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What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

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World Journal of Biological Chemistry 2014年第2期5卷 130-140页

作者： Maria da Graa Naffah-Mazzacoratti Telma Luciana Furtado Gouveia Priscila Santos Rodrigues Simōes Sandra Regina Perosa department de Bioquímica and departamento de neurologia/Neurocirurgia Universidade Federal de S?o Paulo (UNIFESP) S?o Paulo SP 4039032 Brazil

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

关键词： Kallikrein-kinin system Renin-angiotensin system Neurological disorders Alzheimer’s disease Epilepsy Parkinson’s disease

Changes in aminoacidergic and monoaminergic neurotransmission in the hippocampus and amygdala of rats after ayahuasca ingestion

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World Journal of Biological Chemistry 2013年第4期4卷 141-147页

作者： Eduardo Ferreira de Castro-Neto Rafael Henrique da Cunha Dartiu Xavier da Silveira Mauricio Yonamine Telma Luciana Furtado Gouveia Esper Abr o Cavalheiro Débora Amado Maria da Gra a Naffah-Mazzacoratti departamento neurologia/Neurocirurgia Universidade Federal de S o Paulo departamento de Psiquiatria Universidade Federal de S o Paulo Faculdade de Ciências Farmacêuticas Universidade de S o Paulo departamento de Bioquímica Universidade Federal de S o Paulo

AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P drenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P drenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P drenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amin

关键词： Ayahuasca Amino Acids Monoamines Hippocampus Amygdala

IL-1β, TNF-α and Sambucus nigra Reactive Serum Proteins as Biomarkers of Mild Cognitive Impairment and Alzheimer Disease Progression

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Advances in Alzheimer's Disease 2015年第4期4卷 99-109页

作者： Luis Manuel Castillo Enrique Moreno Yaneth Rodriguez-Agudelo MireyaChavez-Oliveros Zoila Trujillo Blanca Espinosa Emma Rodriguez-Maldonado Luis Felipe Montano Jorge Guevara departamento de Bioquimica Facultad de MedicinaUniversidad Nacional Autonoma de MexicoMexico CityMexico departamento de Neuropsicologia Instituto Nacional de Neurologia y NeurocirugiaMexico CityMexico Geriatra Instituto Nacional de neurologia y Neurocirugia Mexico CityMexico Laboratorio de Bioquimica Instituto Nacional de Enfermedades RespiratoriasMexico CityMexico departamento de Fisiología Instituto Nacional de CardiologiaMexico CityMexico departamento de Biologia Celular y Tisular Facultad de MedicinaUniversidad Nacional Autonoma de MexicoMexico CityMexico

Amyloid-β (Aβ) can induce a chronic inflammatory immune response that is associated, amongst many others, to abnormal glycosylation, inducible nitric oxide synthase (iNOS) and nitric oxide (NO). The relation between development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease progression and these serum markers has not been evaluated. Serum levels of iNOs, NO, TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 are determined with commercially available kits. Sialylation of albumin-free serum patterns is determined by Western blot analysis with Sambucus nigra (specific for sialic acid attached to terminal galactose in α2,6 linkage) lectin. Apolipoprotein E (ApoE) haplotype is determined by Western blot using specific anti-ApoE 2, 3 or 4 antibodies. A mini-mental state examination (MMSE) test is also performed in the 10 MCI patients, 19 Alzheimer’s disease (AD) patients and 46 healthy age-matched controls evaluated. The results show an increase of iNOS in MCI and AD but significantly higher NO concentrations are only found in MCI patients. TNF-α and IL-1β concentrations are the only significantly increased cytokines in MCI patients;no differences between control and MCI or AD patients are found in regard to the other cytokines. An abnormal MMSE test result only correlates with a decrease in serum NO concentration in MCI patients. The terminal sialic acid linkage pattern of serum proteins also shows highly significant differences between MCI and AD patient. ApoE3/4 or 4/4 haplotypes are characteristic of MCI and AD patients. Our results imply that increased serum TNF-α, IL-1β, iNOS, NO and alterations of serum proteins glycosylation patterns in adult individuals with an abnormal MMSE test may serve as an early biomarker of MCI and AD development.

关键词： Alzheimer Disease Mild Cognitive Impairment Nitric Oxide Inflammatory Cytokines Glycosylation Apolipoprotein E4

Correspondence amongst the PENO Test Battery Cognitive Results and Hippocampal Lesions in Alzheimer’s Disease

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Advances in Aging Research 2014年第3期3卷 239-251页

作者： Rojas Karla Diaz Alfonso Espinosa Blanca Montano Luis Felipe Dilhuydy Hugo Geraux Francine Joanette Yves Robitaille Yves Guevara Jorge Laboratorio Experimental de Enfermedades Neurodegenerativas Instituto Nacional de Neurologia y Neurocirugia“M.V.S.”Mexico DFMexico departamento de Farmacia Facultad de Ciencias QuimicasBUAPPueblaMexico departamento Bioquimica INERMexico DFMexico departamento de Biologia Celular y Tisular Facultad de MedicinaUNAMMexico DFMexico Centre de Recherche Institut Universitaire de Geriatrie de MontrealMontrealCanada departament de Pathologie Hopital Ste-JustineMontrealCanada departamento de Bioquimica Facultad de MedicinaUNAMMexico DFMexico

Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called “Meganeurite clusters” have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d’evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer’s patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as “plasticity” markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.

关键词： Cognitive decline Neuropsychological Evaluation Synapsis Plasticity Alzheimer’s Disease

Epidemiology of attention deficit disorder in Brazil: Implications for the Brazilian legal system

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Open Journal of Epidemiology 2013年第4期3卷 232-236页

作者： Sergio L.Schmidt Eunice Do Nascimento Simoes Guilherme J.Schmidt Marcela J.Schmidt Ana Lucia Novais Carvalho Laboratório de Neurofisiologia e Avaliacao Neurocomportamental Centro Biomédico State University of Rio de Janeiro Rio De Janeiro Brazil Instituto de neurologia deolindo Couto Federal University of Rio de Janeiro Rio de Janeiro Brazil Instituto de Ciências da Sociedade e desenvolvimento Regional Departamento de Fundamentos de Ciências da Sociedade Federal University Fluminense Niterói Brazil

In spite of the fact that the legal system adopted in Brazil is codified on the Roman tradition, there is no specific protection in law for people suffering from Attention deficit Disorder (ADD). In contrast, the law of the United States is largely derived from the common law system and there are two federal laws that guarantee a free appropriate public education and provide services to eligible students with disabilities. They are: Section 504 and Individuals with Disabilities Education Act2. The American Legal System reflects the social demand based on epidemiological studies. In the present investigation, we studied the prevalence of attention disorders in Brazil. The sample included 239 students, rated regarding attention problems with a checklist filled by 45 different teachers. As left-handers show greater problems in the impulsive-hyperactivity domain, we investigated the influence of gender on attention problems using handedness as a covariate. Hand preference was assessed by direct observation. A student was classified into the ADD group if he (she) was rated maximum score in at least six questions concerning impulsivity, hyperactivity, and inattention. Sixty-eight students (28% of the total sample) were included in the ADD group. The percentage of males was found to be greater in ADD group as compared to the percentage of males in the normal-control group. The gender effect was not explained by handedness. Our data is similar with other studies. For instance, the rate of ADD symptoms among indigenous students from the Brazilian Amazon was found to be 24.5%. In Brazilian juvenile offenders, the percentage was 33%. The differences with other studies are discussed considering sampling procedures. In accordance with the tradition of the Roman system, we urgently need Federal specific laws to deal with this public health problem. We must convert into specific laws, the Convention on the Rights of Persons with Disabilities (United Nations) that was recently rati

关键词： Handedness Attention-deficit/Hyperactivity Disorder ADD/ADHD Rights of Persons Disabilities