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1.
Brain Res Bull ; 139: 67-80, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29421245

RESUMEN

BACKGROUND: Brain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown. AIMS: to study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved. METHODS: A total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed. RESULTS: Compared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes. CONCLUSION: T2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Trastornos del Conocimiento/tratamiento farmacológico , Exenatida/uso terapéutico , Nicotinamida Fosforribosiltransferasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Trastornos del Conocimiento/etiología , Diabetes Mellitus Tipo 2/complicaciones , Modelos Animales de Enfermedad , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo
2.
Drug Discov Ther ; 5(3): 136-43, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22466243

RESUMEN

Vincristine (VCR) is a potent anticancer drug, but neurotoxicity is one of its most important dose-limiting toxicities. In this study, we investigated the neurotoxic effect of VCR, the possible mechanisms and the role of erythropoietin (EPO) in the protection against VCR-induced neurotoxicity in a rat model. The neurotoxicity of VCR and protective effect of EPO were examined using the tail flick test and by recording electrophysiological characteristics in isolated sciatic nerve. To elucidate the underlying mechanisms, mRNA expression of N-methyl-D-aspartate (NMDA) receptor, an index of glutamate excitotoxicity, and calcitonin gene-related peptide (CGRP), an important regulator of vascular tone, were measured in both spinal cord and sciatic nerves using an RT-PCR method. After intraperitoneal injection at a dose of 150 µg/kg three times weekly for five consecutive weeks, VCR significantly decreased the latency of tail withdrawal reflex, the amplitude of maximum compound action potential (MCAP) and chronaxie, and prolonged the duration of action potential (AP) and relative refractory period (RRP), but it had no effect on conduction velocity. VCR increased NMDA receptor expression and decreased CGRP expression. Forty µg/kg of EPO improved all VCR-induced changes, except chronaxie, while a higher dose of 80 µg/kg reversed all parameters and its effect was more prominent on tail flick test latency and NMDA receptor expression. These results suggested that VCR might cause increased nerve excitability and induce a state of glutamate excitotoxicity through enhancing NMDA receptor expression and diminishing CGRP expression, thus resulting in axonal degeneration. EPO had an obvious neuroprotective effect probably through decreasing NMDA receptor expression and increasing CGRP expression both centrally and peripherally.

3.
East Mediterr Health J ; 11(5-6): 1124-7, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16761685

RESUMEN

The Egypt Human Development Report 2003 does not take account of the impact of the environment on human development indicators. A case study was made in one village in El-Montaza district, Alexandria governorate, Egypt. The environmental indicators used for calculating the human development index were access to safe water, access to sanitation and environment surrounding the house. The human development index for this village decreased from 0.622 to 0.595 after adjustment for environmental factors.


Asunto(s)
Salud Ambiental/normas , Indicadores de Salud , Desarrollo Humano , Recolección de Datos , Interpretación Estadística de Datos , Economía , Escolaridad , Egipto/epidemiología , Encuestas Epidemiológicas , Vivienda/normas , Humanos , Esperanza de Vida , Salud Rural/estadística & datos numéricos , Saneamiento/normas , Encuestas y Cuestionarios , Abastecimiento de Agua/normas
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