Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson / Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases

Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. [...] (AU)

Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases. (AU)

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. / Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Neuroprotective effect of acute and chronic administration of copper (II) sulfate against MPP+ neurotoxicity in mice.

Neurodegenerative effects of MPP+, the main metabolite of MPTP include dopamine (DA) depletion and enhanced lipid peroxidation (LPO) in mice striata, both associated to free radicals overproduction. Since copper is related to several antioxidant enzymes, we tested its neuroprotective effect against MPP+-induced neurotoxicity (20 microg/3 microl). CuSO4 pretreatment was administrated by either acute (2.5 mg/kg, i.p.) or chronic (350 or 700 mg/l doses through drinking water, for 30 days) schemes. Acute administration blocked MPP+-induced striatal LPO only when administered 16 or 24 hours before MPP+, and prevented the DA-depleting effect only at 24 hours. Chronic CuSO4 prevented the LPO increase, and blocked the DA depletion only at the higher dose used (700 mg/l). Neuroprotective effect of CuSO4 was dependent on the dose and the time of pretreatment, which suggest that this lag could be related with mechanisms of activation or synthesis of copper-dependent proteins responsible of cellular defense against MPP+.

Transplant of cultured neuron-like differentiated chromaffin cells in a Parkinson's disease patient. A preliminary report.

BACKGROUND: Treatment of Parkinson's Disease (PD) has been attempted by others by transplanting either the patient's own adrenal medullary tissue or fetal substantia nigra into caudate or putamen areas. However, the difficulties inherent in using the patient's own adrenal gland, or the difficulty in obtaining human fetal tissue, has generated the need to find alternative methods. METHODS: We report here of an alternative to both procedures by using as transplant material cultured human adrenal chromaffin cells differentiated into neuron-like cells by extremely low frequency magnetic fields (ELF MF). RESULTS: The results of this study show that human differentiated chromaffin cells can be grafted into the caudate nucleus of a PD patient, generating substantial clinical improvement, as measured by the Unified Rating Scale for PD, which correlated with glucose metabolism and D2 DA receptor increases as seen in a PET scan, while allowing a 70% decrease in L-Dopa medication. DISCUSSION: This is the first preliminary report showing that transplants of cultured differentiated neuron-like cells can be successfully used to treat a PD patient.

Ectopic bone formation by composites of BMP and metal implants in rats.

Disc-shaped implants of titanium alloy (Ti-6Al-4V) were treated on one side by corundum-blasting (CB) or by coating with hydroxyapatite (HA) or pure titanium (Ti) using plasma spraying. Half of the implants were additionally coated with purified swine BMP-3. The composites and the uncoated controls were implanted into abdominal wall-muscle pouches of rats. 25 days after implantation, ectopic bone formation could be observed macroscopically and histologically in a high frequency in all 3 groups of BMP-coated implants, whereas the controls were constantly inactive. The volumes of induced bone were similar for BMP-3-coated pure Ti and HA implants, while CB implants were significantly less active. Our findings indicate that the bone formation process is influenced by the chemical composition and by the structure of the implant surface.