ABSTRACT
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent progressive neurodegenerative diseases affecting millions of people in the world. Because a significant percentage of patients share common clinical and pathological features from both entities, this may indicate the existence of a common pathological mechanism. Based on in vitro and in situ data, authors proposed an unified molecular oxidative stress model induced by dopamine (DA), 6-hydroxydopamine (6-OHDA); 5,6 & 5,7-dihydrytryptamine (5,6 & 5,7 DHT); amyloid beta 25-35 (Aß25-35), and metals [e. g. iron (Fe2+), copper (Cu2+), zinc (Zn2+), manganese (Mn2+)], as a possible explanation of neural loss in AD/PD overlapping cases. This hypothesis might contribute to a better understanding of the pathophysiology cascades of both disorders, and also support the notion that oxidative stress generated by H2O2 represent an essential molecule of intracellular signalization leading to cell death. Taken together, these findings might allow a better rational approach to therapeutic design that rescue, delay or retard cell death in patients suffering from those deteriorating disorders.
La enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP) son los trastornos neurodegenerativos progresivos que afectan con mayor frecuencia a millones de personas en el mundo. Dado que un porcentaje significativo de pacientes comparten características clínicas y patológicas de ambas entidades, esto podría indicar la existencia de un mecanismo patológico común. Con base en estudios in vitro e in situ, los autores proponen un modelo molecular unificado de estrés oxidativo en EA y EP, inducido por los estímulos tóxicos, la dopamina (DA), la 6- hidroxidopamina (6-OHDA), la 5,6-dihidroxitriptamina (5,6-DHT), la 5,7-dihidroxitriptamina (5,7-DHT), el beta-amiloide 25-35 (Aß[25-35]) y los metales (v. gr. hierro [Fe2+], cobre [Cu2+], cinc [Zn2+], manganeso [Mn2+]) como posible explicación a la pérdida neuronal en algunos casos mixtos con EA/EP. Esta hipótesis podría contribuir a una mejor comprensión de las cascadas fisiopatológicas en ambos desórdenes y valida la idea de que el estrés oxidativo generado por el peróxido de hidrógeno (H2 O2) representa una molécula fundamental de señalización de muerte celular. En conjunto, estas investigaciones permitirían un mejor acercamiento racional en los diseños terapéuticos que rescaten, detengan o retarden los procesos de deterioro neuronal en los pacientes que padecen estas devastadoras patologías.
Subject(s)
Humans , Parkinson Disease , 5,6-Dihydroxytryptamine , 5,7-Dihydroxytryptamine , Alzheimer Disease , Dopamine , Oxidopamine , Cell Death , Copper , Amyloid , MetalsABSTRACT
The metabolic alteration of 5-HT in four different regions of rat brain and plasma was studied under acute and chronic heat stress. A generalised elevation of 5-HT in all the brain regions along with high plasma level was observed in animals subjected to 4 hour heat stress at 38 degrees C. Such elevation of brain 5-HT may be due to entry of plasma 5-HT into the brain owing to breakdown of blood-brain barrier (BBB). In heat adapted rats, where BBB remained unaffected, no increase in brain 5-HT was observed, rather a significantly low level was maintained both in plasma and brain tissue.
Subject(s)
5,6-Dihydroxytryptamine/pharmacology , Acute Disease , Adaptation, Physiological/physiology , Alanine/analogs & derivatives , Animals , Blood-Brain Barrier/physiology , Brain/metabolism , Chronic Disease , Female , Hot Temperature/adverse effects , Male , Rats , Rats, Inbred Strains , Serotonin/blood , Stress, Physiological/bloodABSTRACT
The effect of restraint stress (1, 2 and 4 hr) on cannabis-induced catalepsy, was investigated in rats. Restraint stress produced a time-related-potentiation of the cataleptic effect of a sub-cataleptic dose of cannabis. Stress (4 hr)-induced potentiation of cannabis catalepsy was attenuated after pretreatment of the animals with drugs known to decrease central 5-HT and prostaglandin activity, but was unaffected by metyrapone, an inhibitor of endogenous corticoid synthesis. The results suggest the involvement of 5-HT and prostaglandins in restraint stress-cannabis interaction. The results have been discussed in the light of earlier investigations, from this laboratory, indicating increased rat brain 5-HT and prostaglandin activity, following restraint stress, and possible 5-HT mediation in central effects of prostaglandins. It is suggested that restraint stress first enhances rat brain prostaglandins, which in its proposed role as the first mediator' of stress, activates the serotonergic system in this species. This prostaglandin 5-HT link, thus mediates the observed potentiating effect of restraint stress on cannabis catalepsy.