Hormone im Alter: Epigenetische Kontrolle und Enhancement der Kognition

Alexander Römmler

doi:10.1055/s-0034-1383250

Zeitschrift für Orthomolekulare Medizin, Table of Contents

Zeitschrift für Orthomolekulare Medizin 2014; 12(4): 14-19
DOI: 10.1055/s-0034-1383250

Wissen

Hippokrates Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG Stuttgart · New York

Hormone im Alter: Epigenetische Kontrolle und Enhancement der Kognition

Alexander Römmler

Abstract

Zusammenfassung

Kognitionseinschränkungen im Alter sind auf nachlassende Neurogenese zurückzuführen und stehen unter epigenetischer Kontrolle. In Prävention und Therapie stellt neben Maßnahmen der Lebensführung insbesondere das Neurosteroid-Replacement eine erfolgversprechende Option dar.

Schlüsselwörter

Alter - Neurogenese - epigenetische Kontrolle - Kognition - Umgebungsreize - Neurosteroidhormone - Pregnenolon - DHEA - Progesteron - Replacement

Full Text

References

Literatur
1 Aberg D. Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis. Endocr Dev 2010; 17: 63-76
2 Adamusová E, Cais O, Vyklický V et al. Pregnenolone sulfate activates NMDA receptor channels. Physiol Res 2013; 62 (6) 731-736
3 Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A. Loss of HDAC5 impairs memory function: implications for Alzheimerʼs disease. J Alzheimers Dis 2013; 33 (1) 35-44
4 Akwa Y, Baulieu EE. Neurosteroids: behavioral aspects and physiological implications. J Soc Biol 1999; 193 (3) 293-298
5 Algattas H, Huang JH. Traumatic Brain Injury pathophysiology and treatments: early, intermediate, and late phases post-injury. Int J Mol Sci 2013; 15 (1) 309-341
6 Anderson MF, Aberg MA, Nilsson M, Eriksson PS. Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res Dev Brain Res 2002; 134(1–2): 115-122
7 Azizi H, Mehrjardi NZ, Shahbazi E et al. Dehydroepiandrosterone stimulates neurogenesis in mouse embryonal carcinoma cell- and human embryonic stem cell-derived neural progenitors and induces dopaminergic neurons. Stem Cells Dev 2010; 19 (6) 809-818
8 Banasr M, Duman RS. Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets 2007; 6 (5) 311-320
9 Belelli D, Herd MB, Mitchell EA et al. Neuroactive steroids and inhibitory neurotransmission: mechanisms of action and physiological relevance. Neuroscience 2006; 138 (3) 821-829
10 Berg DA, Belnoue L, Song H, Simon A. Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development 2013; 140 (12) 2548-2561
11 Bergami M, Berninger B. A fight for survival: the challenges faced by a newborn neuron integrating in the adult hippocampus. Dev Neurobiol 2012; 72 (7) 1016-1031
12 Brown ES, Park J, Marx CE et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression. Neuropsychopharmacology 2014; Jun 11 [Epub ahead of print]
13 Bunk EC, Stelzer S, Hermann S et al. Cellular organization of adult neurogenesis in the Common Marmoset. Aging Cell 2011; 10 (1) 28-38
14 Calvanese V, Fraga MF. SirT1 brings stemness closer to cancer and aging. Aging (Albany NY) 2011; 3 (2) 162-167
15 Charalampopoulos I, Alexaki VI, Tsatsanis C et al. Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging. Ann N Y Acad Sci 2006; 1088: 139-152
16 Charalampopoulos I, Remboutsika E, Margioris AN, Gravanis A. Neurosteroids as modulators of neurogenesis and neuronal survival. Trends Endocrinol Metab 2008; 19 (8) 300-307
17 Caufriez A, Leproult R, LʼHermite-Balériaux M et al. Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women. J Clin Endocrinol Metab 2011; 96 (4) E614-623
18 Cheng MF. Hypothalamic neurogenesis in the adult brain. Front Neuroendocrinol 2013; 34 (3) 167-178
19 Conboy IM, Conboy MJ, Wagers AJ et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 2005; 433 (7027) 760-764
20 Couillard-Despres S, Iglseder B, Aigner L. Neurogenesis, cellular plasticity and cognition: the impact of stem cells in the adult and aging brain – a mini-review. Gerontology 2011; 57 (6) 559-564
21 Davis PK, Brackmann RK. Chromatin remodeling and cancer. Cancer Biol Ther 2003; 2 (1) 22-29
22 De Lignieres B, Dennerstein L, Backstrom T. Influence of route of administration on progesterone metabolism. Maturitas 1995; 21: 251-257
23 De Nicola AF, Gonzalez-Deniselle MC, Garay L et al. Progesterone Protective Effects In Neurodegeneration And Neuroinflammation. J Neuroendocrinol 2013; 25 (11) 1095-1103
24 Déry N, Pilgrim M, Gibala M et al. Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression. Front Neurosci 2013; 7: 66
25 Fabel K, Kempermann G. Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromolecular Med 2008; 10 (2) 59-66
26 Fischer A, Sananbenesi F, Wang X et al. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007; 447 (7141) 178-182
27 Garcia-Segura LM, Arévalo MA, Azcoitia I. Interactions of estradiol and insulin-like growth factor-I signalling in the nervous system: new advances. Prog Brain Res 2010; 181: 251-272
28 Genazzani AD, Stomati M, Bernardi F et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril 2003; 80: 1495-1501
29 Genazzani AR, Inglese S, Lombardi I et al. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male 2004; 7: 133-143
30 Glasper ER, Llorens-Martin MV, Leuner B et al. Blockade of insulin-like growth factor-I has complex effects on structural plasticity in the hippocampus. Hippocampus 2010; 20 (6) 706-712
31 Gräff J, Rei D, Guan JS et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012; 483 (7388) 222-226
32 Gu Y, Janoschka S, Ge S. Neurogenesis and hippocampal plasticity in adult brain. Curr Top Behav Neurosci 2013; 15: 31-48
33 Guan JS, Haggarty SJ, Giacometti E et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459 (7243) 55-60
34 Guan JS, Xie H, Ding X. The role of epigenetic regulation in learning and memory. Exp Neurol 2014; May 14 [Epub ahead of print]
35 Gunn BG, Cunningham L, Mitchell SG et al. GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response. Front Neuroendocrinol 2014; Jun 12 [Epub ahead of print]
36 Harteneck C. Pregnenolone sulfate: from steroid metabolite to TRP channel ligand. Molecules 2013; 18 (10) 12012-12028
37 Jenwitheesuk A, Nopparat C, Mukda S et al. Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways. Int J Mol Sci 2014; 15 (9) 16848-16884
38 Kawano H et al. DHEA-Supplementation improves endothelial function and insulin sensitivty in men. JCEM 2003; 88: 3190-3195
39 Kim D, Nguyen MD, Dobbin MM et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimerʼs disease and amyotrophic lateral sclerosis. EMBO J 2007; 26 (13) 3169-3179
40 Klempin F, Beis D, Mosienko V et al. Serotonin is required for exercise-induced adult hippocampal neurogenesis. J Neurosci 2013; 33 (19) 8270-8275
41 Koenig H, Schumacher M, Ferzaz B et al. Progesterone synthesis and myelin formation by Schwann cells. Science 1995; 268: 1500-1503
42 Koenig H, Gong WH, Pelissier P. Role of progesterone in peripheral nerve repair. Rev Reprod 2000; 5: 189-199
43 Kreinin A, Bawakny N, Ritsner MS. Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia. Clin Schizophr Relat Psychoses 2014; 4: 1-31
44 Krugers HJ, Lucassen PJ, Karst H, Joëls M. Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment. Front Synaptic Neurosci 2010; 2: 24
45 Leuner B, Kozorovitskiy Y, Gross CG, Gould E. Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci USA 2007; 104 (43) 17169-17173
46 Llorens-Martín M, Torres-Alemán I, Trejo JL. Exercise modulates insulin-like growth factor 1-dependent and -independent effects on adult hippocampal neurogenesis and behaviour. Mol Cell Neurosci 2010; 44 (2) 109-117
47 Lucassen PJ, Meerlo P, Naylor AS et al. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacol 2010; 20 (1) 1-17
48 Marx CE, Keefe RS, Buchanan RW et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009; 34 (8) 1885-1903
49 Marx CE, Bradford DW, Hamer RM et al. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience 2011; 191: 78-90
50 Mayo W, Lemaire V, Malaterre J et al. Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus. Neurobiol Aging 2005; 26 (1) 103-114
51 Melcangi RC, Giatti S, Calabrese D et al. Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions. Prog Neurobiol 2014; 113: 56-69
52 Miyamoto E. Molecular mechanism of neuronal plasticity: induction and maintenance of long-term potentiation in the hippocampus. J Pharmacol Sci 2006; 100 (5) 433-442
53 Michán S, Li Y, Chou MM et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 2010; 30 (29) 9695-9707
54 Mikaelsson MA, Miller CA. The path to epigenetic treatment of memory disorders. Neurobiol Learn Mem 2011; 96 (1) 13-18
55 Miller CA, Campbell SL, Sweatt JD. DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol Learn Mem 2008; 89 (4) 599-603
56 Mirochnic S, Wolf S, Staufenbiel M, Kempermann G. Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease. Hippocampus 2009; 19 (10) 1008-1018
57 Naylor JC, Kilts JD, Hulette CM et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimerʼs disease compared to cognitively intact control subjects. Biochim Biophys Acta 2010; 1801 (8) 951-959
58 Pathipati P, Gorba T, Scheepens A et al. Growth hormone and prolactin regulate human neural stem cell regenerative activity. Neuroscience 2011; 190: 409-427
59 Peleg S, Sananbenesi F, Zovoilis A et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 2010; 328 (5979) 753-756
60 Peixoto L, Abel T. The role of histone acetylation in memory formation and cognitive impairments. Neuropsychopharmacology 2013; 38 (1) 62-76
61 Ponti G, Obernier K, Guinto C et al. Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci USA 2013; 110 (11) E1045-1054
62 Ponti G, Obernier K, Alvarez-Buylla A. Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone. Cell Cycle 2013; 12 (11) 1649-1650
63 Reddy DS. Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog Brain Res 2010; 186: 113-137
64 Ritsner MS, Bawakny H, Kreinin A. Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial. Psychiatry Clin Neurosci 2014; 68 (6) 432-440
65 Römmler A, Römmler J. Progesteron – genitale und extragenitale Wirkungen. Zs f Orthomol Med 2009; 3: 9-13
66 Römmler A, Römmler-Zehrer J. Adrenopause – Die Rolle des Schlüsselhormons DHEA. gynäkologie + geburtshilfe gg 2013; 18 (SH1) 34-39
67 Römmler A. Neurosteroid-Replacement-Therapie mit Pregnenolon, Progesteron und DHEA. Menopause – Andropause – Anti-Aging, Wien 2010. J Gynäkol Endokrinol 2010; 13 (4) 42
68 Römmler A Hrsg. Hormone – Leitfaden für die Anti-Aging-Sprechstunde. München: Thieme; 2014
69 Römmler A. Pregnenolon – die Schlüsselrolle des ersten Steroidhormons. In: Römmler A, Hrsg. Hormone – Leitfaden für die Anti-Aging-Sprechstunde. München: Thieme; 2014: 137-153
70 Römmler A. DHEA und Adrenopause. In: Römmler A, Hrsg. Hormone – Leitfaden für die Anti-Aging-Sprechstunde. München: Thieme; 2014: 19-33
71 Römmler A. Progesteron, ein systemisch wirkendes Hormon bei Mann und Frau. In: Römmler A, Hrsg. Hormone – Leitfaden für die Anti-Aging-Sprechstunde. München: Thieme; 2014: 123-136
72 Rodríguez JJ, Noristani HN, Olabarria M et al. Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimerʼs disease. Curr Alzheimer Res 2011; 8 (7) 707-717
73 Sahay A, Scobie KN, Hill AS et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 2011; 472 (7344) 466-470
74 Schmidt PJ, Daly RC, Bloch M et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005; 62: 154-162
75 Schumacher M, Baulieu EE. Neurosteroids: synthesis and functions in the central and peripheral nervous systems. Ciba Found Symp 1995; 191: 90-106 discussion 106–112
76 Schumacher M, Guennoun R, Ghoumari A et al. Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system. Endocr Rev 2007; 28: 387-439
77 Schumacher M, Guennoun R, Robert F et al. Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Growth Horm IGF Res 2004; 14 (Suppl A) S18-S33
78 Schumacher M, Hussain R, Gago N et al. Progesterone synthesis in the nervous system: implications for myelination and myelin repair. Front Neurosci 2012; 6: 10
79 Schumacher M, Mattern C, Ghoumari A et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Prog Neurobiol 2014; 113: 6-39
80 Schumacher M, Robel P, Baulieu EE. Development and regeneration of the nervous system: a role for neurosteroids. Dev Neurosci 1996; 18: 6-21
81 Schumacher M, Weill-Engerer S, Liere P et al. Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 2003; 71: 3-29
82 Stein DG. Progesterone in the treatment of acute traumatic brain injury: a clinical perspective and update. Neuroscience 2011; 191: 101-106
83 Stilling RM, Fischer A. The role of histone acetylation in age-associated memory impairment and Alzheimerʼs disease. Neurobiol Learn Mem 2011; 96 (1) 19-26
84 Suzuki M, Wright LS, Marwah P et al. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. Proc Natl Acad Sci USA 2004; 101 (9) 3202-3207
85 Vallée M, Mayo W, Darnaudéry M et al. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci USA 1997; 94: 14865-14870
86 Villeda SA, Luo J, Mosher KI et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 2011; 477 (7362) 90-94
87 Villeda SA, Wyss-Coray T. The circulatory systemic environment as a modulator of neurogenesis and brain aging. Autoimmun Rev 2013; 12 (6) 674-677
88 Williams MR, Dawood T, Ling S et al. Dehydroepiandrosterone increases endothelial cell proliferation in vitro and improves endothelial function in vivo by mechanisms independent of androgen and estrogen receptors. J Clin Endocrinol Metab 2004; 89 (9) 4708-4715
89 Xiao G, Wei J, Yan W et al. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 2008; 12 (2) R61
90 Yamada S, Akishita M, Fukai S et al. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr Gerontol Int 2010; 10: 280-287

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