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E3 ligase Nrdp1 increases ischemia induced primary rat cerebral cortical neurons injury via downregulation of parkin

E3 ligase Nrdp1 increases ischemia induced primary rat cereb...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yuan Zhang Ting Wang Ce Zhang Wei-Ping Li Wen-Lan Liu The Central Laboratory Shenzhen Second People's Hospital Shenzhen University 1st Affiliated Hospital Department of Neurosurgery Shenzhen Second People's Hospital

Neuregulin receptor degradation protein-1(Nrdp1) is an E3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth, inflammation and apoptosis, including Erb B3, MyD 88, TBK1 and BRUCE. However, the effect of Nrdp1 on ischemic brain injury in vitro has not yet been investigated. Previously, we found that not only oxygen-glucose deprivation(OGD) induced injury markedly upregulated Nrdp1 expression in primary rat cerebral cortical neurons, but also the expression of Nrdp1 was significantly increased in cerebral cortex in a rat model of middle cerebral artery occlusion. To further elucidate the role of Nrdp1 in OGD-induced neuronal injury, primary rat cerebral cortical neurons were infected with adenoviral constructs expressing Nrdp1 wild-type and Nrdp1-si RNA genes. Increased Nrdp1 expression enhanced OGD-induced neuron apoptosis and oxidative stress as compared with the green fluorescent protein(GFP)control;thus, these effects were attenuated by overexpression of Nrdp1-si RNA. Furthermore, the mechanisms underlying these effects were associated with the downregulation of an Nrdp1 substrate, parkin, which depletion preceded development of neuron cell death. Together, these data provide the first in vitro evidence for an important role for Nrdp1 in regulating OGD-induced neuronal injury, which was accompanied by parkin ubiquitination and degradation by the activation of Nrdp1. Nrdp1 may constitute a new therapeutic target for ameliorating ischemic brain injury.

关键词： ischemic stroke neuronal injury Nrdp1 E3 ligase parkin

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Hyperactivity of lateral habenula contributes to depressive symptoms induced by hypothyroidism in rats

Hyperactivity of lateral habenula contributes to depressive ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Qiang Zhang Shuai Yang Xiao Feng Liu Ji Cheng Li Hua Zhao Department of Physiology Key Laboratory of PathobiologyMinistry of EducationCollege of Basic Medical SciencesJilin University Department of Thyroid Surgery Neuroscience Research CenterFirst Hospital of Jilin University

The depression-like behavior could be observed both in hypothyroidism rats and patients, suggesting that changes in thyroid hormone levels are closely associated with mental disorders and decreased(5-hydroxytryptamine, 5-HT)5-HT level in some brain regions could also be found in hypothyroidism rats with depression-like behavior. However, how hypothyroidism affects the central 5-HT system is unclear. Tha lateral habenula(LHb) palys an important role in the pathogenesis of depression. It is not only closely linked to the 5-HT system, but also with the thyroid *** purpose of our research is to the role of the LHb in the onset of depressive-like behavior by thyroidectomy as a link between 5-HT system and thyroid system. Force swimming test(FST) and open–field test(OFT) were performed to measure the behavior changes between thyroidectomy(TD) and sham groups. Expression of β calmodulin-dependent protein kinase type II(β Ca MKII),in tha LHb, Cytochrome C oxidase(COX) activity in the LHb and dorsal raphe nucleus(DRN) and 5-HT content in the DRN were assayed to evaluate the activities of the LHb and DRN. We found that TD rats showed an obvious depression-like behavior as increased immobile time, decreased climbing time in FST and decreased movement distance in OFT, which could be reversed by inducing a lesion in the LHb. Compared to the sham group, the neuronal activity in TD rats was higher in the LHb and lower in the DRN, β CaM KII in the LHb was up regulated. 5-HT levels of the DRN were declined in TD rats compared to that of in the shamgroup, which could be turned over by inducing a lesion in the LHb. we conclude that depression-like behavior could be induced by hypothyroidism in TD rats, which is attributed to the decreased 5-HT levels in the DRN due to the inhibitory effect on the DRN neurons from the excited LHb.

关键词： hypothyroidism depression-like behavior lateral habenula dorsal raphe nucleus serotonin force swimming test

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Hijacking dorsal raphe to improve metabolism and moods via BDNF gene transfer

Hijacking dorsal raphe to improve metabolism and moods via B...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jianbo Xiu Rongrong Han Zeyue Liu Shu Liu Yan Shen Qi Xu The State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences & Neurosciences CenterChinese Academy of Medical Sciences & Peking Union Medical College

For a long time, researches on energy metabolism and emotion regulation are divided in their respective fields. However, epidemiological investigations suggest that metabolic diseases like obesity and mood disorders such as depression have significant comorbidities;furthermore, they influence each other by enhancing the risk of the other ones, for which there are no clear neurobiological mechanisms. Both brain derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) can regulate metabolisms in the hypothalamus and moods in the limbic system. As the biggest nucleus of the central 5-HT system, dorsal raphe projects substantially into the hypothalamus and the limbic system. Based on that feature and our preliminary data, we proposed that BDNF overexpressed in the dorsal raphe improve metabolism and moods simultaneously. We used adeno-associated virus, a gene therapy vector, to get in vivo expression of BDNF in dorsal raphe, through which we analyzed the effects on energy metabolism and emotion regulation in mice. Our study found that BDNF can promote the metabolism rate of mice fed with normal diet. In high fat diet feeding conditions, BDNF can resist the high fat diet induced obesity and high blood glucose level. BDNF had remarkable curative effect on obesity and high blood glucose level of diet-induced obesity(DIO) mouse model. BDNF also can reduce the triglyceride, cholesterol and leptin levels in the serum of mice. In addition, BDNF can significantly relieve the abnormality in metabolism of db/db mice. In the chronic unpredictable mild stress(CUMS) mice model of depression, our study shows that higher expression of BDNF through dorsal raphe can significantly improve the depression and anxiety like behavior in mice. The expression of BDNF in hippocampus can significantly improve the depression like behavior induced by restraint stress in mice but had no effect on the energy metabolism, which further proved that BDNF in the dorsal raphe that play a role in ene

关键词： dorsal raphe BDNF energy metabolism emotion regulation

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Exploring the role of kalirin7 in mouse dopaminergic neurons in response to cocaine

Exploring the role of kalirin7 in mouse dopaminergic neurons...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Mingxing Li Shucheng An Xin-Ming Ma College of Life Science Brain Research InstituteShaanxi Normal University University of Connecticut Health Center Department of NeuroscienceStem Cell Institute

Objective Cocaine addiction is a chronic relapsing neurological disorder associated with severe medical and psychosocial complications. Despite decades of research, no effective treatment is available for cocaine addiction. To better understand the underlying mechanisms is a key for developing an efficient therapy. Our previous studies show that kalirin7, a major kalirin isoform in adult rodent brain, plays a key role in the formation of dendritic spines in the GABAergic medium spiny neurons of the nucleus accumbens following cocaine exposure. Dopaminergic(DA) neurons in the ventral tegmental area(VTA) play a crucial role in drug reward circuit and addiction. However, the role of kalirin7 in the DA neurons of the VTA and the effect of cocaine on kalirin7 in these DA neurons are not known. The aims of this study were to address these questions. Methods: Wild type mice were given cocaine or saline for 7 consecutive days, and locomotor sensitization elicited by cocaine was evaluated. Coronal sections through the VTA were biolistically labeled with the lipophilic tracer 1,1'-dioctadecyl-3,3,3',3' –tetramethy- lindocarbocyanine perchlorate(Di I) using a gene gun. Dendritic spines were visualized using a Zeiss LSM510 confocal microscope. Double immunostaining with antibodies specific to rabbit kalirin7 and mouse tyrosine hydroxylase was used to determine kalirin7 expression in the DA neurons. Results Preliminary results showed that mice were sensitive to locomotor sensitizing effects of cocaine, and cocaine treatments resulted in an increase in kalirin7 expression accompanying by an increase in spine density in the DA neurons. Conclusion These results suggest an important role of Kalirin7 in the formation of dendritic spines in the VTA DA neurons following cocaine exposure.

关键词： cocaine addiction,Kalirin7,dendritic spine locomotor sensitization ventral tegmental area,dopamine

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The effects of short-term sleep deprivation on the neuronal functions in the spatial learning and memory-related brain regions

The effects of short-term sleep deprivation on the neuronal ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jie Yan Jia-Li Wang Mei-Lan Xie Chao Li Chao He Zhi-An Hu Department of Physiology Third Military Medical University

Sleep is known as a brain state that increases the clearance of neurotoxic waste products and promotes learning-related synapse formation and maintenance. Numerous studies reported that sleep deprivation(SD) causes impairment of cognitive performance. However, the neural mechanisms underlying this phenomenon remain elusive. Here, we administrated the animals with short term SD that frequently happens in our daily life and explored their influence on neuronal functions in the cognition-related brain regions. In the prefrontal cortex(PFC), we found 4 h SD reduced the afterhyperpolarization(AHP) of evoked action potentials and consequently led to an increase in the slope of firing frequency–current curve and a decrease in frequency adaptation. The SD-induced alterations of AHP was mediated by voltage-gated Ca2+ channels and can be reversed post recovery of sleep. In addition, western blotting was performed to assess the expression levels of ionotropic α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptor subunits and the N-methyl-d-aspartate(NMDA) glutamate receptor subunits. In hippocampus, down regulation of surface Glu A1 and Glu N2 A surface expression were observed in 4 h and 8 h SD groups. However, surface expression level of GluA 2, GluA 3, Glu N1 and Glu N2 B were significantly up-regulated in 8 h-SD rats when compared to the 4 h-SD rats. In parallel with the complex changes in cortical intrinsic excitability and AMPA and NMDA receptor subunit expressions, we found the SD impaired rat spatial working memory in 30-sec-delay T-maze task. Together, these results indicate that sleep loss enhances neuronal intrinsic activity in the PFC and alters the relative expression levels of the AMPA and NMDA receptors in hippocampus, which might consequently influence the synaptic strength and capacity for plasticity. These findings provide useful cues to explain the SD with short duration-induced impairment in cognition.

关键词： Sleep deprivation Prefrontal cortex Glutamate receptor Hippocampus

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Resting-state functional connectivity between the dorsal anterior cingulate cortex and anterior insula/thalamus is associated with risky decision-making in nicotine addicts

Resting-state functional connectivity between the dorsal ant...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zhengde Wei Nannan Yang Lizhuang Yang Ying Wang Long Han Rujing Zha Ying Liu Peng Zhang Yifeng Zhou Xiaochu Zhang Key Laboratory of Brain Function and Disease Chinese Academy of SciencesSchool of Life SciencesUniversity of Science & Technology of China Provincial Hospital Affiliated to Anhui Medical University State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of Sciences School of Humanities & Social Science University of Science & Technology of China Center of Medical Physics and Technology Hefei Institutes of Physical ScienceCAS Centers for Biomedical Engineering University of Science & Technology of China

Nicotine addiction is associated with risky behaviors and with abnormalities in local brain areas related to risky decision making, including the dorsal anterior cingulate cortex(d ACC), anterior insula(AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. Thus far, it is unclear whether circuit-level abnormalities lead to risky decision making in nicotine addicts. In the current study, we used task-based functional magnetic resonance imaging(f MRI) and examined the resting-state functional connectivity(RSFC) to study how connectivity between the d ACC, insula, and thalamus influence risky decision making in nicotine addicts. We found that an increase in risky decision making was associated with stronger nicotine dependence and stronger RSFC between the d ACC and right AI(rA I), the d ACC and thalamus, the d ACC and left AI(lA I), and the r AI and lA I, but the level of the risky decision making was not associated with risk level-related local activation. Furthermore, the severity of nicotine dependence was positively correlated with RSFC between the d ACC and r AI and between the d ACC and thalamus but was not associated with risk level-related local activation. Importantly, the d ACC-r AI and dA CC-thalamus couplings fully mediated the effect of nicotine-dependent severity on risky decision making. These results suggest that circuit-level connectivity may be a critical neural link between abnormally risky decision making and nicotine addiction.

关键词： decision making risky behavior nicotine addiction salience network fMRI RSFC

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Locus Coeruleus projectome and its online regulation of visual processing

Locus Coeruleus projectome and its online regulation of visu...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Changmei Zhang Weiyu Chen Wenjie Du Rongwei Zhang Jiulin Du Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain ScienceShanghai Institutes for Biological SciencesChinese Academy of Sciences Graduate School University of Chinese Academy of Sciences Guizhou Key Laboratory of Anesthesia and Organ Protection Zunyi Medical College

Objective Neuromodulators play profound modulatory influence on a diversity of brain functions ranging from sensory processing, perception, cognition, to motor behavior. Norepinepherine(NE) is one of the major neuromodulators in the central nervous system. The Locus Coeruleus(LC) neurons are the main source of NE, and extend widespread innervations into almost all brain regions to modulate many physiological functions,including sleep and arousal, vigilance, and detection and processing of salient sensory information. However, it is unclear about the projection pattern of individual LC neurons and their specific function. Taking advantage of the optical transparency and multiple genetic tools of larval zebrafish, we aim to delineate the anatomical structure of every LC neuron and to examine their modulatory effect on visual processing in the optic tectum, one of the main target regions of LC neurons. We are also interested in the online interaction of visual-induced activities between LC and tectal neurons. Methods We use single-cell electroporation technique to label single LC neuron with fluorescent proteins and perform in vivo whole-cell recording of LC and tectal neurons to examine their synaptic activities. Results(1) A single LC neuron of larval zebrafish extends global arborization into most of brain areas, including the forebrain, optic tectum, cerebellum, hindbrain and even spinal cord;(2) LC neurons receive visual information from the optic tectum and exhibit burst-like responses to visual stimuli;(3) Local application of NE in the optic tectum can inhibit light-induced and spontaneous responses in some tectal neurons while increase spontaneous activities in other tectal neurons. Conclusion LC neurons are important for the online regulation of visual processing in the optic tectum, and modulate the output of visual behavior.

关键词： Locus coeruleus zebrafish larvae projectome optic tectum online regulation

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Melatonin attenuates methamphetamine-induced locomotor sensitization and Sirt1 expression

Melatonin attenuates methamphetamine-induced locomotor sensi...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jin-Tao Wu De-Xiao Zhu Hui WANG Hai-Li Liu Qian Wang Jing Zhang Jin-Hao Sun Departmunt of Anatomy Shandong UniversitySchool of Medicine

Objective Locomotor sensitization is characterized as the enhancement of locomotor activities after exposure to psychostimulants. Such kind of sensitization can be incubated during some time of withdrawal, which is termed incubation of sensitization. Although great amount of investigations have focused on the robust augment of locomotor distances induced by psychostimulants, the underlying mechanisms of these phenomena remain elusive. Melatonin is a known "hormone of darkness" secreted mainly by the pineal gland. Evidences indicate that melatonin is effective in treating depression and sleep disorders, which are the leading withdrawal symptoms found in methamphetamine(MA) addicts. Moreover, melatonin can attenuate MA-induced neurotoxicity. Furthermore, melatonin is considered to be a Sirt1 inhibitor, whereas recent studies suggest Sirt1 plays a critical role in drug addiction. Here, we suppose that melatonin treatment during the incubation of sensitization should be effective in suppressing the final expression of locomotor sensitization and the effect may be associated with the alteration of Sirt1 expression. Methods The mice were treated daily with MA(1 mg/kg) for seven consecutive days, and locomotor activities were recorded on day one and seven. Then 14 days of the incubation of sensitization was followed, during which the mice were treated with melatonin(10 mg/kg) or vehicle daily. After that, on day 22 the mice were challenged with MA and the expressionof locomotor sensitization was recorded. Finally, the brains of mice were dissected out and the prefrontal cortex(PFC) and nucleus accumbens(NAc) were harvested, the proteins were extracted and the expression of Sirt1 was determined by western blotting. Results(1) MA exposure remarkably enhances the locomotor activities of mice.(2) Melatonin treatment during the incubation of sensitization significantly attenuates the expression of sensitization.(3) Melatonin treatment suppresses Sirt1 over-expression caused by

关键词： melatonin methamphetamine incubation sensitization nucleus accumbens Sirt1

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Chinese Speech Decoding Using Intracranial EEG

Chinese Speech Decoding Using Intracranial EEG

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Bo Hong Department of Biomedical Engineering School of MedicineTsinghua University

A finite set of phonetic units is used in human speech, but how our brain recognizes these units from speech stream is still largely unknown. The revealing of this neural mechanism may lead to the development of new types of speech brain computer interfaces and computer speech recognition systems. In this study, we used intracranial EEG(iE EG) signal from human cortex to decode Chinese phonetic units during the perception of continuous speech. By exploring the time-frequency features, we identified i EEG electrodes that have selective response to specific Chinese phonemes. High-gamma power of these electrodes was further combined to separate sets of phonemes into clusters. The clustered organization largely coincided with phonological categories defined by discriminative features, similar as that has been found in English(Mesgarani et al, 2014). These findings were incorporated into a decoding framework of Chinese phonemes clusters and achieved consistent accuracies higher than chance level. Additionally, in tonal languages, like Chinese, lexical tone also serves as a key feature to provide contrast in word meaning. Behavior studies suggest that Mandarin Chinese tone is categorically perceived(Wang 1976;Xu et al. 2006). However, the neural mechanism underlying Mandarin tone perception is still poorly understood. In this study, an Oddball paradigm was designed by selecting two standard-deviant stimulus pairs with same physical distance but different category labels, among the synthesized tones with continuously varying pitch contours. Using i EEG recording over human auditory cortex, high temporal and spatial resolution cortical neural signals were used for the first time to investigate the cortical processing of lexical tone. We found distinct neural responses to the two standard-deviant tone pairs, and the difference increased from low to high-level electrodes along the hierarchy of auditory processing. In the two dimensional neural space, cross-category neural dis

关键词： Chinese Speech Decoding Using Intracranial EEG

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Exploring timescales of adaptation mechanisms along the visual-processing hierarchy

Exploring timescales of adaptation mechanisms along the visu...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Gaoxing Mei Xue Dong Min Bao Key Laboratory of Behavioral Science Institute of PsychologyChinese Academy of Sciences

Recent work has indicated that adaptation is controlled by multiple mechanisms acting at different timescales, but their neural underpinnings remain largely unknown. Here we explored this issue with two psychophysical experiments. We first used a "deadaptation" procedure(Bao, Fast, Mesik, & Engel, 2013) to investigate contrast adaptation under either the binocular or monocular adaptation condition. Thresholds were measured with a spatial 4-AFC contrast detection task, tracked by a one-down-one-up staircase. The "deadaptation" duration was individually set, based upon a pilot test where 5 minutes of adaptation to high contrast was followed by 280 s of deadaptation. Interestingly, the effects of adaptation failed to completely decay to the baselines under the monocular condition in 21 out of 37 subjects, but succeeded under the binocular condition in everyone. For the 16 subjects whose adaptation's effects could deadapt to the baselines, their data showed spontaneous recovery in the post-tests, demonstrating that multiple mechanisms controlled adaptation in both conditions. Critically, it took longer to deadapt to the baseline(p<.001) in the monocular(84s) than the binocular condition(51s). Given the larger proportion of monocular neurons activating in the binocular condition, these results suggest that longer-term mechanisms reside at the binocular processing stage. To compare the timescales of mechanisms spanning wider in the visual processing hierarchy, we modified Hancock and Pierce's(2008) paradigm to track the decay of TAE in 15 subjects after adaptation to either the compound gratings(curvature) or component gratings. An exponential function was fit to the timecourses following adaptation, which revealed slower time constant(p<.05) for the compound(149s) than the component(113s) adaptation condition. This indicates longer-term mechanisms in the mid-level(e.g. V4) than the early visual areas. Our findings imply that cortical mechanisms for controlling adaptation

关键词： multiple mechanisms contrast adaptation tilt aftereffect

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