Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hip...Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.展开更多
In present work,the effects of acupuncturing Renzhong（GV 26）and Zusanli（ST 36）on the neuronal activity of Locus Coeruleus（LC）in rats were observed and compared.The resultsindicated that the central mechanism o...In present work,the effects of acupuncturing Renzhong（GV 26）and Zusanli（ST 36）on the neuronal activity of Locus Coeruleus（LC）in rats were observed and compared.The resultsindicated that the central mechanism of promoting blood pressure（BP）by acupuncturing Renzhongwas related to the activity of LC;the influence of acupuncturing Renzhong on neuronal activity of LC was more obvious than that of acupuncturing Zusanli;and there was relative speciality between the acupoints.展开更多
Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in ...Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.展开更多
Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostri...Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased sig...展开更多
The locus coeruleus(LC) has been studied in major depressive disorder(MDD) and bipolar disorder(BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytoche...The locus coeruleus(LC) has been studied in major depressive disorder(MDD) and bipolar disorder(BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin.We found significantly increased tyrosine hydroxylase(TH) in the LC of MDD patients—thus validating the method—but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.展开更多
The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.T...The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.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
In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently ...In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently estrogen receptors have been known to be located in the locus coeruleus(LC), where noradrenergic(NE) fibres terminate in the hypothalamus arising from cell bodies. The discharge rate of NE-ergic neurons in LC can be increased by electrical stimulation of MPO in a female rat at estrus stage, and decreased at diestrus stage. These studies help us to infer that VMN might have some modulation influence on NE-ergic neurons in LC. In order to study the pattern activities展开更多
The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) respon...The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) responses from FN cells. The majority of responsive cells showed an inhibitory response with a latency of less than 10 ms. Injection of α adrenoreceptor antagonists phentolamine (ⅳ) could block the inhibitory response of FN cells to the LC stimulation, but propranolol (ⅳ), a β adrenoreceptor antagonist, could not. These results suggest that LC-cerebellar noradrenergic afferent fibers may be involved in the cerebellar sensorimotor integration process by exerting their modulatory action on the cerebellar nuclear cells’ activities.展开更多
基金supported by the National Natural Science Foundation of China, No. 81100663the Scientific Research Funds of the Health Department of Hunan Province, No.120303+1 种基金Hunan Provincal Natural Science Foundation of China, No. 13JJ3058a grant from the Scientific Research Program of Hunan Provincial Higher Education Institutes, No. 11C0829
文摘Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
文摘In present work,the effects of acupuncturing Renzhong（GV 26）and Zusanli（ST 36）on the neuronal activity of Locus Coeruleus（LC）in rats were observed and compared.The resultsindicated that the central mechanism of promoting blood pressure（BP）by acupuncturing Renzhongwas related to the activity of LC;the influence of acupuncturing Renzhong on neuronal activity of LC was more obvious than that of acupuncturing Zusanli;and there was relative speciality between the acupoints.
基金supported by the Corbett Estate Fund(62285-531021-41800,to EW)the Helen Vosburg McCrillus Plummer and Robert Edward Lee Plummer,Jr.Chair Fund(to JHH).
文摘Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.
基金supported by the Foundation of Science and Technological Program of Shaanxi Province,China (No. 2007K15-G1).
文摘Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased sig...
基金supported by the National Key R&D Program of China (2016YFC1306700)the National Natural Science Foundation of China (91332102 and 31271130)
文摘The locus coeruleus(LC) has been studied in major depressive disorder(MDD) and bipolar disorder(BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin.We found significantly increased tyrosine hydroxylase(TH) in the LC of MDD patients—thus validating the method—but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.
基金supported by the National Natural Science Foundation of China(31971058 and 31571174)the Youth Fund for Scientific and Technological Research in Higher Education Institutions of Hebei Province(QN2019019)the Youth Science and Technology Talent Support Program of Natural Science in Hebei Medical University(CYQD201907)。
文摘The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.
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In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently estrogen receptors have been known to be located in the locus coeruleus(LC), where noradrenergic(NE) fibres terminate in the hypothalamus arising from cell bodies. The discharge rate of NE-ergic neurons in LC can be increased by electrical stimulation of MPO in a female rat at estrus stage, and decreased at diestrus stage. These studies help us to infer that VMN might have some modulation influence on NE-ergic neurons in LC. In order to study the pattern activities
文摘The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) responses from FN cells. The majority of responsive cells showed an inhibitory response with a latency of less than 10 ms. Injection of α adrenoreceptor antagonists phentolamine (ⅳ) could block the inhibitory response of FN cells to the LC stimulation, but propranolol (ⅳ), a β adrenoreceptor antagonist, could not. These results suggest that LC-cerebellar noradrenergic afferent fibers may be involved in the cerebellar sensorimotor integration process by exerting their modulatory action on the cerebellar nuclear cells’ activities.
