Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced di...Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.展开更多
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
Estrogen receptor a is widely distributed in the rat brain, but the tissue- or target-specificity of the estrogen receptor a gene promoters remains unknown. In the present study, we used transgenic rats expressing enh...Estrogen receptor a is widely distributed in the rat brain, but the tissue- or target-specificity of the estrogen receptor a gene promoters remains unknown. In the present study, we used transgenic rats expressing enhanced green fluorescent protein under the control of the estrogen receptor a 0/B promoter to examine expression driven by this promoter in two significant nuclei that regulate cardiovascular activity, the area postrema and the nucleus tractus solitarius. Immunohistochemistry showed that enhanced green fluorescent protein-labeled cells were distributed in the area postrema and the nucleus tractus solitarius of both female and male transgenic rats, and a neural network of enhanced green fluorescent protein-positive fibers was seen between the area postrema and the nucleus tractus solitarius. The number of enhanced green fluorescent protein-labeled cells in the area postrema of female rats was significantly higher than in the males, but no significant difference was found in the number of enhanced green fluorescent protein-labeled cells in the nucleus tractus solitarius. The sex differences in the number of enhanced green fluorescent protein-labeled cells in the area postrema was not affected after ovariectomy or 1713-estradiol benzoate treatment in adult rats. Our results suggest that the effects of estrogen in the area postrema are related to the expression of estrogen receptor a under the control of the 0/B promoter, and changes in the sex hormone environment in the adult period do not affect estrogen receptor a expression in the area postrema or the nucleus tractus solitarius.展开更多
基金the grant of Science and Technology Bureau of Liaoning Province,No. 20041033
文摘Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.
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.
基金supported by a Japan-China Sasakawa Medical Fellowship from the Japan China Medical Association
文摘Estrogen receptor a is widely distributed in the rat brain, but the tissue- or target-specificity of the estrogen receptor a gene promoters remains unknown. In the present study, we used transgenic rats expressing enhanced green fluorescent protein under the control of the estrogen receptor a 0/B promoter to examine expression driven by this promoter in two significant nuclei that regulate cardiovascular activity, the area postrema and the nucleus tractus solitarius. Immunohistochemistry showed that enhanced green fluorescent protein-labeled cells were distributed in the area postrema and the nucleus tractus solitarius of both female and male transgenic rats, and a neural network of enhanced green fluorescent protein-positive fibers was seen between the area postrema and the nucleus tractus solitarius. The number of enhanced green fluorescent protein-labeled cells in the area postrema of female rats was significantly higher than in the males, but no significant difference was found in the number of enhanced green fluorescent protein-labeled cells in the nucleus tractus solitarius. The sex differences in the number of enhanced green fluorescent protein-labeled cells in the area postrema was not affected after ovariectomy or 1713-estradiol benzoate treatment in adult rats. Our results suggest that the effects of estrogen in the area postrema are related to the expression of estrogen receptor a under the control of the 0/B promoter, and changes in the sex hormone environment in the adult period do not affect estrogen receptor a expression in the area postrema or the nucleus tractus solitarius.
