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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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Protopanaxadiol ginsenoside-Rd protects against NMDA receptor-mediated neuronal injury by inhibiting calcineurin-regulated DAPK1 activity

Protopanaxadiol ginsenoside-Rd protects against NMDA recepto...

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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： Ming Shi Chen Zhang Gengyao Hu Xiao Zhang Zhen Xie Dongyun Feng Rui Wu Hui Xu Xuedong Liu Gang Zhao Department of Neurology Xijing HospitalThe Fourth Military Medical University Department of Neurology The Second Artillery General Hospital of PLA Institute of Neurosciences The Fourth Military Medical University

Neuroprotective strategies in the treatment of stroke have been attracting a great deal of attentions. Our previous studies demonstrated that protopanaxadiol ginsenoside-Rd(Rd), a monomer compound extracted from Panax ginseng or Panax notoginseng, had neuroprotective effects against ischemic stroke, which may result from its ability to block Ca2+ overload, a usual consequence of NMDA receptor(NMDAR) overactivation. As an extending study, here we explored whether Rd exerted its neuroprotection as a novel NMDAR blocker. Using a whole-cell patch-clamp technique, we showed that Rd could dose-dependently reduce NMDAR currents in cultured rat cortical neurons(EC50=7.7?M).Moreover, Rd was found to block NMDAR currents by acting on extrasynaptic NMDAR NR2 b subunit. However, cell transfection and radioligand binding assays unexpectedly revealed that Rd actually did not bind to NMDAR channel. Alternatively, it could inhibit the phosphorylation of NR2 b at Ser-1303, a target of death associated protein kinase 1(DAPK1). Cell-based and cell-free enzymatic assays, however, showed that Rd did not inhibit the activity of DAPK1 but that of calcineurin, a key phosphatase for activating DAPK1. Importantly, calcineurin inhibition by its antagonist cyclosporin A could mimic Rd's effects and protect against NMDA-, oxygen glucose deprivation- or transient ischemic stroke-induced neuronal injury. Taken together, our study provided the first evidence that Rd could protect against excitotoxic neuronal injury not result from its serving as a NMDAR blocker, but from its ability to mitigate DAPK1-mediated NR2 B phosphorylation by inhibiting calcineurin activity.

关键词： ginsenoside Rd NMDA receptor phosphorylation DAPK1 calcineurin neuronal injury

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Dynamic changes in hippocampal astrocytes in epileptic brain

Dynamic changes in hippocampal astrocytes in epileptic brain

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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： Preeti Joshi Department of Biophysics National Institute of Mental Health and Neurosciences

Neurons and astrocytes form an intimately connected network in the nervous system and there is compelling evidence demonstrating that neuronal networks alone are not sufficient for information processing, rather astrocytic network is also involved in physiological and pathological signaling in the nervous system. Epilepsy is characterized by synchronous hyperactivity of a group of neurons in the brain. The hyperactivity corresponds to the ictal discharges in electroencephalogram and peroxismal depolarization shifts in single cell recordings. In view of the neuron-astrocyte cross-talk it is imperative that astrocytes may play a role in pathogenesis of epilepsy. Purinergic signaling has emerged as an important mediator of neuron-glia signaling. Extracellular ATP modulates the synaptic activity through P2 Y receptors. We have studied the changes in purinergic receptor expression and function in an in-vivo model of temporal lobe epilepsy. It was observed that significant astrogliosis occurs in specific regions of hippocampus within 1-3 hr of status epilepticus(SE). In SE rats the expression of P2Y1 and P2Y2 receptors was drastically enhanced ascompared to control animals. Immunocytochemistry data revealed that the changes in P2Y1 and P2Y2 receptor expression are localized in astrocytes of stratum radiatum and stratum lacunosum moleculare regions. P2Y1 receptor agonist Me S-ADP inhibited the neuronal hyperactivity in SE rats. On the other hand activation of P2Y2 receptor using UTP appeared to enhance the neuronal hyperactivity. The astrocytic activity manifested as spontaneous Ca2+ oscillations was significantly enhanced in SE rats suggesting hyperactivity in astrocytes. Blockade of the spontaneous Ca2+ activity in astrocytes inhibited the spontaneous action potentials in the CA1 neurons in SE rats implying that the astrocytes certainly modulate the neuronal hyperactivity. Our results demonstrate that the functional characteristics of astrocytes alter at very early stage

关键词： Epilepsy,Neuron-astrocyte communication,P2Y receptors

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Characterization of alpha-synuclein accumulation and aggregation in the enteric nervous system in a transgenic mouse model of Parkinson's disease

Characterization of alpha-synuclein accumulation and aggrega...

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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： Qian-Qian Chen Jia-Yi Li Chong-Bin Zhong Institute of Biotechnology College of Life and Health SciencesNortheastern University Institute of Neuroscience College of Life and Health SciencesNortheastern University

Objective. The enteric nervous system(ENS) control the function of gastrointestinal tract, such as gastrointestinal motility. In Parkinson's disease(PD), in addition to the typical motor symptoms, attentions have been drawn to a number of non-motor symptoms, such as constipation, implying dysfunction of the ENS. Studies have shown that Lewy bodies(LBs), the neuropathological hallmarks of PD, in which α-synuclein is present as its primary protein component, appear in ENS prior to the CNS. It has been suggested that α-synuclein aggregates are generated in the ENS and then retrogradely transported to the CNS via a prion-like mechanism. In the present study, we aim to characterize the age-dependent morphological alterations and aggregation of α-synuclein in the ENS in the gastrointestinal tract of a α-synuclein transgenic mouse model. Materials and Methods We collected gastrointestinal tracts from the stomach to the colon at ages of one week, 1, 3, 6, 9, 18 and 24 months of BAC-α-synuclein-GFP mice after transcardial perfusion with 4% paraformaldehyde in 0.1 M PBS. The small intestines were first studied. Transverse sections were cut with a cryostat(14 μm thick), The native GFP(reflecting α-synuclein transgene expression) and immunohistochemically stained samples were examined with a confocal microscope. Results 1) With age, expression and accumulation of α-synuclein–GFP increase gradually in the submucosal plexus and myenteric plexus. 2) α-synuclein appears highly overlapped with different neuropeptides, such as VIP, n NOS, and Calretinin. n NOS and Calretinin levels increased with age, but not to VIP. 3) The S129-phospho-α-synuclein level was increased with age in transgenic mice, in contrast tothe wildtype mice, reflecting pathological changes of α-synuclein. Conclusion The age-dependent changes and phosphorylation of α-synuclein in the small intestine of BAC-α-synuclein-GFP transgenic mice can provide us a unique model to study the relationship between ENS and PD pa

关键词： enteric nervous system Parkinson's disease α-synuclein phosphorylation protein aggregation

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Functional diversity in human brains based on intrinsic connectivity networks

Functional diversity in human brains based on intrinsic conn...

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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： Cong-Ying Chu Ling-Zhong Fan Tian-Zi Jiang Brainnetome Center Institute of AutomationChinese Academy of Sciences National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of Sciences Key Laboratory for Neuro Information of Ministry of Education School of Life Science and TechnologyUniversity of Electronic Science and Technology of China

A network perspective to understanding the relationship between human brain and behavior has attracted more and more attention recently. There are accumulated evidences to show that the human brain is organized of functional specialized networks. Different networks may be related with special cognitive function and human behavior. Using the networks perspective to describe the functional diversity of human brain could offer a different aspect about the distribution structure of human brain in large scale. Resting-state fMRI is a popular approach used to detect the intrinsic connectivity networks which are also rhythmically showed up in the load state. The independent component analysis is widely adopted to extract the various intrinsic connectivity networks in resting-state. Using ICA approach, we separated twenty components based on resting-state f MRI data which were from Human Connectome Project(100 subjects). After manually choosing the noise components, eighteen components was recognized as significant networks. Based on the participation in different intrinsic connectivity networks, we firstly defined the brain regions which homogeneously participated in different networks using the Components Homogeneity(Co Ho) index. Then, we used the functional diversity index, which measured the anisotropic participation, in the brain regions which possessed the high Co Ho value. High Co Ho value in brain region determined that this brain region homogeneously participated in different networks, which could be viewed as a functional consistent area. Further, using the functional diversity index, we found that the primary cortex including visual cortex and motor area obtained low diversity. Meanwhile, some association cortex significantly participated in different networks, which included the precuneus, inferior parietal lobule, superior frontal gyrus medial orbital. Finally, we analyzed the participation pattern of different brain regions. The region with low diversity only

关键词： functional diversity resting-state fMRI ICA intrinsic connectivity networks

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Depression attenuated allodynia of rat with nerupathic pain via spinal dorsal horn glucucorticoid receptor

Depression attenuated allodynia of rat with nerupathic pain ...

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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： Xiao Wei Yu-Qi Sun Fei Luo Key Laboratory of Mental Health Institute of PsychologyChinese Academy of Sciences The Graduate University Chinese Academy of Sciences

Nowadays, there are still many arguments on the impact of depression on pain sensory. Our previous study improved that depression attenuate allodynia of rats with chronic pain, but the certain neural machenism in spinal dorsal horn remain to be elucidated. Glucocorticoid receptors(GRs), a kind of classical nuclear receptor, distribute in most animal tissues including central neural system. Being accompanied by chaperone protein complex in cytosol, GRs will translocate into nuclear and bind with target DNA to promote transcription after hormones binding. Recent study showed that GRs' function is disabled in hippocampus, prefrontal cortex and other related brain region on depressive-like rats. What's more, peripheral nerve injury up-regulate GRs expression in ipsilateral spinal dorsal horn, which induces allodynia of neuropathic pain. Thus, spinal dorsal horn GRs may play an important role in the inhibiton of allodynia on depressive-like rat with peripheral nerve injury. The present study divided male SD rats into 4 groups: Sham, Olfactory bulbectomy(OB), Spinal nerve ligation(SNL), and OB+SNL, group. First, olfactory bulbectomy surgery was carried on after the open-field and sucrose consumption baseline tests. 14 days later, after the depressive-like behavior being confirmed by open-field and sucrose consumption tests, SNL or Sham surgery was excuted. Mechanical withdraw threshold was tested using Von frey fibers 7 days after SNL surgery. In the end, Western Blot(WB) and immunofluorescence(IF) were carried out to analyise the expression of GRs and astrocyte makers in spinal dorsal horn. The locomotive distance and rearing number in the open-field test were significant up-regulated, meanwhile sucrose consumption score was down-regulated after OB surgery. And ipsilateral mechanical withdraw threshold of OB+SNL group was up-regulated compared with SNL group. Both WB and IF result showed that either OB or SNL group's GRs expression level were obviously increased(***)

关键词： Depression,neuropathic pain,glucocorticoid receptor,spinal dorsal horn

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Medial prefrontal cortex is essential to establishment of pro-social behaviors in rats

Medial prefrontal cortex is essential to establishment of pr...

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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： Yun-Fei Lu Zhen Li Chun-Li Li Yan Wang Rui-Rui Wang Ting He Xiao-Liang Wang Jun Chen Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders Tangdu HospitalThe Fourth Military Medical University Beijing Institute for Brain Disorders

Objective Empathy is an ability to share the feelings of others and plays a fundamental role in the social life of humans. Balanced activation of brain areas that mediate empathy is required for motivating appropriate social behaviors. Our previous research has found that the medial prefrontal cortex(mP FC) played a pivotal role in the empathic process in rats. The present study aims to investigate the roles of the m PFC in pro-social ***(1) A rat was allowed to interact freely within a transparent plastic box for 30 minutes with a cagemate in pain induced by s.c. bee venom(BV) injection and was designated as cagemate observer(CO). 1) Mechanical pain sensitivity of the CO rats that received sham or lesion surgery of the mP FC was measured in isolation and compared to baseline mechanical pain sensitivity measured before the treatments;2) The effects of mP FC lesion on the emotional alterations of CO rats were measured with the open-field test.(2) The effects of m PFC lesion on the social care or social approach to pain were measured with a modified three chamber paradigm. A pair of cagemates was put into cages placed at the two ends of the three-chambered box;one of the rats received a s.c. BV injection before being put into the cage and the other rat was untreated. The social care behavior was presumed if the test rat spent more time in the chamber with its cagemate suffering from pain induced by the BV injection.(3)The effects of mPFC lesion on sociabilityamong cagemates were measured withthe three chamber test. Results The present study showedthat m PFC lesions diminished the bilateral mechanical hypersensitivity in the CO rats. Bilateral lesions of the m PFC eliminated both the self-experienced pain inducedanxiety-like behaviors, which are induced by BV injection, and the vicarious experienced anxiety-like emotional responses in the COrats, which are induced by social interaction with a cagemate in pain. In addition, we found that m PFC lesions impa

关键词： empathy prosocial behavior rodents

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The role of amygdala-prefrontal circuit in electroconvulsive therapy for depression:a resting-state functional magnetic resonance imaging study

The role of amygdala-prefrontal circuit in electroconvulsive...

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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 Wei Yanghua Tian Yongqiang Yu Xiaopeng Hu Yi Dong Yang Chen Panpan Hu Xinglong Hu Kai Wang Department of Neurology the First Affiliated Hospital of Anhui Medical University Department of Radiology the First Affiliated Hospital of Anhui Medical University Anhui Mental Health Center

Background: Electroconvulsive therapy(ECT) is an important treatment option for depression in clinical practice. Compared to antidepressant drugs, ECT has a more rapid onset and is also effective for treatment-resistant depression patients. But ECT could cause cognitive impairment and other side effects, which limit its promotion and application. However, little is known about the underlying therapeutic mechanisms of ECT, even though ECT has been applied in clinical practice for over 70 years. Objective: A lot of studies highlights the role of amygdala-prefrontal circuit in emotion regulation, and current opinion holds that amygdala-prefrontal circuit underlying emotion processing are abnormal in depression. The aim of this study was to observe the change of functional connectivity between amygdala and prefrontal cortex in depression patients before and after ECT, and explore the role of amygdala-prefrontal circuit in therapeutic mechanism of ECT, with the method of resting-state functional magnetic resonance imaging(rs-f MRI). Methods: We set the bilateral amygdale as the seeds respectively, and observe the change of functional connectivity between amygdala and prefrontal cortex in 18 depression patients before and after ECT, compared with 20 healthy controls. Results: The results showed that, compared with depression patients before ECT, the functional connectivity between left amgydala and left lateral frontopolar cortex(BA 10), left amgydala and right lateral frontopolar cortex(BA 10), right amygdala and right medial prefrontal cortex(BA 10) were significantly increased in depression patients after ECT. Compared with healthy controls, the functional connectivity between left amgydala and left lateral frontopolar cortex(BA 10), left amgydala and right lateral frontopolar cortex(BA 10), right amygdala and right medial prefrontal cortex(BA 10) were significantly lower in depression patients before ECT. There was no significant difference of the functional connectiv

关键词： depression electroconvulsive therapy resting-state functional magnetic resonance imaging

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Lentiviral-mediated PTL gene intervention in astrocytic lineage promote neural growth and ameliorate 6-hydroxydopamine-induced cell toxicity in PC12 cells

Lentiviral-mediated PTL gene intervention in astrocytic line...

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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： Ye Zhang Chun-lin Xia Department of Anatomy & Cytoneurobiology lab Medical CollegeSoochow University

Emerging evidence suggests that the phenotypic and functional properties of *** crucial for developing therapies to promote functional recovery after neural injury. Pancreatic triglyceride lipase(PTL), an enzyme known to promote digestion and absorption of lipids, appeared as a critical regulator of the proliferation of astrocytes and the recovery of neurological outcomes after traumatic brain injury(TBI) in our previous observation. In addition, recent reports have shown that many parkinson's disease(PD)-associated gene products may operate through cholesterol zone of plasma membrane in astrocytes. However, little is known about the exact role of this lipid gene in astrocytic lineage till now, which may have implications for understanding the pathogenesis of neurodegenerative diseases and their related therapies. Herein, we sought to investigate the potential effects of lentiviral-mediated PTL gene intervention in cortical astrocytes(type1/2 astrocytes, T1As/T2As) on primary neural growth and neuronal differentiated PC12 cells injuried by 6-hydroxydopamine(6-OHDA). The results revealed that T1 As stably overexpressing PTL showed significantly enhanced cell proliferation. By contrast, PTL knock-down by si RNA in T2 As led to a strong inhibition of the cell viability. Cortical neurons, co-cultured with T1 As overexpressing PTL, also displayed significantly enhanced growth and migration capability. Intriguingly, the processes in these neural cells appeared to thicken and gather to show column-like growth in a few days. Immunostaining detection further showed high positiverate of axonal markers within these thickened neurofilaments. Additionally, we found high mesencephalic astrocyte-derived neurotrotrophic factor(MANF) expression level only in T1 As overexpressing PTL group and its co-cultured neurons. We found that pretreatment by co-cultured with PTL-transduced astrocytes(especially T1As) notably attenuated 6-OHDA-induced neuronal damage, but increased the

关键词： pancreatic triglyceride lipase astrocytic lineage gene intervention 6-hydroxydopamine PC12 cells

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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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