RESUMEN
Coriandrum sativum (coriander) is an annual herb of the Apiaceae family and has been used as a traditional remedy. Here we examined whether heated leaf extract of coriander decreases the concentrations of heavy metals in tissues. Male ddY mice were given a drinking water containing 0.25% of heated leaf extract of coriander for 8 weeks. Eight weeks after the intake, the concentrations of zinc, iron, copper, arsenic, and cadmium were measured in the liver and kidney. The intake of coriander did not modify the concentrations of all heavy metals tested in the liver, but decreased the concentrations of iron, arsenic, and cadmium in the kidney. Because heavy metals can induce oxidative stress, the effect of coriander intake on hydrogen peroxide-induced oxidative stress was compared between slices from the kidney and liver. The slices were immersed in Ringer solution containing 100 µM hydrogen peroxide and aminophenyl fluorescein (APF), a probe for detecting reactive oxygen species (ROS). APF fluorescence was markedly increased in the control kidney slices, while the increase was completely blocked in kidney slices from coriander intake group. In contrast, APF fluorescence was also markedly increased in the control liver slices, while the increase was not blocked by coriander intake. The present study indicates that intake of coriander leaf extract contributes to powerful resistance to oxidative stress in the kidney, probably via decreased concentrations in heavy metals. It is likely that decrease in arsenic concentration to the detection limit is a major factor for the resistance.
Asunto(s)
Coriandrum/química , Metales Pesados/análisis , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Animales , Arsénico/análisis , Arsénico/metabolismo , Cadmio/análisis , Cadmio/metabolismo , Hierro/análisis , Hierro/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metales Pesados/metabolismo , Ratones , Extractos Vegetales/química , Hojas de la Planta/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The basal levels of extracellular Zn2+ are in the range of low nanomolar concentrations and less attention has been paid to Zn2+, compared to Ca2+, for synaptic activity. However, extracellular Zn2+ is necessary for synaptic activity. The basal levels of extracellular zinc are age-dependently increased in the rat hippocampus, implying that the basal levels of extracellular Zn2+ are also increased age-dependently and that extracellular Zn2+ dynamics are linked with age-related cognitive function and dysfunction. In the hippocampus, the influx of extracellular Zn2+ into postsynaptic neurons, which is often linked with Zn2+ release from neuron terminals, is critical for cognitive activity via long-term potentiation (LTP). In contrast, the excess influx of extracellular Zn2+ into postsynaptic neurons induces cognitive decline. Interestingly, the excess influx of extracellular Zn2+ more readily occurs in aged dentate granule cells and intracellular Zn2+-buffering, which is assessed with ZnAF-2DA, is weakened in the aged dentate granule cells. Characteristics (easiness) of extracellular Zn2+ influx seem to be linked with the weakened intracellular Zn2+-buffering in the aged dentate gyrus. This paper deals with the impact of synaptic Zn2+ signaling on cognition and its decline in comparison with synaptic Ca2+ signaling.
Asunto(s)
Cognición/fisiología , Sinapsis/metabolismo , Zinc/metabolismo , Animales , Encéfalo/metabolismo , Trastornos del Conocimiento/fisiopatología , Humanos , Modelos NeurológicosRESUMEN
Glutamatergic neuron activity and/or the modification of the activity with glucocorticoids are closely linked to synaptic Zn2+ dynamics as well as synaptic Ca2+ dynamics. The dynamic crosstalk of synaptic Zn2+ signaling to intracellular Ca2+ signaling via calcium channels is involved in synaptic plasticity such as long-term potentiation (LTP) and cognitive activity. The influx of extracellular Zn2+ into postsynaptic neurons, which is closely linked to glutamate signaling in the synaptic cleft, is critical for cognitive activity. However, excess intracellular Zn2+ signaling induced by excess glutamatergic neuron activity is involved in not only cognitive decline in neurological disorders but also stress-induced cognitive decline. On the other hand, it has been recognized that excess Ca2+ influx into postsynaptic neurons induces neuronal death, while the involvement of excess intracellular Ca2+ signaling in cognitive decline is poorly understood. Understanding of synaptic Zn2+ dynamics, which are modified by glutamate and glucocorticoid signaling, may be meaningful to prevent Zn2+-mediated cognitive decline. This paper summarizes the current knowledge on Zn2+ dynamics under changing synaptic environment and its impact on cognitive decline.
Asunto(s)
Calcio/química , Trastornos del Conocimiento/metabolismo , Glucocorticoides/química , Ácido Glutámico/química , Zinc/química , Animales , Encéfalo/metabolismo , Cognición , Hipocampo/metabolismo , Humanos , Potenciación a Largo Plazo , Neuronas/metabolismo , Transducción de Señal , SinapsisRESUMEN
Hippocampal Zn2+ homeostasis is critical for cognitive activity and hippocampus-dependent memory. Extracellular Zn2+ signaling is linked to extracellular glutamate signaling and leads to intracellular Zn2+ signaling, which is involved in cognitive activity. On the other hand, excess intracellular Zn2+ signaling that is induced by excess glutamate signaling is involved in cognitive decline. In the hippocampal formation, the dentate gyrus is the most vulnerable to aging and is thought to contribute to age-related cognitive decline. The layer II of the entorhinal cortex is the most vulnerable to neuronal death in Alzheimer's disease. The perforant pathway provides input from the layer II to the dentate gyrus and is one of the earliest affected pathways in Alzheimer's disease. Medial perforant pathway-dentate granule cell synapses are vulnerable to either excess intracellular Zn2+ or ß-amyloid (Aß)-bound zinc, which induce transient cognitive decline via attenuation of medial perforant pathway LTP. However, it is unknown whether the vulnerability to excess intracellular Zn2+ is involved in region-specific vulnerability to aging and Alzheimer's disease. To discover a strategy to prevent short-term cognitive decline in normal aging process and the pre-dementia stage of Alzheimer's disease, the present paper deals with vulnerability of medial perforant pathway-dentate granule cell synapses to intracellular Zn2+ dyshomeostasis and its possible involvement in differential vulnerability to aging and Alzheimer's disease in the hippocampal formation.
Asunto(s)
Giro Dentado/metabolismo , Corteza Entorrinal/metabolismo , Zinc/metabolismo , Envejecimiento , Enfermedad de Alzheimer/metabolismo , Animales , Giro Dentado/química , Corteza Entorrinal/química , Hipocampo/metabolismo , Homeostasis , HumanosRESUMEN
A portion of zinc concentrates in the synaptic vesicles in the brain and is released from glutamatergic (zincergic) neuron terminals. It serves as a signaling factor (in a form of free Zn2+). Both extracellular Zn2+ signaling, which predominantly originates in Zn2+ release from zincergic neuron terminals, and intracellular Zn2+ signaling, which is often linked to extracellular Zn2+ signaling, are involved in hippocampus-dependent memory. At mossy fiber-CA3 pyramidal cell synapses and Schaffer collateral-CA1 pyramidal cell synapses, which are zincergic, extracellular Zn2+ signaling leads to intracellular Zn2+ signaling and is involved in learning and memory. At medial perforant pathway-dentate granule cell synapses, which are non-zincergic, intracellular Zn2+ signaling, which originates in the internal stores containing Zn2+, is involved in learning and memory. The blockade of Zn2+ signaling with Zn2+ chelators induces memory deficit, while the optimal amount range of Zn2+ signaling is unknown. It is possible that the degree and frequency of Zn2+ signaling, which determine the increased Zn2+ levels, modulates learning and memory as well as intracellular Ca2+ signaling. To understand the precise role of synaptic Zn2+ signaling in the hippocampus, the present paper summarizes the current knowledge on Zn2+ signaling at zincergic and non-zincergic synapses in the hippocampus in cognition and involvement of zinc transporters and zinc-binding proteins in synaptic Zn2+ signaling.