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題名 BK離子通道與海馬迴粒細胞死亡的相關性
The relationship between BK channel alternative splicing and granule cell death in the hippocampus
作者 吳君逸
Wu, Jun Yi
貢獻者 賴桂珍
Lai, Guey Jen
吳君逸
Wu, Jun Yi
關鍵詞 BK離子通道
海馬迴
齒狀回
BK
Hippocampus
Dentate gyrus
日期 2011
上傳時間 30-Oct-2012 15:22:10 (UTC+8)
摘要 海馬迴不僅在學習與記憶中扮演重要的角色，在許多神經退化性疾病中亦佔有重要的地位。海馬迴的齒迴內側區是哺乳動物大腦中成體幹細胞主要來源區域之一，其所新生的海馬迴粒細胞會往上遷移至海馬迴粒細胞層並與固有神經細胞形成功能性連結。
     過去的研究發現太少或過量的壓力荷爾蒙均會造成海馬迴粒細胞的死亡，而一定量濃度的皮質固醇對於維持海馬迴粒細胞的生存亦扮演非常重要的角色。在摘除兩側的腎上腺後，海馬迴粒細胞在幾週後會逐漸死亡且造成認知功能的缺損。本實驗即利用雙側腎上腺摘除術建立動物模式，企圖了解海馬迴粒細胞在凋亡的過程中所產生的生理層面的改變。
      壓力荷爾蒙（包含皮質固醇，在老鼠稱為corticosterone，在人類稱為cortisol）為腎上腺皮質分泌激素，已知會參與並調控BK 離子通道的選擇性剪接。BK離子通道的孔道形成α次單元由單一基因 (Slo) 負責轉錄，含有STREX外顯子的剪接變異體之α次單元藉由加速神經細胞的再極化，增強過極化電位以及促進鈉離子通道自去活化狀態中回復可造成神經細胞重複激發，而先前的研究已發現過度的激發會對神經細胞產生興奮性毒殺作用。本實驗即探討BK 鉀離子通道選擇性剪接在海馬迴粒細胞凋亡的過程中所扮演的角色。 實驗結果發現，與對照組相比，雙側腎上腺摘除的老鼠海馬迴細胞中含有STREX外顯子的剪接變異體在mRNA含量上確實有改變，而BK 鉀離子通道蛋白質含量亦有所變化。由上述結果推測，含有STREX外顯子的剪接變異體含量可能與海馬迴粒細胞的凋亡機制有關。
The hippocampus is a brain region central to learning and memory and is a key target of many neurological diseases that have dramatic cognitive consequences, including Alzheimer’s and other forms of dementia, stroke, epilepsy, and chronic stress. Hippocampal granule cells are one of the two cell pools that contain newborn neurons continuously generated from the subgranular zone in adult mammalian brains. The newborn neurons will migrate to the granule cell layer and integrate into preexisting neuron network. Previous studies have indicated that both an excessive and insufficient levels of stress hormones can lead to neuron death. Corticosterone, an adrenal stress hormone, is essential for the survival of granule cells. Bilateral removal of adrenal glands leads to extensive granule cell death over a period of several weeks and gradually causes cognitive deficits. To understand the mechanisms underlying the granule cell death in the hippocampal formation, adrenalectomy (ADX, removal of adrenal glands) was used to specifically eliminate granule cells in the hippocampus, and the subsequent physiological changes in the hippocampal neurons including dentate granule cells are investigated.
     
     Stress hormones (corticosterone in rats and cortisol in human) , secreted from the adrenal cortex regulate the alternative splicing of BK channels (big potassium, calcium-voltage activated potassium channels) in adrenal medulla. An inclusion of STREX (stress axis-regulated exon) exon in pore-forming α subunit encoded by Slo gene promotes repetitive firing by speeding action potential repolarization and augmenting the afterhyperpolarization, as well as facilitating sodium channels de-inactivation. In the present study, the role of BK channel alternative splicing in the ADX-induced granule cell death in the hippocampus was explored. The results indicate that BK channel alternative splicing was regulated by stress hormones in the hippocampus including dentate gyrus. The expression patterns of STREX variant in hippocampus were altered after granule cells death induced by ADX, whilst the expression of total slo gene was changes only in translational level. These observations suggest that the alternation in STREX abundance might be involved in the induction of dentate granule cell death.
參考文獻 1.Amaral DG, Scharfman HE, Lavenex P (2007) The dentate
      gyrus: fundamental neuroanatomical organization (dentate
      gyrus for dummies). Prog Brain Res 163:3-22.
     2.Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L (1993)
      mSlo, a complex mouse gene encoding "maxi" calcium-
      activated potassium channels. Science 261:221-224.
     3.Cameron HA, Gould E (1994) Adult neurogenesis is
      regulated by adrenal steroids in the dentate gyrus.
      Neuroscience 61:203-209.
     4.Cui J, Yang H, Lee US (2009) Molecular mechanisms of BK
      channel activation. Cell Mol Life Sci 66:852-875.
     5.De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998)
      Brain corticosteroid receptor balance in health and
      disease. Endocrine reviews 19:269-301.
     6.Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA, Wang
      L, Kotagal P, Luders HO, Shi J, Cui J, Richerson GB, Wang
      QK (2005) Calcium-sensitive potassium channelopathy in
      human epilepsy and paroxysmal movement disorder. Nat
      Genet 37:733-738.
     7.Faber ES, Sah P (2003) Calcium-activated potassium
      channels: multiple contributions to neuronal function.
      Neuroscientist 9:181-194.
     8.Gage FH (2000) Mammalian neural stem cells. Science
      287:1433-1438.
     9.Gotz J, Ittner LM (2008) Animal models of Alzheimer`s
      disease and frontotemporal dementia. Nat Rev Neurosci
      9:532-544.
     10.Gutierrez R (2003) The GABAergic phenotype of
      the "glutamatergic" granule cells of the dentate gyrus.
      Prog Neurobiol 71:337-358.
     11.Hagihara H, Toyama K, Yamasaki N, Miyakawa T (2009)
      Dissection of hippocampal dentate gyrus from adult
      mouse. J Vis Exp.
     12.Hernandez-Rabaza V, Hontecillas-Prieto L, Velazquez-
      Sanchez C, Ferragud A, Perez-Villaba A, Arcusa A, Barcia
      JA, Trejo JL, Canales JJ (2008) The hippocampal dentate
      gyrus is essential for generating contextual memories of
      fear and drug-induced reward. Neurobiol Learn Mem 90:553-
      559.
     13.Holmes MC, Yau JL, French KL, Seckl JR (1995) The effect
      of adrenalectomy on 5-hydroxytryptamine and
      corticosteroid receptor subtype messenger RNA expression
      in rat hippocampus. Neuroscience 64:327-337.
     14.Hu Z, Yuri K, Ozawa H, Lu H, Kawata M (1997) The in vivo
      time course for elimination of adrenalectomy-induced
      apoptotic profiles from the granule cell layer of the
      rat hippocampus. J Neurosci 17:3981-3989.
     15.Jaarsma D, Postema F, Korf J (1992) Time course and
      distribution of neuronal degeneration in the dentate
      gyrus of rat after adrenalectomy: a silver impregnation
      study. Hippocampus 2:143-150.
     16.Joels M (2007) Role of corticosteroid hormones in the
      dentate gyrus. Prog Brain Res 163:355-370.
     17.Joels M, Stienstra C, Karten Y (2001) Effect of
      adrenalectomy on membrane properties and synaptic
      potentials in rat dentate granule cells. J Neurophysiol
      85:699-707.
     18.Joels M, Karst H, Krugers HJ, Lucassen PJ (2007) Chronic
      stress: implications for neuronal morphology, function
      and neurogenesis. Front Neuroendocrinol 28:72-96.
     19.Joels M, Karst H, DeRijk R, de Kloet ER (2008) The
      coming out of the brain mineralocorticoid receptor.
      Trends Neurosci 31:1-7.
     20.Karst H, Joels M (2001) Calcium currents in rat dentate
      granule cells are altered after adrenalectomy. Eur J
      Neurosci 14:503-512.
     21.Kesner RP (2007) A behavioral analysis of dentate gyrus
      function. Prog Brain Res 163:567-576.
     22.Knaus HG, Schwarzer C, Koch RO, Eberhart A, Kaczorowski
      GJ, Glossmann H, Wunder F, Pongs O, Garcia ML, Sperk G
      (1996) Distribution of high-conductance Ca(2+)-activated
      K+ channels in rat brain: targeting to axons and nerve
      terminals. J Neurosci 16:955-963.
     23.Krugers HJ, van der Linden S, van Olst E, Alfarez DN,
      Maslam S, Lucassen PJ, Joels M (2007) Dissociation
      between apoptosis, neurogenesis, and synaptic
      potentiation in the dentate gyrus of adrenalectomized
      rats. Synapse 61:221-230.
     24.Kumar P, Kalonia H, Kumar A (2010) Huntington`s disease:
      pathogenesis to animal models. Pharmacol Rep 62:1-14.
     25.Lai GJ, McCobb DP (2002) Opposing actions of adrenal
      androgens and glucocorticoids on alternative splicing of
      Slo potassium channels in bovine chromaffin cells. Proc
      Natl Acad Sci U S A 99:7722-7727.
     26.Lai GJ, McCobb DP (2006) Regulation of alternative
      splicing of Slo K+ channels in adrenal and pituitary
      during the stress-hyporesponsive period of rat
      development. Endocrinology 147:3961-3967.
     27.Lee I, Kesner RP (2004) Differential contributions of
      dorsal hippocampal subregions to memory acquisition and
      retrieval in contextual fear-conditioning. Hippocampus
      14:301-310.
     28.Lees AJ, Hardy J, Revesz T (2009) Parkinson`s disease.
      Lancet 373:2055-2066.
     29.Lovell PV, McCobb DP (2001) Pituitary control of BK
      potassium channel function and intrinsic firing
      properties of adrenal chromaffin cells. J Neurosci
      21:3429-3442.
     30.Lu R, Alioua A, Kumar Y, Eghbali M, Stefani E, Toro L
      (2006) MaxiK channel partners: physiological impact. J
      Physiol 570:65-72.
     31.Maclennan KM, Zheng Y, Sheard PW, Williams SM,
      Darlington CL, Smith PF (2003) Adrenalectomy-induced
      cell death in the dentate gyrus: further
      characterisation using TUNEL and effects of the Ginkgo
      biloba extract, EGb 761, and ginkgolide B. Hippocampus
      13:212-225.
     32.Mahmoud SF, Bezzerides AL, Riba R, Lai GJ, Lovell PV,
      Hara Y, McCobb DP (2002) Accurate quantitative RT-PCR
      for relative expression of Slo splice variants. J
      Neurosci Methods 115:189-198.
     33.McNeill TH, Masters JN, Finch CE (1991) Effect of
      chronic adrenalectomy on neuron loss and distribution of
      sulfated glycoprotein-2 in the dentate gyrus of
      prepubertal rats. Exp Neurol 111:140-144.
     34.Pacheco Otalora LF, Hernandez EF, Arshadmansab MF,
      Francisco S, Willis M, Ermolinsky B, Zarei M, Knaus HG,
      Garrido-Sanabria ER (2008) Down-regulation of BK channel
      expression in the pilocarpine model of temporal lobe
      epilepsy. Brain Res 1200:116-131.
     35.Paskitti ME, McCreary BJ, Herman JP (2000) Stress
      regulation of adrenocorticosteroid receptor gene
      transcription and mRNA expression in rat hippocampus:
      time-course analysis. Brain Res Mol Brain Res 80:142-152.
     36.Rolls ET, Kesner RP (2006) A computational theory of
      hippocampal function, and empirical tests of the theory.
      Prog Neurobiol 79:1-48.
     37.Roy EJ, Lynn DM, Bemm CW (1990) Individual variations in
      hippocampal dentate degeneration following
      adrenalectomy. Behavioral and neural biology 54:330-336.
     38.Schreiber M, Salkoff L (1997) A novel calcium-sensing
      domain in the BK channel. Biophysical journal 73:1355-
      1363.
     39.Shipston MJ (2001) Alternative splicing of potassium
      channels: a dynamic switch of cellular excitability.
      Trends in cell biology 11:353-358.
     40.Sloviter RS, Sollas AL, Dean E, Neubort S (1993)
      Adrenalectomy-induced granule cell degeneration in the
      rat hippocampal dentate gyrus: characterization of an in
      vivo model of controlled neuronal death. J Comp Neurol
      330:324-336.
     41.Sloviter RS, Valiquette G, Abrams GM, Ronk EC, Sollas
      AL, Paul LA, Neubort S (1989) Selective loss of
      hippocampal granule cells in the mature rat brain after
      adrenalectomy. Science 243:535-538.
     42.Spanswick SC, Lehmann H, Sutherland RJ (2011a) A novel
      animal model of hippocampal cognitive deficits, slow
      neurodegeneration, and neuroregeneration. Journal of
      biomedicine & biotechnology 2011:527201.
     43.Spanswick SC, Epp JR, Sutherland RJ (2011b) Time-course
      of hippocampal granule cell degeneration and changes in
      adult neurogenesis after adrenalectomy in rats.
      Neuroscience 190:166-176.
     44.Stienstra CM, Joels M (2000) Effect of corticosteroid
      treatment in vitro on adrenalectomy-induced impairment
      of synaptic transmission in the rat dentate gyrus. J
      Neuroendocrinol 12:199-205.
     45.Stienstra CM, Van Der Graaf F, Bosma A, Karten YJ, Hesen
      W, Joels M (1998) Synaptic transmission in the rat
      dentate gyrus after adrenalectomy. Neuroscience 85:1061-
      1071.
     46.Vreugdenhil E, de Kloet ER, Schaaf M, Datson NA (2001)
      Genetic dissection of corticosterone receptor function
      in the rat hippocampus. Eur Neuropsychopharmacol 11:423-
      430.
     47.Xavier GF, Costa VC (2009) Dentate gyrus and spatial
      behaviour. Prog Neuropsychopharmacol Biol Psychiatry
      33:762-773.
     48.Xie J, McCobb DP (1998) Control of alternative splicing
      of potassium channels by stress hormones. Science
      280:443-446.
     49.Yu JY, Upadhyaya AB, Atkinson NS (2006) Tissue-specific
      alternative splicing of BK channel transcripts in
      Drosophila. Genes Brain Behav 5:329-339.
     50.Zarei MM, Zhu N, Alioua A, Eghbali M, Stefani E, Toro L
      (2001) A novel MaxiK splice variant exhibits dominant-
      negative properties for surface expression. J Biol Chem
      276:16232-16239.
     51.Zhao C, Deng W, Gage FH (2008) Mechanisms and functional
      implications of adult neurogenesis. Cell 132:645-660.
描述 碩士
國立政治大學
神經科學研究所
97754001
100
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0097754001
資料類型 thesis
dc.contributor.advisor 賴桂珍zh_TW
dc.contributor.advisor Lai, Guey Jenen_US
dc.contributor.author (Authors) 吳君逸zh_TW
dc.contributor.author (Authors) Wu, Jun Yien_US
dc.creator (作者) 吳君逸zh_TW
dc.creator (作者) Wu, Jun Yien_US
dc.date (日期) 2011en_US
dc.date.accessioned 30-Oct-2012 15:22:10 (UTC+8)-
dc.date.available 30-Oct-2012 15:22:10 (UTC+8)-
dc.date.issued (上傳時間) 30-Oct-2012 15:22:10 (UTC+8)-
dc.identifier (Other Identifiers) G0097754001en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/55036-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 97754001zh_TW
dc.description (描述) 100zh_TW
dc.description.abstract (摘要) 海馬迴不僅在學習與記憶中扮演重要的角色，在許多神經退化性疾病中亦佔有重要的地位。海馬迴的齒迴內側區是哺乳動物大腦中成體幹細胞主要來源區域之一，其所新生的海馬迴粒細胞會往上遷移至海馬迴粒細胞層並與固有神經細胞形成功能性連結。
     過去的研究發現太少或過量的壓力荷爾蒙均會造成海馬迴粒細胞的死亡，而一定量濃度的皮質固醇對於維持海馬迴粒細胞的生存亦扮演非常重要的角色。在摘除兩側的腎上腺後，海馬迴粒細胞在幾週後會逐漸死亡且造成認知功能的缺損。本實驗即利用雙側腎上腺摘除術建立動物模式，企圖了解海馬迴粒細胞在凋亡的過程中所產生的生理層面的改變。
      壓力荷爾蒙（包含皮質固醇，在老鼠稱為corticosterone，在人類稱為cortisol）為腎上腺皮質分泌激素，已知會參與並調控BK 離子通道的選擇性剪接。BK離子通道的孔道形成α次單元由單一基因 (Slo) 負責轉錄，含有STREX外顯子的剪接變異體之α次單元藉由加速神經細胞的再極化，增強過極化電位以及促進鈉離子通道自去活化狀態中回復可造成神經細胞重複激發，而先前的研究已發現過度的激發會對神經細胞產生興奮性毒殺作用。本實驗即探討BK 鉀離子通道選擇性剪接在海馬迴粒細胞凋亡的過程中所扮演的角色。 實驗結果發現，與對照組相比，雙側腎上腺摘除的老鼠海馬迴細胞中含有STREX外顯子的剪接變異體在mRNA含量上確實有改變，而BK 鉀離子通道蛋白質含量亦有所變化。由上述結果推測，含有STREX外顯子的剪接變異體含量可能與海馬迴粒細胞的凋亡機制有關。		zh_TW
dc.description.abstract (摘要) The hippocampus is a brain region central to learning and memory and is a key target of many neurological diseases that have dramatic cognitive consequences, including Alzheimer’s and other forms of dementia, stroke, epilepsy, and chronic stress. Hippocampal granule cells are one of the two cell pools that contain newborn neurons continuously generated from the subgranular zone in adult mammalian brains. The newborn neurons will migrate to the granule cell layer and integrate into preexisting neuron network. Previous studies have indicated that both an excessive and insufficient levels of stress hormones can lead to neuron death. Corticosterone, an adrenal stress hormone, is essential for the survival of granule cells. Bilateral removal of adrenal glands leads to extensive granule cell death over a period of several weeks and gradually causes cognitive deficits. To understand the mechanisms underlying the granule cell death in the hippocampal formation, adrenalectomy (ADX, removal of adrenal glands) was used to specifically eliminate granule cells in the hippocampus, and the subsequent physiological changes in the hippocampal neurons including dentate granule cells are investigated.
     
     Stress hormones (corticosterone in rats and cortisol in human) , secreted from the adrenal cortex regulate the alternative splicing of BK channels (big potassium, calcium-voltage activated potassium channels) in adrenal medulla. An inclusion of STREX (stress axis-regulated exon) exon in pore-forming α subunit encoded by Slo gene promotes repetitive firing by speeding action potential repolarization and augmenting the afterhyperpolarization, as well as facilitating sodium channels de-inactivation. In the present study, the role of BK channel alternative splicing in the ADX-induced granule cell death in the hippocampus was explored. The results indicate that BK channel alternative splicing was regulated by stress hormones in the hippocampus including dentate gyrus. The expression patterns of STREX variant in hippocampus were altered after granule cells death induced by ADX, whilst the expression of total slo gene was changes only in translational level. These observations suggest that the alternation in STREX abundance might be involved in the induction of dentate granule cell death.		en_US
dc.description.tableofcontents 中文摘要...I
     Abstract...II
     Table of contents...IV
     Figures...VI
     Abbreviations...VII
     1. Introduction...1
     1.1 The dentate gyrus...1
     1.2 Dentate granule cells...1
     1.3 Corticosterone and dentate granule cells...2
     1.4 Corticosterone receptors in the brain...3
     1.5 The mechanisms of adrenalectomy-induced dentate
      granule cell death...4
     1.6 Big conductance voltage-sensitive and Ca2+-activated
      potassium channel in the brain...5
     1.7 BK channel alternative splicing is regulated by
      corticosterone...7
     1.8 Hypothesis in this study...7
     2. Materials and Methods...9
     2.1 Animals and Surgery...9
     2.2 Samples collection...11
     2.3 Total RNA extraction and RT-PCR...12
     2.3.1 STREX/ZERO splice variants amplification...12
     2.3.2 Total Slo gene transcripts amplification...14
     2.4 Sample preparation and immunohistochemistry...15
     2.5 Primary cell culture and immunocytochemistry...18
     2.6 ELISA...20
     2.7 Data analysis... 21
     3. Results...22
     3.1 Attenuated body-weight gain and low plasma CORT
      levels were observed after ADX...22
     3.2 Quantitative Measurement of the Relative Abundance of
      STREX and ZERO Variants...26
     3.3 Relative abundance of STREX splice variant and total
      Slo gene transcripts in left hippocampi was not
      changed in prolonged ADX rats...28
     3.4 The alternation of STREX splice variant and total Slo
      transcripts was different in DG and left hippocampi
      after ADX...30
     3.5 The expression of BK channel α subunit protein was
      increased after ADX...33
     4. Discussion...36
     5. Conclusion…40
     6. References…41		zh_TW
dc.language.iso en_US-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0097754001en_US
dc.subject (關鍵詞) BK離子通道zh_TW
dc.subject (關鍵詞) 海馬迴zh_TW
dc.subject (關鍵詞) 齒狀回zh_TW
dc.subject (關鍵詞) BKen_US
dc.subject (關鍵詞) Hippocampusen_US
dc.subject (關鍵詞) Dentate gyrusen_US
dc.title (題名) BK離子通道與海馬迴粒細胞死亡的相關性zh_TW
dc.title (題名) The relationship between BK channel alternative splicing and granule cell death in the hippocampusen_US
dc.type (資料類型) thesisen
dc.relation.reference (參考文獻) 1.Amaral DG, Scharfman HE, Lavenex P (2007) The dentate
      gyrus: fundamental neuroanatomical organization (dentate
      gyrus for dummies). Prog Brain Res 163:3-22.
     2.Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L (1993)
      mSlo, a complex mouse gene encoding "maxi" calcium-
      activated potassium channels. Science 261:221-224.
     3.Cameron HA, Gould E (1994) Adult neurogenesis is
      regulated by adrenal steroids in the dentate gyrus.
      Neuroscience 61:203-209.
     4.Cui J, Yang H, Lee US (2009) Molecular mechanisms of BK
      channel activation. Cell Mol Life Sci 66:852-875.
     5.De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998)
      Brain corticosteroid receptor balance in health and
      disease. Endocrine reviews 19:269-301.
     6.Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA, Wang
      L, Kotagal P, Luders HO, Shi J, Cui J, Richerson GB, Wang
      QK (2005) Calcium-sensitive potassium channelopathy in
      human epilepsy and paroxysmal movement disorder. Nat
      Genet 37:733-738.
     7.Faber ES, Sah P (2003) Calcium-activated potassium
      channels: multiple contributions to neuronal function.
      Neuroscientist 9:181-194.
     8.Gage FH (2000) Mammalian neural stem cells. Science
      287:1433-1438.
     9.Gotz J, Ittner LM (2008) Animal models of Alzheimer`s
      disease and frontotemporal dementia. Nat Rev Neurosci
      9:532-544.
     10.Gutierrez R (2003) The GABAergic phenotype of
      the "glutamatergic" granule cells of the dentate gyrus.
      Prog Neurobiol 71:337-358.
     11.Hagihara H, Toyama K, Yamasaki N, Miyakawa T (2009)
      Dissection of hippocampal dentate gyrus from adult
      mouse. J Vis Exp.
     12.Hernandez-Rabaza V, Hontecillas-Prieto L, Velazquez-
      Sanchez C, Ferragud A, Perez-Villaba A, Arcusa A, Barcia
      JA, Trejo JL, Canales JJ (2008) The hippocampal dentate
      gyrus is essential for generating contextual memories of
      fear and drug-induced reward. Neurobiol Learn Mem 90:553-
      559.
     13.Holmes MC, Yau JL, French KL, Seckl JR (1995) The effect
      of adrenalectomy on 5-hydroxytryptamine and
      corticosteroid receptor subtype messenger RNA expression
      in rat hippocampus. Neuroscience 64:327-337.
     14.Hu Z, Yuri K, Ozawa H, Lu H, Kawata M (1997) The in vivo
      time course for elimination of adrenalectomy-induced
      apoptotic profiles from the granule cell layer of the
      rat hippocampus. J Neurosci 17:3981-3989.
     15.Jaarsma D, Postema F, Korf J (1992) Time course and
      distribution of neuronal degeneration in the dentate
      gyrus of rat after adrenalectomy: a silver impregnation
      study. Hippocampus 2:143-150.
     16.Joels M (2007) Role of corticosteroid hormones in the
      dentate gyrus. Prog Brain Res 163:355-370.
     17.Joels M, Stienstra C, Karten Y (2001) Effect of
      adrenalectomy on membrane properties and synaptic
      potentials in rat dentate granule cells. J Neurophysiol
      85:699-707.
     18.Joels M, Karst H, Krugers HJ, Lucassen PJ (2007) Chronic
      stress: implications for neuronal morphology, function
      and neurogenesis. Front Neuroendocrinol 28:72-96.
     19.Joels M, Karst H, DeRijk R, de Kloet ER (2008) The
      coming out of the brain mineralocorticoid receptor.
      Trends Neurosci 31:1-7.
     20.Karst H, Joels M (2001) Calcium currents in rat dentate
      granule cells are altered after adrenalectomy. Eur J
      Neurosci 14:503-512.
     21.Kesner RP (2007) A behavioral analysis of dentate gyrus
      function. Prog Brain Res 163:567-576.
     22.Knaus HG, Schwarzer C, Koch RO, Eberhart A, Kaczorowski
      GJ, Glossmann H, Wunder F, Pongs O, Garcia ML, Sperk G
      (1996) Distribution of high-conductance Ca(2+)-activated
      K+ channels in rat brain: targeting to axons and nerve
      terminals. J Neurosci 16:955-963.
     23.Krugers HJ, van der Linden S, van Olst E, Alfarez DN,
      Maslam S, Lucassen PJ, Joels M (2007) Dissociation
      between apoptosis, neurogenesis, and synaptic
      potentiation in the dentate gyrus of adrenalectomized
      rats. Synapse 61:221-230.
     24.Kumar P, Kalonia H, Kumar A (2010) Huntington`s disease:
      pathogenesis to animal models. Pharmacol Rep 62:1-14.
     25.Lai GJ, McCobb DP (2002) Opposing actions of adrenal
      androgens and glucocorticoids on alternative splicing of
      Slo potassium channels in bovine chromaffin cells. Proc
      Natl Acad Sci U S A 99:7722-7727.
     26.Lai GJ, McCobb DP (2006) Regulation of alternative
      splicing of Slo K+ channels in adrenal and pituitary
      during the stress-hyporesponsive period of rat
      development. Endocrinology 147:3961-3967.
     27.Lee I, Kesner RP (2004) Differential contributions of
      dorsal hippocampal subregions to memory acquisition and
      retrieval in contextual fear-conditioning. Hippocampus
      14:301-310.
     28.Lees AJ, Hardy J, Revesz T (2009) Parkinson`s disease.
      Lancet 373:2055-2066.
     29.Lovell PV, McCobb DP (2001) Pituitary control of BK
      potassium channel function and intrinsic firing
      properties of adrenal chromaffin cells. J Neurosci
      21:3429-3442.
     30.Lu R, Alioua A, Kumar Y, Eghbali M, Stefani E, Toro L
      (2006) MaxiK channel partners: physiological impact. J
      Physiol 570:65-72.
     31.Maclennan KM, Zheng Y, Sheard PW, Williams SM,
      Darlington CL, Smith PF (2003) Adrenalectomy-induced
      cell death in the dentate gyrus: further
      characterisation using TUNEL and effects of the Ginkgo
      biloba extract, EGb 761, and ginkgolide B. Hippocampus
      13:212-225.
     32.Mahmoud SF, Bezzerides AL, Riba R, Lai GJ, Lovell PV,
      Hara Y, McCobb DP (2002) Accurate quantitative RT-PCR
      for relative expression of Slo splice variants. J
      Neurosci Methods 115:189-198.
     33.McNeill TH, Masters JN, Finch CE (1991) Effect of
      chronic adrenalectomy on neuron loss and distribution of
      sulfated glycoprotein-2 in the dentate gyrus of
      prepubertal rats. Exp Neurol 111:140-144.
     34.Pacheco Otalora LF, Hernandez EF, Arshadmansab MF,
      Francisco S, Willis M, Ermolinsky B, Zarei M, Knaus HG,
      Garrido-Sanabria ER (2008) Down-regulation of BK channel
      expression in the pilocarpine model of temporal lobe
      epilepsy. Brain Res 1200:116-131.
     35.Paskitti ME, McCreary BJ, Herman JP (2000) Stress
      regulation of adrenocorticosteroid receptor gene
      transcription and mRNA expression in rat hippocampus:
      time-course analysis. Brain Res Mol Brain Res 80:142-152.
     36.Rolls ET, Kesner RP (2006) A computational theory of
      hippocampal function, and empirical tests of the theory.
      Prog Neurobiol 79:1-48.
     37.Roy EJ, Lynn DM, Bemm CW (1990) Individual variations in
      hippocampal dentate degeneration following
      adrenalectomy. Behavioral and neural biology 54:330-336.
     38.Schreiber M, Salkoff L (1997) A novel calcium-sensing
      domain in the BK channel. Biophysical journal 73:1355-
      1363.
     39.Shipston MJ (2001) Alternative splicing of potassium
      channels: a dynamic switch of cellular excitability.
      Trends in cell biology 11:353-358.
     40.Sloviter RS, Sollas AL, Dean E, Neubort S (1993)
      Adrenalectomy-induced granule cell degeneration in the
      rat hippocampal dentate gyrus: characterization of an in
      vivo model of controlled neuronal death. J Comp Neurol
      330:324-336.
     41.Sloviter RS, Valiquette G, Abrams GM, Ronk EC, Sollas
      AL, Paul LA, Neubort S (1989) Selective loss of
      hippocampal granule cells in the mature rat brain after
      adrenalectomy. Science 243:535-538.
     42.Spanswick SC, Lehmann H, Sutherland RJ (2011a) A novel
      animal model of hippocampal cognitive deficits, slow
      neurodegeneration, and neuroregeneration. Journal of
      biomedicine & biotechnology 2011:527201.
     43.Spanswick SC, Epp JR, Sutherland RJ (2011b) Time-course
      of hippocampal granule cell degeneration and changes in
      adult neurogenesis after adrenalectomy in rats.
      Neuroscience 190:166-176.
     44.Stienstra CM, Joels M (2000) Effect of corticosteroid
      treatment in vitro on adrenalectomy-induced impairment
      of synaptic transmission in the rat dentate gyrus. J
      Neuroendocrinol 12:199-205.
     45.Stienstra CM, Van Der Graaf F, Bosma A, Karten YJ, Hesen
      W, Joels M (1998) Synaptic transmission in the rat
      dentate gyrus after adrenalectomy. Neuroscience 85:1061-
      1071.
     46.Vreugdenhil E, de Kloet ER, Schaaf M, Datson NA (2001)
      Genetic dissection of corticosterone receptor function
      in the rat hippocampus. Eur Neuropsychopharmacol 11:423-
      430.
     47.Xavier GF, Costa VC (2009) Dentate gyrus and spatial
      behaviour. Prog Neuropsychopharmacol Biol Psychiatry
      33:762-773.
     48.Xie J, McCobb DP (1998) Control of alternative splicing
      of potassium channels by stress hormones. Science
      280:443-446.
     49.Yu JY, Upadhyaya AB, Atkinson NS (2006) Tissue-specific
      alternative splicing of BK channel transcripts in
      Drosophila. Genes Brain Behav 5:329-339.
     50.Zarei MM, Zhu N, Alioua A, Eghbali M, Stefani E, Toro L
      (2001) A novel MaxiK splice variant exhibits dominant-
      negative properties for surface expression. J Biol Chem
      276:16232-16239.
     51.Zhao C, Deng W, Gage FH (2008) Mechanisms and functional
      implications of adult neurogenesis. Cell 132:645-660.		zh_TW