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Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

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Neural Regeneration Research 2014年第22期9卷 1985-1994页

作者： Yifan He Jihong Zhu Fang Huang Liu Qin Wenguo Fan Hongwen He Guanghua School of Stomatology Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Stomatology Huaihe Hospital Henan University

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged （4-month-old） or elderly （7-month-old） senescence-accelerated mouse prone 8 （SAMP8） mice. When the middle-aged mice reached 8 months （middle-aged group 1） or 11 months （middle-aged group 2）, and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus （Nissl staining and acetylcholinesterase histochemistry） and basal forebrain （choline acetyltrans-ferase immunohistochemistry）. In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these p

关键词： nerve regeneration Alzheimer＇ s disease trigeminal nerve learning memory hippocampal CA1 hippocampal CA3 dentate gyrus basal forebrain medial septal nucleus vertical limb of the diagonal band cholinergic neurons cholinergic fibers pyramidal cells NSFC grants neural regeneration

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Neuroprotective effects of roasted licorice,not raw form,on neuronal injury in gerbil hippocampus after transient forebrain ischemia

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Acta Pharmacologica Sinica 2006年第8期27卷 959-965页

作者： In-koo HWANG Soon-sung LIM Kyu-hyun CHOI Ki-yeon YOO Hyun-kyung SHIN Eun-ji KIM Jung-han YOONPARK Tae-cheon KANG Young-sup KIM Dae-young KWON Dong-woo KIM Won-kook MOON Moo-ho WON Korea Central Research Institute.Natural F&P Co Ltd Chunchon 200-160Korea Silver Biotechnology Research Center Korea Silver Biotechnology Research Center Department of Food Science and Nutrition Hallym UniversityChunchon 200-702Korea Medical Science Division Korea Research Institute of Chemical TechnologyYuseong.Daejeon 305-343Korea Korea Central Research Institute.Natural F&P Co Ltd Chunchon 200-160Korea Korea Silver Biotechnology Research Center

Aim:To observe neuroprotective effects of raw and roasted licorice against hy-poxia and ischemic damage.Methods:When elucidating the protective effects ofraw and roasted licorice,we analyzed the lactate dehydrogenase (LDH) releaseusing PC12 cells after hypoxia in an in vitro study and after transient forebrainischemia in an in vivo study on Mongolian gerbils.Results:Raw and roastedlicorice significantly reduced LDH release from PC12 cells exposed to an hypoxicchamber for 1h.In the roasted licorice-treated group,the decrease of LDH releasewas more pronounced compared to that of the raw licorice-treated group.Inroasted licorice-treated animals,approximately 66%-71% of CA1 pyramidal cellsin the ischemic hippocampus were stained with cresyl violet compared to thecontrol group.However,in the raw licorice-treated animals,no significantneuroprotection against ischemic damage was shown.In addition,ischemic ani-mals in roasted licorice-treated group maintained the Cu,Zn-superoxide dismutase(SOD1) activity and protein levels compared to the control group,while in rawlicorice-treated group SOD1 activity and protein levels were reduced significantly.High pressure liquid chromatography analysis showed that non-polar compoundscontaining glycyrrhizin-degraded products,such as glycyrrhetinic acid (GA) andglycyrrhetinic acid monoglucuronide (GM),were increased in roasted licorice.Conclusion:Roasted licorice had neuroprotective effects against ischemic dam-age by maintaining the SOD1 levels.In addition,the difference in protectiveability between raw and roasted licorice may be associated with non-polarcompounds,such as GA and GM.

关键词： transient ischemic attack roasted licorice raw licorice neurons PC12 cells hippocampus pyramidal cells Gerbillinae superoxide dismutase

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Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia

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Neural Regeneration Research 2016年第8期11卷 1254-1259页

作者： Dae Young Yoo Kwon Young Lee Joon Ha Park Hyo Young Jung Jong Whi Kim Yeo Sung Yoon Moo-Ho Won Jung Hoon Choi In Koo Hwang Department of Anatomy and Cell Biology College of Veterinary Medicineand Research Institute for Veterinary ScienceSeoul National University Department of Anatomy College of Veterinary Medicine and Institute of Veterinary ScienceKangwon National University Department of Neurobiology School of MedicineKangwon National University

Recent evidence exists that glucose transporter 3（GLUT3） plays an important role in the energy metabolism in the brain.Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and m RNA levels rather than tissue levels.In the present study,we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia.In the sham-operated group,GLUT3 immunoreactivity in the hippocampal CA1 region was weak,in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia,and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia,with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia.In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein（GFAP）,we observed strong GLUT3 immunoreactivity in the astrocytes.GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion.In a double immunofluorescence study using GLUT3 and doublecortin（DCX）,we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia.GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus.These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus.

关键词： nerve regeneration transient forebrain ischemia glucose transporter 3 pyramidal cells astrocytes neuroblasts neural regeneration

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Effects of Urtica dioica extract on CA3 hippocampal pyramidal cell loss in young diabetic rats

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Neural Regeneration Research 2010年第12期5卷 901-905页

作者： Seyyed Amirhossein Fazeli Anneh Mohammad Gharravi Soraya Ghafari Mehrdad Jahanshahi Mohammad Jafar Golalipour Department of Embryology and Histology Gorgan University of Medical Sciences Gorgan Iran Department of Anatomy Gorgan University of Medical Sciences Gorgan Iran

BACKGROUND： Urtica dioica extract has been shown to play a protective role in the neurodegeneration associated with diabetes mellitus. OBJECTIVE： To verify the neuroprotective efficacy of nettle extract on pyramidal cell density in the CA3 hippocampal subfield following administration of Urtica dioica extract to young diabetic rats. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiological study was performed at the Department of Histology and Embryology at the Gorgan University of Medical Sciences in Iran from 2006 to 2007. MATERIALS： Urtica dioica leaves were collected from a cultivated plant in the suburb of Gorgan （northem Iran） and taxonomically identified by the Department of Pharmacognosy, Mazandaran University of Medical Sciences. METHODS： A total of 20 male, albino, Wistar rats, aged 6-7 postnatal weeks, were randomly assigned to four groups： normal control, diabetic model, preventive, and treatment, with five rats in each group. Diabetes was induced by intraperitoneal injection of streptozotocin （80 mg/kg） in the diabetic and treatment groups. Rats from the preventive group received a hydroalcoholic extract of Urtica dioica （100 mg/kg per day） during the first 5 days, and then streptozotocin （80 mg/kg） was administered on day 6. One week following the streptozotocin injection, rats in the treatment group were intraperitoneally administered hydroalcoholic extract of Urtica dioica （100 mg/kg per day） for 4 weeks. MAIN OUTCOME MEASURES： Following administration of Urtica dioica extract, the dorsal hippocampal formation of the right cerebral hemispheres was stained with cresyl violet. Area densities of CA3 pyramidal cells were measured. RESULTS： The diabetic, preventive, and treatment groups exhibited reduced cell densities compared with the control group （P 〈 0.05）. Moreover, densities of CA3 pyramidal cells in the treatment group were significantly reduced compared with the diabetic model group （P 〈 0.05）. CONCLUSION： The Urtica dioica extract exhibited no significant neuroprotectJve benefits in

关键词： Urtica dioica hippocampus pyramidal cells diabetes neuroprotective efficacy

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Inhibition of evoked glutamate release by neurosteroid allopregnanolone via inhibition of L type calcium channels in rat medial prefrontal cortex

Inhibition of evoked glutamate release by neurosteroid allop...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Ping ZHENG,Ai-Qun HU,Ze-Min WANG,Dan-Mei LAN.Ying-Mei FU,Yan-Hua ZHU,Yi DONG State Key Laboratory of Medical Neurobiology,Fudan University Shanghai Medical College,Shanghai 200032, China

＜正＞Allopregnanolone is one of the most important neurosteroids in the brain.We studied the effect and mechanism of allopregnanolone on spontaneous and evoked glutamate release in the medial prefrontal cortex using electrophysiological and biochemical methods combined with pharmacological approaches.The results showed that allopregnanolone had no effects on the frequency of miniature excitatory postsynaptic current（mEPSCs）,but inhibited the depolarizing agent veratridine-evoked increase in the frequency of spontaneous excitatory postsynaptic currents（sEPSCs） and inhibited the first of the two responses evoked by a pair of electrical pulses more effectively than the second,resulting in increased paired-pulse facilitation（PPF） and thus suggesting a presynaptic inhibitory effect on electrical pulse-evoked glutamate release.A similar effect was also obtained for the effect of allopregnanolone on protein kinase A（PKA） activation, an upstream event of presynaptic glutamate release.Interestingly,allopregnanolone had none of these effects in the striatum.In the study of the upstream mechanism of the PKA inhibition by allopregnanolone,we found that allopregnanolone inhibited extracellular calcium influx-evoked PKA activation,but had no effects on intracellular calcium store releaseevoked PKA activation;L-type calcium channel antagonists,but not N- and P/Q-type calcium channel antagonist,blocked the effect of allopregnanolone;allopregnanolone inhibited L-type calcium channel agonist-evoked increase in the PKA activity,intrasynaptosomal calcium concentration and frequency of sEPSCs.These results suggest that allopregnanolone inhibits evoked glutamate release via the inhibition of L-type calcium channels in the medial prefrontal cortex,but does not in the striatum.

关键词： medial prefrontal cortex pyramidal cells excitatory postsynaptic currents neurosteroid allopregnanolone

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Axonal potassium current and its modulation by neuromodulators

Axonal potassium current and its modulation by neuromodulato...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Yang JING,You-Sheng SHU~* Laboratory of neural network function,Institute of Neuroscience,Chinese Academy of Sciences,Shanghai,200031, China

Potassium(K) currents are fundamental determinants of the neuronal membrane excitability,and thereby affect the activities of neural networks.Using whole-cell recording at the cut end of the axon in both pyramidal cells and interneurons of prefrontal cortex,we studied the properties and functions of axonal K currents.A slowly inactivating K current(D-current) is found dominantly at the axon of both interneuron and pyramidal cell.Blocking this slowly inactivat- ing current byα-DTX produced repetitive firing in response to axonal current injection.These results suggested that the the axonal D-current may play an important role in controlling axonal electrical properties and the firing patterns of these neurons.As the K channels are subjected to modulation through protein phosphorylation,we examined the modulation of axonal K currents by various potential modulators that could alter the activity of intracellular kinases.We examined the effect of NE,5-HT,DA and the related receptor agonists on the amplitude and gating properties of axonal K currents.We found that some of these modulators may regulate the axonal K channels via PKA signaling pathway.Activation of adenylate cyclase by forskolin significantly suppressed the axonal voltage-gated K current.These results indicated that neuromodulators may change the neuronal excitability and firing patterns via their modulatory effect on axonal K channels.

关键词： potassium current interneuron pyramidal cells neuromodulators

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Primary observation on in vivo firing patterns of neurons in mice medial prefrontal cortex

Primary observation on in vivo firing patterns of neurons in...

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中国神经科学学会第十二届全国学术会议

作者： Yanting Yao Longnian Lin Key Laboratory of Brain Functional Genomics （Ministry of Education） Institute of Brain Functional Genomics East China Normal University

In neocortex, varieties of GABAergic interneurons regulate the activity of excitatory pyramidal cells and other inhibitory interneurons. To investigate how the cortical networks process information, it is necessary to find out the in vivo firing patterns of different subtypes of cortical neurons during information processing. Here we recorded neurons in medial prefrontal cortex（m PFC） in freely behaving mice with multichannel recording techniques, and analyzed the relation of their firing pattern with animal behavior and local field potential. Results showed that the majority of the recorded pyramidal cells increased their average firing rates when mice were carrying out cognition related tasks, such as exploring new environments, performing social behavior, or responding to air puff stimulations, indicating that they were involved in information encoding during these tasks. Meanwhile, though less in quantity compared with pyramidal cells, the recorded m PFC interneurons maintained high baseline firing rates. According to the relation of their firing rates with behavioral states, these m PFC interneurons could be classified into two major subtypes. For one subtype of interneurons, firing patterns changed with animal behavior. Generally, their mean firing rates during active exploration was higher than those during SWS sleep. Analyzation of inter-spike intervals（ISI） and power spectral densities（PSD） revealed different characteristics during these two states as well. While the other subtype of interneurons exhibited similar activity characteristics across behavioral states. No significant difference in ISI and PSD was observed between states. Our findings suggest that pyramidal cells and interneurons get involved in mPFC information processing via different firing patterns.

关键词： medial prefrontal cortex pyramidal cells interneurons in vivo firing patterns

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