane , Nasal Polyps , Nerve Growth Factor , Nerve Growth Factors , Phosphotransferases , Plasma Cells , Plasma , Polyps , Real-Time Polymerase Chain Reaction , RNA, Messenger , Tropomyosin
4.
Mem. Inst. Oswaldo Cruz ; 115: e200075, 2020. graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135240

ABSTRACT

BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.


Subject(s)
Humans , Animals , Mice , Schwann Cells/metabolism , Sciatic Nerve/metabolism , Mycobacterium leprae , Nerve Growth Factors/metabolism , Mice, Nude
5.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(5): 419-427, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1039115

ABSTRACT

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.


Subject(s)
Animals , Male , Bipolar Disorder/immunology , Disease Models, Animal , Lisdexamfetamine Dimesylate , Lithium/pharmacology , Anti-Inflammatory Agents/pharmacology , Nerve Growth Factors/drug effects , Time Factors , Bipolar Disorder/physiopathology , Bipolar Disorder/chemically induced , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Brain-Derived Neurotrophic Factor/blood , Nitric Oxide Synthase Type II/blood , Locomotion/drug effects
6.
Arq. bras. oftalmol ; 82(4): 275-282, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019420

ABSTRACT

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.


RESUMO Objetivo: Comparar as concentrações intravítreas de mediadores celulares envolvidos na neurodegeneração, inflamação e angiogênese em pacientes com retinopatia diabética proliferativa e outras doenças vítreo-retinianas. Métodos: Um ensaio imunomagnético foi utilizado para medir os níveis vítreos do fator derivado do epitélio pigmentar, amilóide P sérico, proteína-C-reativa, complemento C4, e alfa-1-antitripsina, fator de crescimento do endotélio vascular, fator de crescimento derivado das plaquetas AA, fator de crescimento derivado das plaquetas BB, interleucina-6, interleucina-8, interleucina-10, fator de necrose tumoral alfa e beta em pacientes submetidos à vitrectomia 23-gauge para retinopatia diabética proliferativa ou outros diagnósticos (grupo controle). Resultados: Foram avaliados 55 pacientes, dos quais 24 tinham retinopatia diabética proliferativa e 31 tinham outros diagnósticos, incluindo hemorragia vítrea, descolamento de retina, buraco macular e membrana epirretiniana. Pacientes com retinopatia diabética proliferativa demonstraram níveis aumentados de amilóide P sérico (85,49 vs 31,38 ng/mL), proteína-C-reativa (59,89 vs 41,75 ng/mL), fator de crescimento do endotélio vascular (2.330,11 vs 554,25 pg/mL, p<0.001), fator de crescimento derivado das plaquetas-A: (127,32 vs 39,11 pg/mL), fator de crescimento derivado das plaquetas-B (29,37 vs 7,12 pg/mL), interleucina-6 (69,37 vs 33,58 pg/mL), interleucina-8 (175,25 vs 59,71 pg/mL) e interleucina-10 (3,70 vs 1,88 pg/mL), todos com p<0,004 quando comparados ao grupo controle. Níveis de fator derivado do epitélio pigmentar (30,06 vs 27,48 ng/mL; p=0,295), complemento C4 (570,78 vs 366,24 ng/mL; p=0,069), alfa-1 antitripsina (359,27 vs 522,44 ng/mL; p=0,264) não foram significativamente diferente entre os grupos. Níveis intravítreos de fator de necrose tumoral alfa e fator de necrose tumoral beta foram indetectáveis. O amilóide P sérico, a proteína C-reativa, o fator de crescimento derivado das plaquetas A e B, a interleucina-6 e a interleucina-8 correlacionaram-se positivamente com o fator de crescimento do endotélio vascular. Conclusões: Os medidores celulares envolvidos na neurodegeneração e inflamação demonstraram níveis aumentados no humor vítreo de pacientes com retinopatia diabética proliferativa e podem ser parte da patogênese da retinopatia diabética.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Retinal Degeneration/pathology , Vitreous Body/pathology , Inflammation Mediators/analysis , Diabetic Retinopathy/pathology , Reference Values , Vitrectomy , C-Reactive Protein/analysis , Platelet-Derived Growth Factor/analysis , Serum Amyloid P-Component/analysis , Serpins/analysis , Cross-Sectional Studies , Interleukins/analysis , Statistics, Nonparametric , Vascular Endothelial Growth Factor A/analysis , Diabetic Retinopathy/surgery , Eye Proteins/analysis , Nerve Growth Factors/analysis
7.
Rev. Col. Bras. Cir ; 46(2): e2094, 2019. tab, graf
Article in Portuguese | LILACS | ID: biblio-1003087

ABSTRACT

RESUMO Objetivo: determinar a expressão de neurotrofinas e seus receptores tirosina quinases em pacientes com osteossarcoma (OS) e sua correlação com desfechos clínicos. Métodos: biópsias de tumores primários de pacientes com OS tratados em uma única instituição, consecutivamente, entre 2002 e 2015, foram analisados através de imuno-histoquímica para expressão de receptores de tirosina quinase A e B (TrKA e TrKB), fator de crescimento neural (NGF) e fator neurotrófico derivado do cérebro (BDNF). De forma independente, dois patologistas classificaram os marcadores de imuno-histoquímica como negativos (negativos e focais fracos) ou positivos (moderado focal/difuso ou forte focal/difuso). Resultados: foram analisados dados de 19 pacientes (10 do sexo feminino e 9 do masculino) com mediana de idade de 12 anos (5 a 17,3 anos). Dos tumores, 83,3% estavam localizados em membros inferiores e 63,2% dos pacientes eram metastáticos ao diagnóstico. A sobrevida global em cinco anos foi de 55,3%. BDNF foi positivo em 16 pacientes (84%) e NGF em 14 pacientes (73%). TrKA e TrKB apresentaram coloração positiva em quatro (21,1%) e oito (42,1%) pacientes, respectivamente. A análise de sobrevida não demonstrou diferença significativa entre receptores TrK e neurotrofinas. Conclusão: amostras de OS primário expressam neurotrofinas e receptores TrK através de imuno-histoquímica. Estudos futuros podem auxiliar na identificação do papel das mesmas na patogênese do OS e determinar se há possível correlação prognóstica.


ABSTRACT Objective: to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. Methods: we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). Results: we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. Conclusion: primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Bone Neoplasms/pathology , Osteosarcoma/pathology , Brain-Derived Neurotrophic Factor/analysis , Receptor, trkA/analysis , Receptor, trkB/analysis , Nerve Growth Factors/analysis , Reference Values , Bone Neoplasms/mortality , Immunohistochemistry , Biomarkers, Tumor , Osteosarcoma/mortality , Risk Factors , Statistics, Nonparametric , Kaplan-Meier Estimate
8.
Acta cir. bras ; 34(12): e201901205, 2019. graf
Article in English | LILACS | ID: biblio-1054687

ABSTRACT

Abstract Purpose To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia. Methods Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined. Results Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1β levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). Conclusion HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.


Subject(s)
Humans , Animals , Male , Sesquiterpenes/pharmacology , Neuroprotective Agents/pharmacology , Anesthetics, Inhalation/adverse effects , Alkaloids/pharmacology , Hippocampus/drug effects , Nerve Growth Factors/drug effects , Enzyme-Linked Immunosorbent Assay , Random Allocation , Reproducibility of Results , Interleukin-6/analysis , Rats, Sprague-Dawley , Maze Learning , Interleukin-1beta/analysis , Hippocampus/metabolism , Isoflurane/adverse effects , Anesthesia/adverse effects , Nerve Growth Factors/analysis
9.
Article in Korean | WPRIM | ID: wpr-766566

ABSTRACT

Suicide is a complex phenomenon resulting from interactions between individual vulnerabilities and socio-environmental factors. The current review primarily focuses on research into the serotonin system, hypothalamic-pituitary-adrenal axis, neurotrophic factors, lipid metabolism, and functional neuroimaging studies. It has been found that dysfunctions in the serotonin system, hypothalamic-pituitary-adrenal axis abnormalities, and low brain-derived neurotrophic factor and cholesterol levels may be linked to suicide. Additionally, recent neuroimaging studies have suggested that structural and functional abnormalities in brain areas related to cognitive and emotional regulation may be associated with suicide. More research incorporating advanced methodological approaches may shed further light on the neurobiological basis of suicide.


Subject(s)
Brain , Brain-Derived Neurotrophic Factor , Cholesterol , Functional Neuroimaging , Lipid Metabolism , Nerve Growth Factors , Neurobiology , Neuroimaging , Pituitary-Adrenal System , Serotonin , Suicide
10.
The Korean Journal of Pain ; : 245-255, 2019.
Article in English | WPRIM | ID: wpr-761715

ABSTRACT

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.


Subject(s)
Adult , Adult Stem Cells , Aging , Cell Differentiation , Embryonic Stem Cells , Humans , Induced Pluripotent Stem Cells , Musculoskeletal Pain , Nerve Growth Factors , Neuralgia , Osteoarthritis , Stem Cell Transplantation , Stem Cells
11.
Article in English | WPRIM | ID: wpr-741923

ABSTRACT

To conceptualize a novel bio-psychosocial-behavioral treatment model of panic disorder (PD), it is necessary to completely integrate behavioral, psychophysiological, neurobiological, and genetic data. Molecular genetic research on PD is specifically focused on neurotransmitters, including serotonin, neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological interventions for PD are currently available, the need for more effective, faster-acting, and more tolerable pharmacological interventions is unmet. Thus, glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin-releasing factor 1 receptor antagonists, and other novel mechanism-based anti-panic therapeutics have been proposed. Research on the neural correlates of PD is focused on the dysfunctional “cross-talk” between emotional drive (limbic structure) and cognitive inhibition (prefrontal cortex) and the fear circuit, which includes the amygdala-hippocampus-prefrontal axis. The neural perspective regarding PD supports the idea that cognitive-behavioral therapy normalizes alterations in top-down cognitive processing, including increased threat expectancy and attention to threat. Consistent with the concept of “personalized medicine,” it is speculated that Research Domain Criteria can enlighten further treatments targeting dysfunctions underlying PD more precisely and provide us with better definitions of moderators used to identify subgroups according to different responses to treatment. Structuring of the “negative valence systems” domain, which includes fear/anxiety, is required to define PD. Therefore, targeting glutamate- and orexin-related molecular mechanisms associated with the fear circuit, which includes the amygdala-hippocampus-prefrontal cortex axis, is required to define a novel bio-psychosocial-behavioral treatment model of PD.


Subject(s)
Glucocorticoids , Molecular Biology , Nerve Growth Factors , Neuropeptides , Neurotransmitter Agents , Orexin Receptor Antagonists , Panic Disorder , Panic , Serotonin
12.
Rev. bras. psiquiatr ; 40(4): 367-375, Oct.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-959251

ABSTRACT

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.


Subject(s)
Animals , Male , Female , Plant Extracts/pharmacology , Cognition/drug effects , Hypericum , Frontal Lobe/metabolism , Hippocampus/metabolism , Nerve Growth Factors/analysis , Plant Extracts/administration & dosage , Random Allocation , Sex Factors , Treatment Outcome , Rats, Wistar , Models, Animal , Pattern Recognition, Physiological/drug effects , Dose-Response Relationship, Drug , Frontal Lobe/drug effects , Hippocampus/drug effects , Locomotion/drug effects , Memory/drug effects , Nerve Growth Factors/drug effects
13.
Rev. bras. psiquiatr ; 40(4): 361-366, Oct.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-959258

ABSTRACT

Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Cognitive Behavioral Therapy/methods , Brain-Derived Neurotrophic Factor/blood , Nerve Growth Factor/blood , Depressive Disorder, Major/blood , Glial Cell Line-Derived Neurotrophic Factor/blood , Psychiatric Status Rating Scales , Socioeconomic Factors , Severity of Illness Index , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Non-Randomized Controlled Trials as Topic , Nerve Growth Factors/blood
14.
Arq. neuropsiquiatr ; 76(5): 310-315, May 2018. tab, graf
Article in English | LILACS | ID: biblio-950539

ABSTRACT

ABSTRACT There is great evidence linking neurotrophic factor (NF) dysfunction with Parkinson's disease (PD) pathophysiology. This study was conducted to evaluate plasma levels of NFs and their possible associations with clinical symptoms in PD. For this purpose, 40 PD patients and 25 controls were subjected to a clinical evaluation and peripheral blood draw. Plasma levels of brain-derived neurotrophic factor (BDNF), pro-BDNF, neurotrophin 3, neurotrophin 4, nerve growth, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were measured by enzyme-linked immunosorbent assay. There was no significant difference between PD patients and controls regarding the plasma levels of the evaluated NFs. In addition, NF levels were not associated with disease duration, degree of motor or functional impairment, cognitive performance or severity of depressive symptoms. In conclusion, although NFs may play relevant roles in the pathophysiology of PD, the circulating levels of these molecules are not necessarily changed in patients with PD.


RESUMO Há evidências de que alteracões nas ações exercidas por fatores neurotróficos (FNs) estejam associadas à fisiopatologia da doença de Parkinson (DP). O presente estudo foi conduzido para avaliar os níveis plasmáticos de FNs e suas possíveis associações com sintomas clínicos na DP. Para este fim, 40 pacientes com DP e 25 controles foram submetidos à avaliação clínica e coleta de sangue periférico. Os níveis plasmáticos do fator neurotrófico derivado do cérebro (BDNF), pro-BDNF, neurotrofina 3, neurotrofina 4, fator de crescimento do nervo, fator neurotrófico derivado da glia e fator neurotrófico ciliar foram avaliados por ensaio de imunoadsorção enzimática. Não houve diferença significativa entre pacientes com DP e controles quanto aos níveis plasmáticos dos FNs avaliados. Além disso, não encontramos associação entre os níveis dos FNs e duração da doença, grau de comprometimento motor ou funcional, desempenho cognitivo e gravidade dos sintomas depressivos. Em conclusão, embora os FNs possam desempenhar papéis relevantes na fisiopatologia da DP, os níveis circulantes dessas moléculas não estão necessariamente alterados em pacientes com DP.


Subject(s)
Humans , Male , Female , Aged , Parkinson Disease/blood , Nerve Growth Factors/blood , Enzyme-Linked Immunosorbent Assay , Biomarkers/blood , Case-Control Studies , Cohort Studies
15.
Acta cir. bras ; 33(4): 341-353, Apr. 2018. graf
Article in English | LILACS | ID: biblio-886284

ABSTRACT

Abstract Purpose: To investigate the effect of hyperbaric oxygen therapy (HBOT) on traumatic brain injury (TBI) outcome. Methods: The modified Marmarou's weight drop device was used to generate non-lethal moderate TBI rat model, and further developed in vitro astrocytes culturing system. Then, we analyzed the expression changes of interested genes and protein by quantitative PCR and western blot. Results: Multiple HBO treatments significantly reduced the expression of apoptosis promoting genes, such as c-fos, c-jun, Bax and weakened the activation of Caspase-3 in model rats. On the contrary, HBOT alleviated the decrease of anti-apoptosis gene Bcl-2 and promoted the expression of neurotrophic factors (NTFs), such as NGF, BDNF, GDNF and NT-3 in vivo. As a consequent, the neuropathogenesis was remarkably relied with HBOT. Astrocytes from TBI brain or those cultured with 21% O2 density expressed higher NTFs than that of corresponding controls, from sham brain and cultured with 7% O2, respectively. The NTFs expression was the highest in astrocytes form TBI brain and cultured with 21% O2, suggesting a synergistic effect existed between TBI and the following HBO treatment in astrocytes. Conclusion: Our findings provided evidence for the clinical usage of HBO treating brain damages.


Subject(s)
Animals , Male , Brain Injuries, Traumatic/therapy , Hyperbaric Oxygenation/methods , Time Factors , Blotting, Western , Astrocytes/physiology , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Apoptosis/physiology , Disease Models, Animal , Caspase 3/physiology , Real-Time Polymerase Chain Reaction , Brain Injuries, Traumatic/pathology , Nerve Growth Factors/analysis
16.
Experimental Neurobiology ; : 189-199, 2018.
Article in English | WPRIM | ID: wpr-714909

ABSTRACT

Depression causes mental and physical changes which affect quality of life. It is estimated to become the second most prevalent disease, but despite its commonness, the pathophysiology of depression remains unclear and medicine is not sufficiently protective. p-Coumaric acid (p-CA) is a dietary phenolic acid which has been proven to have antifungal, anti-HIV, anti-melanogenic, antioxidant and anti-inflammatory effects. Considering these effects, we investigated whether p-CA can prevent depressive symptoms by reducing inflammatory cytokines in animals injected with lipopolysaccharide (LPS). Changes in despair-related behaviors, inflammatory cytokines, neurotrophic factors and synaptic activity were measured. In these animals, p-CA improved despair-related behavioral symptoms induced by LPS in the forced swim test (FST), tail suspension test (TST) and sucrose splash test (SST). p-CA also prevented the increase of inflammatory cytokines in the hippocampus such as cycloxigenase-2 and tumor necrosis factor-α due to LPS. Similarly, it prevented the reduction of brain-derived neurotrophic factor (BDNF) by LPS. Electrophysiologically, p-CA blocked the reduction of long-term depression in LPS-treated organotypic tissue slices. In conclusion, p-CA prevented LPS-induced depressive symptoms in animals, as determined by behavioral, biochemical and electrophysiological measures. These findings suggest the potential use of p-CA as a preventive and therapeutic medicine for depression.


Subject(s)
Animals , Behavioral Symptoms , Brain-Derived Neurotrophic Factor , Cytokines , Depression , Hindlimb Suspension , Hippocampus , Necrosis , Nerve Growth Factors , Phenol , Quality of Life , Rats , Sucrose
17.
Article in English | WPRIM | ID: wpr-758833

ABSTRACT

Previous studies have shown that the sciatic nerve has neurotrophic activity, and nerve regeneration, differentiation, and axon outgrowth can be modulated by different sciatic nerve preparations. However, numerous animals may have to be sacrificed to obtain enough sciatic nerves to make a sciatic nerve preparation. Some studies have demonstrated that the role of sciatic nerve preparations in neural differentiation depends on the neurotrophins that Schwann cells secrete, and these factors are highly conserved among different species. To reduce the use of experimental animals, in this study, we made a leachate by using the sciatic nerve of cattle and explored its effect on neuronal differentiation of rat PC12 cells (a useful model for studying neuronal differentiation). Results showed the neurite outgrowth of PC12 cells treated with the cattle sciatic nerve leachate for 3, 6, and 9 days was significantly improved, and the expressions of β3-tubulin and microtubule-associated protein 2 (two neuron-specific proteins) were increased. Moreover, the ERK1/2 signaling pathway was activated after PC12 cells were incubated with cattle sciatic nerve leachate for 9 days. Thus, a sciatic nerve leachate obtained from cattle can effectively induce neuronal differentiation of rat PC12 cells via ERK1/2 signaling pathway.


Subject(s)
Animals , Axons , Cattle , Microtubule-Associated Proteins , Nerve Growth Factors , Nerve Regeneration , Neurites , Neurons , PC12 Cells , Rats , Schwann Cells , Sciatic Nerve
18.
Article in Korean | WPRIM | ID: wpr-714573

ABSTRACT

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.


Subject(s)
Antidepressive Agents , Depression , Glutamic Acid , Humans , Interneurons , Ketamine , N-Methylaspartate , Nerve Growth Factors
19.
Article in English | WPRIM | ID: wpr-739525

ABSTRACT

Cognitive impairment is age-related and manageable only with early diagnosis and prevention. Moxibustion is widely accepted in East Asia as useful for preventing cognitive impairment. This systematic review of animal studies was conducted to verify the efficacy of moxibustion in preventing cognitive impairment and to elucidate the underlying mechanism. Randomized controlled animal trials that established the efficacy of moxibustion in preventing cognitive impairment were included in the analysis. Results of behavioral tests and the signaling pathways elucidated were extracted and a meta-analysis was conducted with the behavioral test results. The risk of bias was evaluated using 9 items, and reporting quality was evaluated using the ARRIVE (Animal Research: Reporting In Vivo Experiments) Guidelines Checklist. Ten trials involving 410 animals met the inclusion criteria. All studies reported the benefit of moxibustion in preventing cognitive deficits caused by Alzheimer's disease (AD). Among five studies using the Morris water maze test, a significant effect of moxibustion in decreasing the escape time was reported in three studies, increasing the crossing times in four studies, and prolonging the dwelling time in two studies. The effects of moxibustion were demonstrated to be mediated by an increase in the activity of neurotrophins and heat shock protein, modulation of the cell cycle, and suppression of apoptosis and inflammation. However, considering the small number of included studies, the lack of studies investigating entire signaling pathways, and a high risk of bias and low reporting quality, our results need to be confirmed through more detailed studies.


Subject(s)
Alzheimer Disease , Animal Experimentation , Animals , Apoptosis , Behavior Rating Scale , Bias , Cell Cycle , Checklist , Cognition Disorders , Early Diagnosis , Far East , Heat-Shock Proteins , Inflammation , Moxibustion , Nerve Growth Factors , United Nations , Water
20.
Article in English | WPRIM | ID: wpr-740031

ABSTRACT

PURPOSE: To evaluate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptor, GDNF family receptor alpha subunit 1 (GFRα-1) in the pelvic (middle third) vagina and, particularly, in the paravaginal ganglia of nulliparous and primiparous rabbits. METHODS: Chinchilla-breed female rabbits were used. Primiparas were killed on postpartum day 3 and nulliparas upon reaching a similar age. The vaginal tracts were processed for histological analyses or frozen for Western blot assays. We measured the ganglionic area, the Abercrombie-corrected number of paravaginal neurons, the cross-sectional area of the neuronal somata, and the number of satellite glial cells (SGCs) per neuron. The relative expression of both GDNF and GFRα-1 were assessed by Western blotting, and the immunostaining was semiquantitated. Unpaired two-tailed Student t -test or Wilcoxon test was used to identify statistically significant differences (P≤0.05) between the groups. RESULTS: Our findings demonstrated that the ganglionic area, neuronal soma size, Abercrombie-corrected number of neurons, and number of SGCs per neuron were similar in nulliparas and primiparas. The relative expression of both GDNF and GFRα-1 was similar. Immunostaining for both GDNF and GFRα-1 was observed in several vaginal layers, and no differences were detected regarding GDNF and GFRα-1 immunostaining between the 2 groups. In the paravaginal ganglia, the expression of GDNF was increased in neurons, while that of GFRα-1 was augmented in the SGCs of primiparous rabbits. CONCLUSIONS: The present findings suggest an ongoing regenerative process related to the recovery of neuronal soma size in the paravaginal ganglia, in which GDNF and GFRα-1 could be involved in cross-talk between neurons and SGCs.


Subject(s)
Blotting, Western , Carisoprodol , Female , Ganglia , Ganglion Cysts , Glial Cell Line-Derived Neurotrophic Factor , Humans , Nerve Growth Factors , Neuroglia , Neuronal Plasticity , Neurons , Postpartum Period , Rabbits , Reproduction , Vagina
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