臺灣博碩士論文加值系統

本論文主要探討飲食中缺乏n-3多元不飽和脂肪酸對大鼠腦區二十二碳六烯酸含量及經由壓力誘發之神經內分泌路徑─下視丘-腦下垂體-腎上腺路徑反應的影響。
利用Sprague-Dawley雄性大鼠，在離乳之後給予n-3多元不飽和脂肪酸缺乏或正常的飼料7週。觀察其腦區二十二碳六烯酸含量的變化，並以行為實驗檢驗兩組大鼠在焦慮及憂鬱相關行為的表現。透過給予大鼠束縛壓力1小時後，檢測其下視丘-腦下垂體-腎上腺路徑的反應。大鼠於犧牲後分析各腦區DHA含量、血清中糖皮質類固醇的含量、糖皮質類固醇受體蛋白及brain-derived neurotrophic factor (BDNF)蛋白在海馬及下視丘的表現。實驗結果發現在離乳後攝取缺乏n-3多元不飽和脂肪酸飼料的大鼠，不論在海馬、下視丘、前額葉皮質、杏仁核、腦幹及肝臟，二十二碳六烯酸的含量均較正常組顯著地降低。然而在焦慮或憂鬱相關行為的檢測上兩組並無差異。在給予束縛壓力後，血中糖皮質類固醇的濃度在攝取n-3多元不飽和脂肪酸缺乏飼料的組別明顯較高。但在海馬及下視丘的糖皮質類固醇受體蛋白表現量並無差異，而BDNF蛋白於海馬的表現量在壓力後，缺乏n-3多元不飽和脂肪酸的組別會較正常組別下降。綜合以上，本論文主要發現雄性大鼠離乳後，攝取缺乏n-3多元不飽和脂肪酸飼料7周會造成各腦區二十二碳六烯酸含量顯著下降，及增加由壓力誘發的糖皮質固醇分泌。

Most previous studies have focused on rat docosahexaenoic acid (22:6n-3, DHA) deficiency created during brain development via maternal n-3 fatty acid-deficient diet from pregnancy and lactation on adult anxiety and depression behaviors. It has been suggested the anxiety and depression is associated with hypothalamic-pituitary-adrenal axis (HPA axis) responses. The aim of this study was to evaluate whether brain DHA deficiency during post-weaning period would enhance restrain-induced HPA axis responses and anxiety or depression-like behavior in adult male rats. After weaning at postnatal day 21, male rats fed an n-3 fatty acid-deficient or an n-3 fatty acid-adequate diet till sacrificed at postnatal day 70. The DHA levels were significant decreased in hypothalamus and hippocampus and other brain regions in rats fed with n-3 fatty acid-deficient diet compared to the rats fed with n-3 fatty acid-adequate diet during post-weaning period for 7 weeks. The anxiety-like behavior in the elevated plus-maze test and depressive-like behavior in the forced swim test were no difference between groups. The restraint-induced rectal temperature was increased during the restraint, but no difference between groups. The serum corticosterone was significant increased right after restraint in rats fed an n-3 fatty acid-deficient diet. The GR expression in hippocampus and hypothalamus were no difference between groups. The BDNF was significant decreased in hippocampus after restraint in rats fed n-3 fatty acid-deficient diet compared to the rats fed n-3 fatty acid-adequate diet. This study suggest that brain DHA level can be decreased in male rats fed n-3 fatty acid-deficient diet during post-weaning period, and the decreased brain DHA is associated with higher stress-induced serum corticosterone levels.

中文摘要 I
英文摘要 II
圖目錄 VI
表目錄 VIII
第壹章、文獻回顧 1
第一節、二十二碳六烯酸 1
第二節、必需脂肪酸的生合成 2
第三節、二十二碳六烯酸與憂鬱症 3
第四節、下視丘-腦下垂體-腎上腺路徑 4
第五節、HPA axis與憂鬱症 5
第六節、壓力模式的選擇 7
第七節、缺乏DHA的動物模式 9
第貳章、實驗目的與假設 11
第參章、材料與方法 12
一、 實驗設計 12
二、 實驗用飼料配方與分析 13
1. 自製實驗飼料組成 14
2. 飼料脂肪酸組成比較 15
三、 行為實驗 16
1. 抬高型十字迷宮實驗 (Elevated plus-maze) 16
2. 強迫游泳實驗(Forced swim test) 17
四、 束縛壓力實驗(Restraint stress) 18
五、 動物犧牲與組織收集 19
六、 脂肪酸檢測分析 19
1. 藥品來源 19
2. 分析流程 20
七、 糖皮質類固醇酵素免疫分析 22
八、 腦組織中GR及BDNF蛋白表現分析 24
1. 蛋白質萃取 24
2. 蛋白質定量 25
3. 電泳檢定-西方墨點法 (Western blot) 25
4. 轉印 27
5. 酵素免疫染色法 28
6. 冷光照相與定量 29
九、 統計分析 29
第肆章、實驗結果 30
一、 脂肪酸組成分析 30
二、 動物焦慮程度之檢測 37
三、 動物憂鬱程度之檢測 38
四、 動物經束縛壓力之肛溫變化 39
五、 血清中corticosterone之測量 41
六、 海馬及下視丘中GR蛋白之表現 42
七、 海馬及下視丘中BDNF蛋白之表現 43
第伍章、討論 45
一、 動物模式的選擇 45
二、 離乳後缺乏n-3 PUFA對大鼠DHA含量的影響 46
三、 離乳後缺乏n-3 PUFA對大鼠情緒的影響 49
四、 離乳後缺乏n-3 PUFA對大鼠遭遇壓力之反應的影響 50
五、 離乳後缺乏n-3 PUFA對大鼠海馬及下視丘GR表現的影響 52
第陸章、總結 54
Appendix 55
1. 初始實驗設計及動物數量分配 55
1-1. 實驗設計 55
1-2. 實驗動物數量分配 56
2. 大鼠出生後體重及10周大雄性大鼠體重及腦重 57
3. 十字迷宮實驗 58
4. 強迫游泳實驗 59
5. 動物經束縛壓力之肛溫變化 60
6. 血清中corticosterone濃度變化 61
參考文獻 62

Armario A, Gavalda A, Marti J (1995) Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology 20:879-890.
Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu E-E, Schold C, Schatzberg AF (2002) An open label trial of C-1073 (mifepristone) for psychotic major depression*. Biological Psychiatry 52:386-392.
Belzung C, Leguisquet A-M, Barreau S, Delion-Vancassel S, Chalon S, Durand G (1998) α-Linolenic Acid Deficiency Modifies Distractibility but Not Anxiety and Locomotion in Rats during Aging. The Journal of Nutrition 128:1537-1542.
Bourre J-ME, Dumont OS, Piciotti MJ, Pascal GA, Durand GA (1992) Dietary α-linolenic acid deficiency in adult rats for 7 months does not alter brain docosahexaenoic acid content, in contrast to liver, heart and testes. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1124:119-122.
Bouwstra H, Dijck-Brouwer DJ, Wildeman JA, Tjoonk HM, van der Heide JC, Boersma ER, Muskiet FA, Hadders-Algra M (2003) Long-chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants. The American Journal of Clinical Nutrition 78:313-318.
Carroll BJ (1985) Dexamethasone suppression test: A review of contemporary confusion. Journal of Clinical Psychiatry 46:13-24.
Castren E (2005) Is mood chemistry? Nat Rev Neurosci 6:241-246.
Checkley S (1996) The neuroendocrinology of depression and chronic stress. British Medical Bulletin 52:597-617.
Chen H-F, Su H-M (2012) Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect. The Journal of Nutritional Biochemistry 23:299-305.
Chen H-F, Su H-M (2013) Exposure to a maternal n-3 fatty acid-deficient diet during brain development provokes excessive hypothalamic–pituitary–adrenal axis responses to stress and behavioral indices of depression and anxiety in male rat offspring later in life. The Journal of Nutritional Biochemistry 24:70-80.
Chrousos Gp GPW (1992) The concepts of stress and stress system disorders: Overview of physical and behavioral homeostasis. JAMA: The Journal of the American Medical Association 267:1244-1252.
Chung W-L, Chen J-J, Su H-M (2008) Fish Oil Supplementation of Control and (n-3) Fatty Acid-Deficient Male Rats Enhances Reference and Working Memory Performance and Increases Brain Regional Docosahexaenoic Acid Levels. The Journal of Nutrition 138:1165-1171.
DeMar JC, Ma K, Bell JM, Igarashi M, Greenstein D, Rapoport SI (2006) One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats. Journal of Lipid Research 47:172-180.
Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Human Development 3:79-83.
Dullemeijer C, Durga J, Brouwer IA, van de Rest O, Kok FJ, Brummer R-JM, van Boxtel MP, Verhoef P (2007) n−3 Fatty acid proportions in plasma and cognitive performance in older adults. The American Journal of Clinical Nutrition 86:1479-1485.
Duman RS, Monteggia LM (2006) A Neurotrophic Model for Stress-Related Mood Disorders. Biological Psychiatry 59:1116-1127.
Favreliere S, Stadelmann-Ingrand S, Huguet F, De Javel D, Piriou A, Tallineau C, Durand G (2000) Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus. Neurobiology of Aging 21:653-660.
Feldman S, Conforti N, Weidenfeld J (1995) Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical responses to neural stimuli. Neuroscience & Biobehavioral Reviews 19:235-240.
Feldman S, Weidenfeld J (1998) The Excitatory Effects of the Amygdala on Hypothalamo-Pituitary-Adrenocortical Responses Are Mediated by Hypothalamic Norepinephrine, Serotonin, and CRF-41. Brain Research Bulletin 45:389-393.
Folch J, Lees M, Stanley GHS (1957) A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES. Journal of Biological Chemistry 226:497-509.
Gadek-Michalska A, Bugajski J (2003) Repeated handling, restraint, or chronic crowding impair the hypothalamic-pituitary-adrenocortical response to acute restraint stress. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 54:449-459.
Ghosh A, Carnahan J, Greenberg ME (1994) Requirement for BDNF in activity-dependent survival of cortical neurons. Science (New York, NY) 263:1618-1623.
Giusto NM, Salvador GA, Castagnet PI, Pasquare SJ, Ilincheta de Boschero MG (2002) Age-Associated Changes in Central Nervous System Glycerolipid Composition and Metabolism. Neurochem Res 27:1513-1523.
Green P, Glozman S, Kamensky B, Yavin E (1999) Developmental changes in rat brain membrane lipids and fatty acids: the preferential prenatal accumulation of docosahexaenoic acid. Journal of Lipid Research 40:960-966.
Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA (2003) Maternal Supplementation With Very-Long-Chain n-3 Fatty Acids During Pregnancy and Lactation Augments Children’s IQ at 4 Years of Age. Pediatrics 111:e39-e44.
Herman JP, Prewitt CM, Cullinan WE (1996) Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress axis. Critical reviews in neurobiology 10:371-394.
Hibbeln JR (1998) Fish consumption and major depression. The Lancet 351:1213.
Hibbeln JR (2002) Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. Journal of Affective Disorders 69:15-29.
Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression: implicatons for therapy. Journal of Affective Disorders 62:77-91.
Holsboer F, Barden N (1996) Antidepressants and Hypothalamic-Pituitary-Adrenocortical Regulation. Endocrine Reviews 17:187-205.
Innis SM (2003) Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. The Journal of Pediatrics 143:1-8.
Innis SM, Friesen RW (2008) Essential n−3 fatty acids in pregnant women and early visual acuity maturation in term infants. The American Journal of Clinical Nutrition 87:548-557.
Jessop DS (1999) Stimulatory and inhibitory regulators of the hypothalamo–pituitary–adrenocortical axis. Best Practice & Research Clinical Endocrinology & Metabolism 13:491-501.
Kalmijn S, van Boxtel MPJ, Ocke M, Verschuren WMM, Kromhout D, Launer LJ (2004) Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 62:275-280.
Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. The American journal of psychiatry 156:837-848.
Kodas E, Galineau L, Bodard S, Vancassel S, Guilloteau D, Besnard J-C, Chalon S (2004) Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat. Journal of Neurochemistry 89:695-702.
Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894-902.
Lafourcade M, Larrieu T, Mato S, Duffaud A, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodriguez-Puertas R, Laye S, Manzoni OJ (2011) Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci 14:345-350.
Levant B, Ozias MK, Davis PF, Winter M, Russell KL, Carlson SE, Reed GA, McCarson KE (2008) Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats. Psychoneuroendocrinology 33:1279-1292.
Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress. Science 277:1659-1662.
Maes M, Lin A, Bonacccorso S, Van Hunsel F, Gastel AV, Delmeire L, Biondi M, Bosmans E, Kenis G, Scharpe S (1998) Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not h patients with fibromyalgia. Acta Psychiatrica Scandinavica 98:328-335.
Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD (1990) Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science (New York, NY) 247:1446-1451.
Mamalakis G, Tornaritis M, Kafatos A (2002) Depression and adipose essential polyunsaturated fatty acids. Prostaglandins, Leukotrienes and Essential Fatty Acids 67:311-318.
Martinez M (1992) Tissue levels of polyunsaturated fatty acids during early human development. The Journal of Pediatrics 120:S129-S138.
Matthews SG (2002) Early programming of the hypothalamo–pituitary–adrenal axis. Trends in Endocrinology & Metabolism 13:373-380.
McNamara RK, Able J, Liu Y, Jandacek R, Rider T, Tso P, Lipton JW (2009) Omega-3 fatty acid deficiency during perinatal development increases serotonin turnover in the prefrontal cortex and decreases midbrain tryptophan hydroxylase-2 expression in adult female rats: Dissociation from estrogenic effects. Journal of Psychiatric Research 43:656-663.
McNamara RK, Hahn C-G, Jandacek R, Rider T, Tso P, Stanford KE, Richtand NM (2007) Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder. Biological Psychiatry 62:17-24.
Meaney MJ (2001) MATERNAL CARE, GENE EXPRESSION, AND THE TRANSMISSION OF INDIVIDUAL DIFFERENCES IN STRESS REACTIVITY ACROSS GENERATIONS. Annual Review of Neuroscience 24:1161-1192.
Modell S, Yassouridis A, Huber J, Holsboer F (1997) Corticosteroid receptor function is decreased in depressed patients. Neuroendocrinology 65:216-222.
Mohrhauer H, Holman RT (1963) ALTERATION OF THE FATTY ACID COMPOSITION OF BRAIN LIPIDS BY VARYING LEVELS OF DIETARY ESSENTIAL FATTY ACJDS*. Journal of Neurochemistry 10:523-530.
Moriguchi T, Greiner RS, Salem N (2000) Behavioral Deficits Associated with Dietary Induction of Decreased Brain Docosahexaenoic Acid Concentration. Journal of Neurochemistry 75:2563-2573.
Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E (2005) Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neuroscience Research 53:129-139.
Nurk E, Drevon CA, Refsum H, Solvoll K, Vollset SE, Nygard O, Nygaard HA, Engedal K, Tell GS, Smith AD (2007) Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study. The American Journal of Clinical Nutrition 86:1470-1478.
Owens SdlP, Innis SM (1999) Docosahexaenoic and Arachidonic Acid Prevent a Decrease in Dopaminergic and Serotoninergic Neurotransmitters in Frontal Cortex Caused by a Linoleic and α-Linolenic Acid Deficient Diet in Formula-fed Piglets. The Journal of Nutrition 129:2088-2093.
Papakonstantinou E, Ryan DH, Harris RBS (2003) Dietary fish oil does not protect rats exposed to restraint or sleep deprivation stress. Physiology & Behavior 78:759-765.
Parker G, Gibson NA, Brotchie H, Heruc G, Rees AM, Hadzi-Pavlovic D (2006) Omega-3 fatty acids and mood disorders. The American journal of psychiatry 163:969-978.
Pearson Murphy BE (1991) Steroids and depression. The Journal of Steroid Biochemistry and Molecular Biology 38:537-559.
Peet M, Murphy B, Shay J, Horrobin D (1998) Depletion of Omega-3 Fatty Acid Levels in Red Blood Cell Membranes of Depressive Patients. Biological Psychiatry 43:315-319.
Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. European Journal of Neuroscience 17:879-886.
Phillips LJ, McGorry PD, Garner B, Thompson KN, Pantelis C, Wood SJ, Berger G (2006) Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications for the development of psychotic disorders. Australian and New Zealand Journal of Psychiatry 40:725-741.
Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. The Journal of Nutrition 123:1939-1951.
Retana-Marquez S, Bonilla-Jaime H, Vazquez-Palacios G, Dominguez-Salazar E, Martinez-Garcia R, Velazquez-Moctezuma J (2003) Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats. Psychoneuroendocrinology 28:207-227.
Reul JMHM, Kloet ERD (1985) Two Receptor Systems for Corticosterone in Rat Brain: Microdistribution and Differential Occupation. Endocrinology 117:2505-2511.
Rotstein NP, Ilincheta de Boschero MG, Giusto NM, Aveldano MI (1987) Effects of aging on the composition and metabolism of docosahexaenoate-containing lipids of retina. Lipids 22:253-260.
Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000) Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 101:305-312.
Soderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26:421-425.
Sapolsky RM (1985) Glucocorticoid toxicity in the hippocampus: Temporal aspects of neuronal vulnerability. Brain Research 359:300-305.
Sapolsky RM (1996) Why stress is bad for your brain. Science 273:749-750.
Sapolsky RM, Romero LM, Munck AU (2000) How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions. Endocrine Reviews 21:55-89.
Sastry PS (1985) Lipids of nervous tissue: composition and metabolism. Progress in lipid research 24:69-176.
Schaaf MJM, de Jong J, de Kloet ER, Vreugdenhil E (1998) Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone. Brain Research 813:112-120.
Schaefer E, Bongard V, Beiser AS (2006) Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and alzheimer disease: The framingham heart study. Archives of Neurology 63:1545-1550.
Scott BL, Bazan NG (1989) Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proceedings of the National Academy of Sciences 86:2903-2907.
Selye H (1936) A syndrome produced by diverse nocuous agents. Nature 138:32.
Shirayama Y, Chen AC-H, Nakagawa S, Russell DS, Duman RS (2002) Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression. The Journal of Neuroscience 22:3251-3261.
Smith M, Makino S, Kvetnansky R, Post R (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. The Journal of Neuroscience 15:1768-1777.
Su H-M (2010) Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. The Journal of Nutritional Biochemistry 21:364-373.
Swaab DF, Bao A-M, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Research Reviews 4:141-194.
Takeuchi T, Iwanaga M, Harada E (2003) Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Research 964:136-143.
Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamaki H, Lehtonen J, Vartiainen E (2001) Fish consumption and depressive symptoms in the general population in Finland. Psychiatric services (Washington, DC) 52:529-531.
Tarullo AR, Gunnar MR (2006) Child maltreatment and the developing HPA axis. Hormones and Behavior 50:632-639.
Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM (2003) Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. The American Journal of Clinical Nutrition 78:40-46.
Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ (2003) Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer''s disease: a case-control study. The British journal of nutrition 89:483-489.
Ueyama T, Kawai Y, Nemoto K, Sekimoto M, Tone S, Senba E (1997) Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain. Neuroscience Research 28:103-110.
Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: A meta-analysis of MRI studies. The American journal of psychiatry 161:1957-1966.
Walker JJ, Terry JR, Lightman SL (2010) Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis. Proceedings of the Royal Society B: Biological Sciences 277:1627-1633.
Weber B, Lewicka S, Deuschle M, Colla M, Vecsei P, Heuser I (2000) Increased Diurnal Plasma Concentrations of Cortisone in Depressed Patients. Journal of Clinical Endocrinology & Metabolism 85:1133-1136.
Xiao Y, Huang Y, Chen ZY (2005) Distribution, depletion and recovery of docosahexaenoic acid are region-specific in rat brain. The British journal of nutrition 94:544-550.
Yamano Y, Yoshioka M, Toda Y, Oshida Y, Chaki S, Hamamoto K, Morishima I (2004) Regulation of CRF, POMC and MC4R gene expression after electrical foot shock stress in the rat amygdala and hypothalamus. The Journal of veterinary medical science / the Japanese Society of Veterinary Science 66:1323-1327.
Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI (1998) Fatty Acids and Brain Peptides. Peptides 19:407-419.
陳人睿 (2007) 探討雌激素對腦區二十二碳六烯酸含量與空間學習記憶之影響. 國立台灣大學醫學院生理學研究所碩士論文.