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1.
Braz J Med Biol Res ; 54(3): e10428, 2021.
Article in English | MEDLINE | ID: mdl-33470393

ABSTRACT

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.


Subject(s)
Anxiety Disorders , Depression , Multiple Sclerosis , Anxiety Disorders/etiology , Biomarkers , Depression/etiology , Humans , Intermediate Filaments , Multiple Sclerosis/complications , Neurofilament Proteins
2.
Braz. j. med. biol. res ; 54(3): e10428, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153523

ABSTRACT

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.


Subject(s)
Humans , Anxiety Disorders/etiology , Depression/etiology , Multiple Sclerosis/complications , Intermediate Filaments , Biomarkers , Neurofilament Proteins
3.
Vet Microbiol ; 162(2-4): 866-872, 2013 Mar 23.
Article in English | MEDLINE | ID: mdl-23206410

ABSTRACT

Escherichia coli Vacuolating Factor (ECVF) is a heat-labile, vacuolating cytotoxin produced by avian pathogenic E. coli (APEC) isolated from avian cellulitis lesions. In this report, we intend to demonstrate that purified ECVF induces the inflammatory process of cellulitis. Our group is the first to demonstrate the effect of ECVF in a histological analysis by in situ inoculation of broiler chickens with purified ECVF. The animals were inoculated with the APEC AC53 and with purified ECVF subcutaneously on their ventral surface (in the sternum region). The histological analysis showed different grades of an acute inflammatory response in the epidermis, dermis and panniculus. An increase in mRNA expression of the proinflammatory cytokine TNF-α was also demonstrated in the inflamed tissue. When ECVF was systemically administered, increased levels of TNF-α and IL-10 were observed in the serum. These results suggest that ECVF plays a key role in the inflammatory process associated with cellulitis that is mainly mediated by TNF-α. In addition, this inflammation can be downregulated by the anti-inflammatory cytokine IL-10.


Subject(s)
Bacterial Toxins/biosynthesis , Bacterial Toxins/toxicity , Cellulitis/veterinary , Escherichia coli Infections/veterinary , Escherichia coli/metabolism , Poultry Diseases/chemically induced , Poultry Diseases/microbiology , Animals , Cellulitis/blood , Cellulitis/chemically induced , Cellulitis/microbiology , Chick Embryo , Chickens , Escherichia coli/genetics , Escherichia coli Infections/blood , Escherichia coli Infections/chemically induced , Escherichia coli Infections/microbiology , Interleukin-10/biosynthesis , Interleukin-10/blood , Interleukin-10/genetics , Male , Poultry Diseases/blood , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/genetics
5.
J Comp Neurol ; 518(7): 990-1007, 2010 Apr 01.
Article in English | MEDLINE | ID: mdl-20127802

ABSTRACT

Recent studies have shown that major histocompatibility complex class I (MHC I) expression directly influences the stability of nerve terminals. Also, the acute phase of experimental autoimmune encephalomyelitis (EAE) has shown a significant impact on inputs within the spinal cord. Therefore, the present work investigated the synaptic covering of motoneurons during the induction phase of disease and progressive remissions of EAE. EAE was induced in C57BL/6J mice, which were divided into four groups: normal, peak disease, first remission, and second remission. The animals were killed and their lumbar spinal cords processed for in situ hybridization (IH), immunohistochemistry, and transmission electron microscopy (TEM). The results indicated an increase in glial reaction during the peak disease. During this period, the TEM analysis showed a reduction in the synaptic covering of the motoneurons, corresponding to a reduction in synaptophysin immunolabeling and an increase in the MHC I expression. The IH analysis reinforced the immunolabeling results, revealing an increased expression of MHC I mRNA by motoneurons and nonneuronal cells during the peak disease and first remission. The results observed in both remission groups indicated a return of the terminals to make contact with the motoneuron surface. The ratio between excitatory and inhibitory inputs increased, indicating the potential for development of an excitotoxic process. In conclusion, the results presented here indicate that MHC I up-regulation during the course of EAE correlates with the periods of synaptic plasticity induced by the infiltration of autoreactive immune cells and that synaptic plasticity decreases after recurrent peaks of inflammation.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Histocompatibility Antigens Class I/metabolism , Motor Neurons/metabolism , Neuroglia/immunology , Animals , Disease Models, Animal , Disease Progression , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Glial Fibrillary Acidic Protein/metabolism , Histocompatibility Antigens Class I/genetics , Immunohistochemistry , In Situ Hybridization , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Motor Neurons/immunology , Motor Neurons/ultrastructure , Neuroglia/metabolism , Neuronal Plasticity , Presynaptic Terminals/immunology , Presynaptic Terminals/metabolism , RNA, Messenger , Recurrence , Spinal Cord/immunology , Spinal Cord/metabolism , Spinal Cord/ultrastructure , Synaptophysin/metabolism , Time Factors , Up-Regulation , beta 2-Microglobulin/metabolism
6.
Braz J Med Biol Res ; 42(2): 179-88, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19274346

ABSTRACT

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model--experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Neuronal Plasticity/drug effects , Peptides/therapeutic use , Spinal Cord/drug effects , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Astrocytes/ultrastructure , Encephalomyelitis, Autoimmune, Experimental/metabolism , Female , Glatiramer Acetate , Microscopy, Electron, Transmission , Motor Neurons/drug effects , Motor Neurons/physiology , Multiple Sclerosis/metabolism , Neuronal Plasticity/physiology , Rats , Rats, Inbred Lew , Spinal Cord/metabolism , Spinal Cord/ultrastructure , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Synaptophysin/analysis
7.
Braz. j. med. biol. res ; 42(2): 179-188, Feb. 2009. ilus, graf
Article in English | LILACS | ID: lil-506879

ABSTRACT

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.


Subject(s)
Animals , Female , Rats , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Neuronal Plasticity/drug effects , Peptides/therapeutic use , Spinal Cord/drug effects , Astrocytes/drug effects , Astrocytes/metabolism , Astrocytes/ultrastructure , Encephalomyelitis, Autoimmune, Experimental/metabolism , Microscopy, Electron, Transmission , Motor Neurons/drug effects , Motor Neurons/physiology , Multiple Sclerosis/metabolism , Neuronal Plasticity/physiology , Rats, Inbred Lew , Spinal Cord/metabolism , Spinal Cord/ultrastructure , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Synaptophysin/analysis
8.
Eur J Neurosci ; 24(11): 3053-62, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17156366

ABSTRACT

During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis-induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C-, F- and S-type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F- and S-type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F-terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro- and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.


Subject(s)
Motor Neurons/pathology , Multiple Sclerosis/physiopathology , Myasthenia Gravis, Autoimmune, Experimental/physiopathology , Nerve Degeneration/physiopathology , Neuronal Plasticity/physiology , Spinal Cord/physiopathology , Animals , Antigens, Differentiation/metabolism , Biomarkers/metabolism , Disease Models, Animal , Female , Glial Fibrillary Acidic Protein/metabolism , Gliosis/etiology , Gliosis/pathology , Gliosis/physiopathology , Microscopy, Immunoelectron , Motor Neurons/metabolism , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Myasthenia Gravis, Autoimmune, Experimental/metabolism , Myasthenia Gravis, Autoimmune, Experimental/pathology , Nerve Degeneration/etiology , Nerve Degeneration/pathology , Nerve Regeneration/physiology , Presynaptic Terminals/metabolism , Presynaptic Terminals/pathology , Rats , Rats, Inbred Lew , Recovery of Function/physiology , Spinal Cord/metabolism , Spinal Cord/pathology , Synaptophysin/metabolism
9.
Braz J Med Biol Res ; 36(3): 339-45, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12640498

ABSTRACT

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 +/- 8.9) was not different after tumor resection (43.6 +/- 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 +/- 5.8%, N = 20) or not (27.3 +/- 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 +/- 7.5%) or to healthy individuals (33.2 +/- 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF- ) since the patients with cancer had reduced production of TGF- Beta1 (269 +/- 239 pg/ml, N = 20) in comparison to the normal individuals (884 +/- 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF- 1 production by peripheral leukocytes.


Subject(s)
Lymphocyte Subsets/immunology , Stomach Neoplasms/immunology , Stomach Neoplasms/surgery , T-Lymphocytes, Helper-Inducer/immunology , Transforming Growth Factor beta/biosynthesis , Adult , Aged , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Lymphocyte Count , Male , Middle Aged
10.
Braz. j. med. biol. res ; 36(3): 339-345, Mar. 2003. tab, graf
Article in English | LILACS | ID: lil-329460

ABSTRACT

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 ± 8.9) was not different after tumor resection (43.6 ± 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 ± 5.8 percent, N = 20) or not (27.3 ± 7.3 percent, N = 20) compared to individuals with inflammatory disease (30.9 ± 7.5 percent) or to healthy individuals (33.2 ± 7.6 percent). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF-á) since the patients with cancer had reduced production of TGF-á1 (269 ± 239 pg/ml, N = 20) in comparison to the normal individuals (884 ± 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF-á1 production by peripheral leukocytes


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Lymphocyte Subsets , Stomach Neoplasms , T-Lymphocytes, Helper-Inducer , Transforming Growth Factor beta , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Immunity, Cellular , Lymphocyte Count
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