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Neuronal Mechanisms of Borneol in the Treatment of Impaired Awake Activity by Long-term Continous Operations

Author: XueLi
Tutor: ZhouHong
School: Third Military Medical University
Course: Pharmacology
Keywords: Long continuous operation Borneol Treadmill Unit discharge Prefrontal cortex Histamine Norepinephrine 5 - HT Pyrilamine Prazosin Litan mianserin Rats Lateral hypothalamus area c-Fos orexin-A High performance liquid chromatography - electrochemical
CLC: R285
Type: Master's thesis
Year: 2006
Downloads: 84
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Abstract

More common in real life, the long-time continuous operation, such as long-distance drivers or pilots of continuous driving, military operations. Work as well as mandatory these super circadian cycle of sleep or less sleep work has had a serious impact on the operator's behavior and cognitive function, and greatly reduces the efficiency. Therefore, how to improve the efficiency of long continuous operation personnel has long been an important issue to be solved in occupational medicine today. My room to the traditional small animal treadmill device based, in combination with its own set of 48-hour continuous operation mode, in order to establish a long-term continuous operation model. The model successfully simulated a variety of influencing factors in the process of long-term continuous operation, show that long continuous operation can significantly damage in rats awakening ability and cognitive function. On this basis, we studied the role of borneol intervention awakening ability damage, results showed that borneol can to a certain extent on the reversal of long continuous operation awakening ability and cognitive function damage in rats, but the the borneol role neural mechanisms not been elucidated. Borneol were first observed in rat prefrontal cortex excitatory and clarify its neural mechanisms. Then study the lateral hypothalamic area orexin-A long-term continuous operation, the expression of c-Fos and borneol intervention effect, thereby further understanding of the the borneol role of nerve mechanism. The results are as follows:, borneol, borneol on the rat prefrontal cortex electrical activity of excitatory mechanisms (a) electrical excitatory effects on rat prefrontal cortex (PFC) by PFC neurons Unit discharge frequency changes on cortical excitability level. Studies have shown that the rat PFC neurons spontaneous discharge with a single uneven beam tufted and three mixed discharge mode discharge activities mixed. Units discharge frequency (5min average) 7.45 ± 1.67Hz (n = 48), the discharge time of 3 ~ 3.5ms. Were injected via the indwelling stomach tube after the high dose of borneol (1.2g/5ml/kg and 2.0/5ml/kg), the unit discharge frequency gradually increased, the 25 35min when the most obvious (n = 12, P <0.05; n = 12, P <0.01), high-dose borneol higher degree of higher than the dose borneol (n = 12, P <0.01), while the low dose borneol (0.4g/5ml/kg) had no significant change (n = 12, P> 0.05). The results indicate that the The borneol discharge of rat PFC neurons units in excitatory effect in a dose - dependent. The improvement may be related to the continuous operation when prompted borneol on long of rats damaged awakening ability improve PFC neuronal excitability. (B) borneol rat prefrontal cortical electrical excitability role of neural mechanisms. The histamine H ₁ receptor antagonist mepyramine (pyrilamine) borneol excited prefrontal cortex neurons electrical activity giving pyrilamine 60μg inhibitory effect of lateral ventricle, compared with before administration after administration neuron units discharge frequency gradually slowed down (n = 12, P <0.05). Subsequent experiments, pyrilamine 60μg icv micro-injection pretreatment gastric tube into the high-dose borneol, before and after administration neuron unit discharge frequency no significant change (n = 12, P> 0.05). The results show that the high dose borneol PFC neurons discharge frequency increases pyrilamine blocked, the prompt histamine H ₁ receptor pathway involved in cortical excitatory effect of borneol. 2 norepinephrine α ₁ receptor antagonist prazosin hydrochloride (prazosin) borneol excited the mild suppression effect Prazosin 63μg icv micro injected rat prefrontal cortex neurons electrical activity, PFC the neuron unit discharge frequency before and after no significant change (n = 12, P> 0.05). Micro-inject pretreatment Prazosin 63μg icv injected high doses by stomach tube borneol, after administration of firing rate can still be increased significantly (n = 12, P <0.05), but the increase in the degree of borneol alone excited to be lower than the high dose effect, the second significant differences (n = 12, P <0.05). The results showed that the high dose borneol PFC neurons discharge frequency increases partially blocked by prazosin, suggesting α ₁ receptor pathway to some extent involved in cortical excitatory effect of borneol norepinephrine. 3.5-hydroxytryptamine (5-HT ₂) receptor antagonist Litan mianserin (ritanserin) mild the borneol excitement prefrontal cortex neuronal activity of the inhibitory effect of micro injection Ritanserin 40μg icv before administration compared to the neuron unit discharge frequency slowed after administration (n = 12, P <0.05). Subsequent experiment, the lateral ventricle after the micro injected pretreatment through a gastric tube into the high-dose borneol given 40μg ritanserin administered after neuronal firing frequency can still significantly increased (n = 12, P <0.05), but increased the degree lower than high dose borneol separate excitatory effect significant difference between the two (n = 12, P <0.05). The results show that the high dose borneol PFC neurons discharge frequency increases be ritanserin partially blocked, suggesting that 5 - HT receptor pathway (5-HT ₂) to some extent involved in the cortex of borneol excitatory effect. Second, borneol on long continuous operation rat prefrontal cortex neurotransmitter levels (a) long-term continuous operation rat prefrontal cortex neurotransmitter levels change in this experiment, using high-performance liquid chromatography - electrochemical methods determination of the long continuous operation prefrontal cortex noradrenaline (NA), dopamine (DA) and 5 - hydroxytryptamine (5-HT) neurotransmitter content changes. The results showed that, the treadmill paraffin group to the content of norepinephrine in the prefrontal cortex brain regions were lower (P <0.05), while there was no significant decline in dopamine and 5 - HT (P> 0.05). The results suggest that long-term continuous operation, the animals awakening ability and cognitive function decline may go with the prefrontal cortex related to the decline in the level of norepinephrine. (B) borneol on long continuous operation after continuous 48h job affect rat frontal cortex neurotransmitter levels in the rat forebrain, homemade gastric tube orally borneol paraffin oil or paraffin oil solution, measured after two hours above the prefrontal cortex neurotransmitter content. Than treadmill paraffin oil group than the treadmill borneol group NA and 5-HT content was significantly higher (n = 5, P <0.05), while the DA had no significant change (n = 5, P> 0.05). The results showed that borneol on long jobs of rats damaged awakening ability continuous improvement may be associated with an increased prefrontal cortex NA and 5-HT levels. , Borneol on long continuous operation when the rat lateral hypothalamic area orexin-A and c-Fos expression (a) long-term continuous operation of rat lateral hypothalamic area using c-Fos and orexin-A expression changes The immunohistochemical staining treadmill wax, and unused treadmill paraffin rats. The results showed that: the treadmill group rat lateral hypothalamic area expression of c-Fos and orexin-A were reduced (n = 4, P <0.05). Results prompted a long continuous operation, the decline of the awakening ability and cognitive function in rats may be reduced with the lateral hypothalamus region of the c-Fos and orexin-A expression. (B) borneol on the rat lateral hypothalamic area impact study of the expression of c-Fos and orexin-A long-term continuous operation after borneol intervention in rats lateral hypothalamus area of ??c-Fos and orexin-A long-term continuous operation expressed. The results showed that the treadmill borneol group rat lateral hypothalamic area c-Fos expression of orexin-A group (n = 4, P <0.05) higher than the treadmill paraffin. Not run station borneol rats c-Fos expression was significantly higher than not treadmill paraffin oil group (n = 4, P <0.01), and orexin-A and not treadmill paraffin oil group was no significant difference (n = 4, P> 0.05). The results suggest that, borneol long continuous operation rat lateral hypothalamic area damaged awakening capacity improvement may borneol caused increased expression of c-Fos and orexin-A related. In summary, the results of this study show that, first, borneol rat prefrontal cortex excitability role system is directly related to the excitatory effect of subcortical histamine, noradrenaline and 5 - HT system related part. Second, norepinephrine and 5 - the level of serotonin in the prefrontal cortex in rats, which may be involved in the intervention role of borneol borneol increase the long continuous operation. Third borneol enables long continuous operation increased rat lateral hypothalamic area expression of c-Fos and orexin-A, which may be directly related to the awakening ability to improve damaged and borneol.

Neuronal Mechanisms of Borneol in the Treatment of Impaired Awake Activity by Long-term Continous Operations

Abstract

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