Abstract:Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into the CA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway.

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	1. Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
	Yin Xi,Song Li,Geng Xuhong,Gao Yuan,Wang Jiechao,Li Jianli,Shi Haishui,Hou Yanning
	Biology 08 October 2015
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	Abstract:Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into the CA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway.
	TO cite this article:Yin Xi,Song Li,Geng Xuhong, et al. Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory[OL].[ 8 October 2015] http://en.paper.edu.cn/en_releasepaper/content/4656959


	2. Acute effects of TGFβ1 on neuronal excitability and possible involvement in the pain of rats with chronic pancreatitis
	Zhang Xiaoyu,Zheng Hang,Jiang Xinghong,Xu Guang-Yin
	Biology 06 May 2015
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	Abstract:Background: Transforming growth factor beta1 (TGFβ1) is upregulated in chronic inflammation, where it plays a key role in wound healing and promoting fibrosis. However, the role of TGFβ1 in nociceptive processing in primary sensory neurons remains unclear. The aim of this study is to investigate whether TGFβ1 plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. Methods: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Pancreatic hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGFβ1 on acutely isolated pancreas-specific DRG neurons. Results: Intrathecal injection of TGFβ receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGFβ1 application depolarized the membrane potential and caused firing activity of pancreas-specific DRG neurons. TGFβ1 application also reduced the rheobase, hyperpolarized action potential threshold and increased the number of action potentials evoked by current injection of pancreas-specific DRG neurons. TGFβ1 application increased the concentration of intracellular calcium of pancreas-specific DRG neurons, which was inhibited by TGFβ receptor I antagonist but not by TRPV1 receptor antagonist. Furthermore, intrathecal injection of TGFβ1 produced abdominal hyperalgesia in health rats. Conclusions: These results suggest that TGFβ1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGFβ receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
	TO cite this article:Zhang Xiaoyu,Zheng Hang,Jiang Xinghong, et al. Acute effects of TGFβ1 on neuronal excitability and possible involvement in the pain of rats with chronic pancreatitis[OL].[ 6 May 2015] http://en.paper.edu.cn/en_releasepaper/content/4641932

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	3. Induction of Rhythmic Movement in the L12 Segment of Gekko gecko by L-Glutamic Acid
	Wang Wenbo,Cui Guanqi,Liu Lei,Cai Lei,Guo Ce
	Biology 04 January 2015
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	Abstract:The lizard Gekko gecko has become an ideal model for bio-inspired robot because of its excellent three dimensional obstacle-free locomotion ability. Vertebrates show outstanding motion control capability. Their rhythmic locomotion is modulated by the central pattern generator (CPG) in spinal cord. The spinal preparation of gecko in vivo was made with the adaptor designed. The preliminary research on CPG neural network of gecko was carried out by the method of recording common peroneal nerve under the condition of L12 segment of lumbar enlargement being micro stimulated by different concentrations of glutamate. Rhythmic discharge of common peroneal nerve could be induced following the stimulation on L12 segment with 10mM glutamate. From the statistical analysis of the signal acquainted, it has been found that the amplitude and frequency of discharge depend on the stimulation concentration.
	TO cite this article:Wang Wenbo,Cui Guanqi,Liu Lei, et al. Induction of Rhythmic Movement in the L12 Segment of Gekko gecko by L-Glutamic Acid[OL].[ 4 January 2015] http://en.paper.edu.cn/en_releasepaper/content/4626322


	4. High efficiency of neuron differentiation from neural stem cells by monolayer culturing by mash1>
	Zhang Qian,Zhou Mingming,Wu Xiaobo,Zhang Jie,Cao Yuelong,Ding Daofang,Zhan Hongsheng
	Biology 10 July 2013
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	Abstract:Efficient generation of neuroprogenitor or neurons is necessary for the development of autologous cell therapies for the treatment of neurological disease. Neural stem cells (NSCs) represent a valuable resource for both research and regenerative medicine due to their ability to propagate indefinitely in vitro and to spontaneously differentiate into neurons. However, several weeks are often required for neuronal generation, and the percentage of resulting neurons is often relatively low. In this study, we adopted the initiative methods in China. Primary neurosphere monolayer from rat EC stem cells was isolated by selecting a single colony during passage, more than 95% of neural stem cells formed the neurosphere monolayer only after 1 day of differentiation, and purified homogenous NSCs proliferated throughout the entire plate after six passages. This monoclonic culture assay on neurosphere monolayer successfully generated high-contented neuron with high purity. In addition, the effect of serum concentration on neuronal production was also characterized in this study. These novel methods will be valuable for both research purposes as well as for clinical therapies.
	TO cite this article:Zhang Qian,Zhou Mingming,Wu Xiaobo, et al. High efficiency of neuron differentiation from neural stem cells by monolayer culturing by mash1>[OL].[10 July 2013] http://en.paper.edu.cn/en_releasepaper/content/4550749


	5. Histamine excites rat superior vestibular nuclear neurons via postsynaptic H1 and H2 receptors in vitro
	ZHUANG Qianxing,WU Yonghui,WU Guanyi,ZHU Jingning,WANG Jianjun
	Biology 05 March 2013
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	Abstract:The superior vestibular nucleus (SVN), which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca2+/high-Mg2+ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine (2-PyEA) and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via post-synaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.
	TO cite this article:ZHUANG Qianxing,WU Yonghui,WU Guanyi, et al. Histamine excites rat superior vestibular nuclear neurons via postsynaptic H1 and H2 receptors in vitro[OL].[ 5 March 2013] http://en.paper.edu.cn/en_releasepaper/content/4522573


	6. Histamine excites neurons of the inferior vestibular nucleus in rats by activation of H1 and H2 receptors
	PENG Shiyu,ZHUANG Qianxing,HE Yecheng,ZHU Jingning,WANG Jianjun
	Biology 26 February 2013
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	Abstract:By using brain slice preparations and extracellular recordings, the effect of histamine on spontaneous firing activities of neurons in the inferior vestibular nucleus (IVN), a key structure responsible for integration of vestibular, multisensory, and cerebellar inputs, in rats was investigated. Perfusing slices with histamine (1-10 μM) elicited an excitatory response on IVN neurons. The responses were not blocked by low Ca2+/high Mg2+ medium, indicating a direct postsynaptic effect of the amine. Furthermore, the histamine-induced excitation was partially blocked by selective histamine H1 receptor antagonist mepyramine (1 μM) and H2 receptor antagonist ranitidine (1 μM), respectively. Co-application of mepyramine and ranitidine nearly totally antagonized the histamine-induced excitation. Additionally, both selective H1 receptor agonist 2-pyridylethylamine (30-300 μM) and H2 receptor agonist dimaprit (10-100 μM) effectively mimicked the excitatory action of histamine on IVN neurons. Moreover, selective H4 antagonist JNJ7777120 (10 μM) and agonist VUF8430 (30-300 μM) had no effect on IVN neurons. These results demonstrate that histamine excites IVN neurons via postsynaptic H1 and H2 rather than H4 receptors, and suggest that the central histaminergic system actively modulate all four major vestibular nuclei including the IVN and may subsequently influence the vestibular nuclei-related reflexes and functions.
	TO cite this article:PENG Shiyu,ZHUANG Qianxing,HE Yecheng, et al. Histamine excites neurons of the inferior vestibular nucleus in rats by activation of H1 and H2 receptors[OL].[26 February 2013] http://en.paper.edu.cn/en_releasepaper/content/4523979


	7. The molecular mechanism analysis based on the gene expression profiling of memory enhancement in NR2B transgenic mice
	LI Chunxia,DONG Suzhen,WANG Huimin,HU Yinghe
	Biology 18 December 2010
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	Abstract:NMDA receptor plays a pivotal role in different forms of memory. The NR2B transgenic (Tg) lines, in which the NMDA receptor function is enhanced via the NR2B subunit transgene in neurons of the forebrain, exhibit larger long term potentiation (LTP) in the forebrain and superior performances in learning and memory. However, its molecular mechanisms remain to be elucidated. Gene expression profiling results revealed that many genes involved in neurotransmission, signal transduction, cellular structure/cytoskeleton, hormone signaling and transcription were altered in Tg mice. Specially, our microarray and real-time PCR analysis demonstrated that intracellular calcium channel proteins, RyR1 and RyR3, as well as functional related proteins such as Hrc and Trdn were up-regulated, indicating that they may play important roles in cognitive improvement of Tg mice. Our results also showed that Homer-1c protein which was increased in Tg mice, forms complex with RyR protein in mice brain, suggesting that Homer-1c might be an important modulator on both intracellular calcium signaling and overall neuronal signaling by interacting with NMDA receptor and RyR simultaneously. Moreover, we found that the expression of phospho-CREB, c-fos, Egr2 and Egr4 were up-regulated in Tg mice using the Western blot and Real-time PCR technologies, respectively. The present studies have provided important clues for the molecular mechanism of learning and memory enhancement in Tg mice.
	TO cite this article:LI Chunxia,DONG Suzhen,WANG Huimin, et al. The molecular mechanism analysis based on the gene expression profiling of memory enhancement in NR2B transgenic mice[J].


	8. Combination of bFGF and NGF induces the differentiation of neural stem cells into neurons
	TONG Lei,TONG Xiaojie
	Biology 01 December 2010
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	Abstract:OBJECTIVE: To use the combination of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in inducing adult rat hippocampal NSCs into neurons. METHODS: The rat brain hippocampus was removed sterilely. Cell suspension was prepared and diluted when the diameter of the fourth passage of clone sphere was 200 μm by mixture of DMEM/F12 containing 2% B27, 20 μg/L epidermal growth factor (EGF) and 20 μg/L bFGF. Monoclonal cells were passaged. NSCs were divided into blank control, bFGF, NGF and bFGF+NGF groups. Immunocytochemistry for identification of NSCs was done to detect positive rate of neuron specific enolase (NSE) and the differentiation of NSCs into neurons. RESULTS: ①The monoclonal cells expressed nestin and the differentiated cells expressed NSE and glial fibrillary acidic protein. ②The proportion of NSE-positive cells in bFGF group, NGF group and bFGF+NGF group were much higher than in blank control group (P < 0.05), with the highest in bFGF+NGF group (P < 0.05). CONCLUSION: These indicate that bFGF and NGF can induce the differentiation of adult rat hippocampal NSCs into neurons.
	TO cite this article:TONG Lei,TONG Xiaojie. Combination of bFGF and NGF induces the differentiation of neural stem cells into neurons[OL].[ 1 December 2010] http://en.paper.edu.cn/en_releasepaper/content/4394441


	9. GLP-1 Protects against Aβ1-40-Induced Impairment of Hippocampal Late-Phase Long-Term Potentiation and Spatial Learning and Memory in Rats
	Wang Xiaohui ,Li Lin ,Pan Yanfang ,Chen Xiaorong ,Christian Hölscher,Qi Jinshun
	Biology 12 January 2010
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	Abstract:
	TO cite this article:Wang Xiaohui ,Li Lin ,Pan Yanfang , et al. GLP-1 Protects against Aβ1-40-Induced Impairment of Hippocampal Late-Phase Long-Term Potentiation and Spatial Learning and Memory in Rats[OL].[12 January 2010] http://en.paper.edu.cn/en_releasepaper/content/38831


	10. Histamine improves rat rota-rod and balance beam performances through H2 receptors in the cerebellar interpositus nucleus
	Yue-Ning SONG,Li Hongzhao,Zhu Jingning,Guo Chunli,Jian-Jun WANG
	Biology 09 January 2009
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	Abstract:Previous studies have revealed a direct histaminergic projection from the tuberomamillary nucleus of hypothalamus to the cerebellum and a postsynaptic excitatory effect of histamine on the cerebellar interpositus nucleus neurons via histamine H2 receptors in vitro, indicating that the histaminergic afferent inputs of cerebellar nuclei may be involved in the cerebellar function of motor control. To test this hypothesis, in this study histaminergic agents were bilaterally microinjected into the cerebellar interpositus nucleus of intact adult male rats, and their effects on motor balance and coordination of the animals performing accelerating rota-rod treadmill and balance beam tasks were observed. The results showed that microinjection of histamine into the cerebellar interpositus nucleus remarkably increased the time that animals balanced steadily on the rota-rod and markedly shortened the duration of passage through the balance beam, whereas 冏-aminobutyric acid significantly depressed motor performances of animals on the rota-rod and beam, and normal saline influenced neither. In addition, administration of selective histamine H2 receptor antagonist ranitidine considerably decreased the animalsˇ endurance time on rota-rod and noticeably increased the passing time on beam, but selective histamine H1 receptor antagonist triprolidine showed no effect. Furthermore, microinjection of histamine reversed the inhibitory effects of ranitidine on rota-rod and beam performance. These results demonstrate that histamine enhances rat motor balance and coordination through activation of histamine H2 receptors in the cerebellar interpositus nucleus and suggest that the hypothalamocerebellar histaminergic projections may play a modulatory role on the cerebellar circuitry to ensure movements to be accurately executed.
	TO cite this article:Yue-Ning SONG,Li Hongzhao,Zhu Jingning, et al. Histamine improves rat rota-rod and balance beam performances through H2 receptors in the cerebellar interpositus nucleus[OL].[ 9 January 2009] http://en.paper.edu.cn/en_releasepaper/content/27587

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