BACKGROUND: Neurons expressing gamma-aminobutyric acid (GABA) play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tub...BACKGROUND: Neurons expressing gamma-aminobutyric acid (GABA) play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus (TMn), with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE: To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING: Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS: Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups(n = 5): control, ventrolateral preoptic area (VLPO) lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma (St. Louis, USA). METHODS: Four electroencephalogram screw electrodes were implanted into the skull at a frontal region (two) and parietal bones (two) on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette (10–20 mm tip diameter) containing ibotenic acid solution (10 nmol/L) was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline (10 nmol/L), a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES: Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit (Micro1 401 mk2) and Data collection software (Spike Ⅱ). RESULTS: VLPO lesion induced an increased duration of wakefulness (W, 13.17%) and light slow-wave sleep (SWS1, 28.9%), respectively. Deep slow-wave sleep (SWS2, 43.74%) and paradoxical sleep (PS, 44.07%) were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion (P 〈 0.01). Microinjection of bicuculline into the TMn following VLPO lesion at 10:00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% (P 〈 0.01) and 50.97% (P 〈 0.01), respectively. In addition, SWS2 and PS were decreased by 68.08% (P 〈 0.01) and 39.92% (P 〈 0.05), respectively, compared with prior to VLPO lesion. CONCLUSION: The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive (sleepiness) via local circuit to directly inhibit histaminergic neurons.展开更多
Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty o...Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.展开更多
A growing number of studies have identified sex differences in response to general anesthesia;however,the underlying neural mechanisms are unclear.The medial preoptic area(MPA),an important sexually dimorphic structur...A growing number of studies have identified sex differences in response to general anesthesia;however,the underlying neural mechanisms are unclear.The medial preoptic area(MPA),an important sexually dimorphic structure and a critical hub for regulating consciousness transition,is enriched with estrogen receptor alpha(ERa),particularly in neuronal clusters that participate in regulating sleep.We found that male mice were more sensitive to sevoflurane.Pharmacological inhibition of ERαin the MPA abolished the sex differences in sevoflurane anesthesia,in particular by extending the induction time and facilitating emergence in males but not in females.Suppression of ERαin vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females.Furthermore,ERα.knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia.Collectively,MPA ERαpositively regulates the activity of MPA GABAergic neurons in males but not in females,which contributes to the sexdifference of mice in sevoflurane anesthesia.展开更多
The preoptic area (POA) is located in the most anterior part of the hypothalamus and is bordered dorsally by the anterior commissure and anteroventrally by the nucleus of the diagonal band of Broca[1]. Accumulating ...The preoptic area (POA) is located in the most anterior part of the hypothalamus and is bordered dorsally by the anterior commissure and anteroventrally by the nucleus of the diagonal band of Broca[1]. Accumulating evidence from developmental neurobiology suggests, however, that the POA may be a separate entity from hypothalamus, and may actually be part of the basal telencephalon[2,3]. Both the hypothalamus and POA are highly complex and heterogeneous areas, containing multiple nuclei, each of which has specific fundamental functions for survival. Among these, the POA contains nuclei involved in the regulation of blood osmolality and temperature (the median preoptic nucleus), sleep (the ventrolateral preoptic and suprachiasmatic nuclei), ovulation (gonadotropin-releasing hormone neurons scattered mainly in the ventral part of the POA), male sexual behavior (the medial preoptic nucleus), and parental behavior (the central part of the medial POA, cMPOA).展开更多
Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neuro...Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neurons in hypothalamus and the medial preoptic area (MPO). Electrical stimulation of MPO can cause a rise in secretion展开更多
Many research works through out the world show that the preoptic area(POA) is a region concerned with analgesia. Electric stimulation to this region could enhance markedly pain threshold and exert an analgesic effect....Many research works through out the world show that the preoptic area(POA) is a region concerned with analgesia. Electric stimulation to this region could enhance markedly pain threshold and exert an analgesic effect. Central 5-hydroxytryptamine (5-HT) plays an important role in pain mediation. Acupuncture could accelerate the synthe-展开更多
本实验在家兔双侧视前区内注入6-羟基多巴胺(6-OH-DA,4μg/每侧),选择性损毁该区儿茶酚胺(CA)神经末梢后,观察对针刺镇痛的影响。实验结果表明,注药后第二、四天,针刺镇痛效应较针前或对照组均有明显提高。注药后第十天,针刺镇痛效应基...本实验在家兔双侧视前区内注入6-羟基多巴胺(6-OH-DA,4μg/每侧),选择性损毁该区儿茶酚胺(CA)神经末梢后,观察对针刺镇痛的影响。实验结果表明,注药后第二、四天,针刺镇痛效应较针前或对照组均有明显提高。注药后第十天,针刺镇痛效应基本恢复到对照组水平。用甲醛诱发荧光组织化学法显示视前区 CA 末梢,可见6-羟基多巴胺组的 CA 末梢明显减少。结果提示,视前区 CA 含量减少有利于针刺镇痛作用。展开更多
基金the National Natural Science Foundation of China, No. 30670677
文摘BACKGROUND: Neurons expressing gamma-aminobutyric acid (GABA) play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus (TMn), with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE: To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING: Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS: Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups(n = 5): control, ventrolateral preoptic area (VLPO) lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma (St. Louis, USA). METHODS: Four electroencephalogram screw electrodes were implanted into the skull at a frontal region (two) and parietal bones (two) on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette (10–20 mm tip diameter) containing ibotenic acid solution (10 nmol/L) was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline (10 nmol/L), a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES: Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit (Micro1 401 mk2) and Data collection software (Spike Ⅱ). RESULTS: VLPO lesion induced an increased duration of wakefulness (W, 13.17%) and light slow-wave sleep (SWS1, 28.9%), respectively. Deep slow-wave sleep (SWS2, 43.74%) and paradoxical sleep (PS, 44.07%) were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion (P 〈 0.01). Microinjection of bicuculline into the TMn following VLPO lesion at 10:00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% (P 〈 0.01) and 50.97% (P 〈 0.01), respectively. In addition, SWS2 and PS were decreased by 68.08% (P 〈 0.01) and 39.92% (P 〈 0.05), respectively, compared with prior to VLPO lesion. CONCLUSION: The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive (sleepiness) via local circuit to directly inhibit histaminergic neurons.
文摘Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.
基金This workwas supported by,the National Natural Science Foundation of China(82071554 and 81620108012).
文摘A growing number of studies have identified sex differences in response to general anesthesia;however,the underlying neural mechanisms are unclear.The medial preoptic area(MPA),an important sexually dimorphic structure and a critical hub for regulating consciousness transition,is enriched with estrogen receptor alpha(ERa),particularly in neuronal clusters that participate in regulating sleep.We found that male mice were more sensitive to sevoflurane.Pharmacological inhibition of ERαin the MPA abolished the sex differences in sevoflurane anesthesia,in particular by extending the induction time and facilitating emergence in males but not in females.Suppression of ERαin vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females.Furthermore,ERα.knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia.Collectively,MPA ERαpositively regulates the activity of MPA GABAergic neurons in males but not in females,which contributes to the sexdifference of mice in sevoflurane anesthesia.
文摘The preoptic area (POA) is located in the most anterior part of the hypothalamus and is bordered dorsally by the anterior commissure and anteroventrally by the nucleus of the diagonal band of Broca[1]. Accumulating evidence from developmental neurobiology suggests, however, that the POA may be a separate entity from hypothalamus, and may actually be part of the basal telencephalon[2,3]. Both the hypothalamus and POA are highly complex and heterogeneous areas, containing multiple nuclei, each of which has specific fundamental functions for survival. Among these, the POA contains nuclei involved in the regulation of blood osmolality and temperature (the median preoptic nucleus), sleep (the ventrolateral preoptic and suprachiasmatic nuclei), ovulation (gonadotropin-releasing hormone neurons scattered mainly in the ventral part of the POA), male sexual behavior (the medial preoptic nucleus), and parental behavior (the central part of the medial POA, cMPOA).
文摘Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neurons in hypothalamus and the medial preoptic area (MPO). Electrical stimulation of MPO can cause a rise in secretion
文摘Many research works through out the world show that the preoptic area(POA) is a region concerned with analgesia. Electric stimulation to this region could enhance markedly pain threshold and exert an analgesic effect. Central 5-hydroxytryptamine (5-HT) plays an important role in pain mediation. Acupuncture could accelerate the synthe-
文摘本实验在家兔双侧视前区内注入6-羟基多巴胺(6-OH-DA,4μg/每侧),选择性损毁该区儿茶酚胺(CA)神经末梢后,观察对针刺镇痛的影响。实验结果表明,注药后第二、四天,针刺镇痛效应较针前或对照组均有明显提高。注药后第十天,针刺镇痛效应基本恢复到对照组水平。用甲醛诱发荧光组织化学法显示视前区 CA 末梢,可见6-羟基多巴胺组的 CA 末梢明显减少。结果提示,视前区 CA 含量减少有利于针刺镇痛作用。