Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats / 대한마취과학회지

BACKGROUND: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported. METHODS: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured. RESULTS: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats. CONCLUSIONS: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

Intraventricular injection of 5,7-dihydroxytryptamine alters neuronal activity of neurons in the medial prefrontal cortex of rat / 生理学报

The present study is aimed to investigated the firing activity of pyramidal neurons and interneurons in the medial prefrontal cortex (mPFC) in rats with bilateral intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) by using in vivo extracellular recording. The results showed that the injection of 5,7-DHT reduced the 5-hydroxytryptamine (5-HT) levels in the mPFC and dorsal raphe nucleus in the rats. The firing rate of mPFC pyramidal neurons in rats with 5,7-DHT injection was significantly higher than that of normal rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing, while the injection decreased the firing rate of mPFC interneurons and changed the firing pattern of the interneurons towards a more irregular. These results indicate that the lesions of the serotonergic neurons lead to the changes in the firing activity of mPFC pyramidal neurons and interneurons, suggesting that serotonergic system plays an important role in the regulation of the neuronal activity in the mPFC.

Effect of serotonin depletion on seizures learning-memory in pilocarpine-induced epileptic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between serotonin (5-HT) and epilepsy and the mechanism of learning-memory in pilocarpine (PILO)-induced epileptic rats after 5,7-dihydroxytryptamine (5,7-DHT) microinjection in median raphe nucleus.</p><p><b>METHODS</b>Adult S D rats were randomly divided into 3 groups: PILO group, PILO+ 5,7-DHT group, vehicle control group; PILO group was divided into two groups by status epilepticus (SE): PILO + SE group and PILO - SE group. The rats' seizures and cortex electroencephalography (EEG) were observed by video EEG. The rats' spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic neuron in raphe nuclei was observed by immunohistochemistry.</p><p><b>RESULTS</b>After treatment of 5,7-DHT (PILO + 5,7-DHT group), the success rate, the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved. Compared with the control group, the number of serotonergic neuron in raphe nuclei was decrease in PILO + SE group (P < 0.05). Moreover, it's extremely decrease in PILO + 5,7-DHT group (P < 0.01). Compared with control group, the mean escape latency was prolonged, the times of crossing target was decreased and the retention time in target zone was shortened in PILO + SE group (P < 0.05), but there was no significant difference between PILO + SE group and PILO + 5,7-DHT group.</p><p><b>CONCLUSION</b>Depletion of serotonin may facility the rats' epileptic seizures, but we could not interpret which may cause epileptic rats' cognitive deficit.</p>

Increased subthalamic neuronal activity after dorsal raphe nucleus lesion by 5,7-dihydroxytryptamine in the rat / 生理学报

In vivo extracellular recordings were made in the subthalamic nucleus (STN) of intact control rats and rats with 5,7-dihydroxytryptamine (5,7-DHT) -produced lesion of dorsal raphe nucleus (DRN). The results showed that the firing rate of STN neurons in control rats and DRN-lesioned rats were (6.93+/-6.55) Hz and (11.27+/-9.31) Hz, respectively, and the firing rate of DRN-lesioned rats significantly increased when compared to the control rats (P<0.01). In control rats, 13% of STN neurons discharged regularly, 46% irregularly and 41% in bursts. In DRN-lesioned rats, 9% of STN neurons discharged regularly, 14% irregularly and 77% in bursts, the percentage of STN neurons firing in bursts was obviously higher than that of the control rats (P<0.01). In addition, the mean interspike interval coefficient of variation of STN neurons in control rats and DRN-lesioned rats were (0.05+/-0.04) and (0.11+/-0.09), respectively. The mean interspike interval coefficient of variation of DRN-lesioned rats was significantly higher than that of the control rats (P<0.001). These results show that the firing rate and the bursting pattern rate of neurons in STN of DRN-lesioned rats increase significantly, suggesting that DRN inhibits the neuronal activity of the subthalamic neurons in the intact rat.

Modelo molecular unificado de estrés oxidativo en las enfermedades de Alzheimer y Parkinson / Unified molecular model of stress oxidative in diseases Alzheimer's and Parkinson's

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.