Neurosteroids as regenerative agents in the brain: Therapeutic implications

Nature Reviews Endocrinology

Volumn 9, Issue 4, 2013, Pages 241-250

  Brinton, Roberta D ^a,b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID A RECEPTOR; AMYLOID BETA PROTEIN; CALCIUM CHANNEL L TYPE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYCLIN A; CYCLIN B; CYCLIN D1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 4; CYCLIN E; LIVER X RECEPTOR; MYELIN; NEUROSTEROID; PREGNANE X RECEPTOR; PROTEIN P16; PROTEIN P18; PROTEIN P27; UBIQUITIN PROTEIN LIGASE;

AGING; ALZHEIMER DISEASE; CELL ACTIVATION; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CELL REGENERATION; CELL RENEWAL; CENTRAL NERVOUS SYSTEM; DEGENERATIVE DISEASE; DOWN REGULATION; DRUG EFFICACY; EXPERIMENTAL MOUSE; HIPPOCAMPUS; HUMAN; LEARNING; MEMBRANE DEPOLARIZATION; MEMORY; MICROGLIA; NERVOUS SYSTEM; NONHUMAN; PERIPHERAL NERVOUS SYSTEM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGENERATIVE MEDICINE; REVIEW; SURVIVAL; TISSUE REGENERATION; UPREGULATION; WHITE MATTER;

ALZHEIMER DISEASE; ANIMALS; BRAIN; HUMANS; NEUROTRANSMITTER AGENTS; PREGNANOLONE;

EID: 84875420499     PISSN: 17595029     EISSN: 17595037     Source Type: Journal    
DOI: 10.1038/nrendo.2013.31     Document Type: Review

References (78)

1. Baulieu, E. E. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog. Horm. Res. 52, 1-32 (1997).
2. Baulieu, E. E. & Schumacher, M. Neurosteroids, with special reference to the effect of progesterone on myelination in peripheral nerves. Mult. Scler. 3, 105-112 (1997).
3. Melcangi, R. C. & Panzica, G. Neuroactive steroids: an update of their roles in central and peripheral nervous system. Psychoneuroendocrinology 34 (Suppl 1), S1-S8 (2009).
4. Mellon, S. H. & Griffin, L. D. Neurosteroids: biochemistry and clinical significance. Trends Endocrinol. Metab. 13, 35-43 (2002).
5. Bishop, N. A., Lu, T. & Yankner, B. A. Neural mechanisms of ageing and cognitive decline. Nature 464, 529-535 (2010).
6. Skovronsky, D. M., Lee, V. M. & Trojanowski, J. Q. Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu. Rev. Pathol. 1, 151-170 (2006).
7. Encinas, J. M. et al. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8, 566-579 (2011).
8. Kuhn, H. G., Dickinson-Anson, H. & Gage, F. H. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027-2033 (1996).
9. Lazarov, O., Mattson, M. P., Peterson, D. A., Pimplikar, S. W. & van Praag, H. When neurogenesis encounters aging and disease. Trends Neurosci. 33, 569-579 (2010).
10. Lugert, S. et al. Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6, 445-456 (2010).
11. Lugert, S. & Taylor, V. Neural stem cells: disposable, end-state glia? Cell Stem Cell 8, 464-465 (2011).
12. Singh, C. et al. Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3×TgAD and nonTg mice. Neurobiol. Aging 33, 1493-1506 (2012).
13. Wang, J. M. et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proc. Natl Acad. Sci. USA 107, 6498-6503 (2010).
14. Rodriguez, J. J. et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease. PLoS ONE 3, e2935 (2008).
15. Brinton, R. D. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends Neurosci. 31, 529-537 (2008).
16. Brinton, R. D. Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Pharmacol. Sci. 30, 212-222 (2009).
17. Naylor, J. C. et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects. Biochim. Biophys. Acta 1801, 951-959 (2010).
18. Yang, S. Y., He, X. Y. & Schulz, H. Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol. Metab. 16, 167-175 (2005).
19. Herrup, K. & Yang, Y. Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat. Rev. Neurosci. 8, 368-378 (2007).
20. Schumacher, M. et al. Progesterone synthesis in the nervous system: implications for myelination and myelin repair. Front. Neurosci. 6, 10 (2012).
21. Sun, C. et al. Allopregnanolone increases the number of dopaminergic neurons in substantia nigra of a triple transgenic mouse model of Alzheimer's disease. Curr. Alzheimer Res. 9, 473-480 (2012).
22. Wang, J. M., Johnston, P. B., Ball, B. G. & Brinton, R. D. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J. Neurosci. 25, 4706-4718 (2005).
23. Melcangi, R. C. et al. Role of neuroactive steroids in the peripheral nervous system. Front. Endocrinol. (Lausanne) 2, 104 (2011).
24. Deng, W., Saxe, M. D., Gallina, I. S. & Gage, F. H. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J. Neurosci. 29, 13532-13542 (2009).
25. Rodriguez, J. J., Jones, V. C. & Verkhratsky, A. Impaired cell proliferation in the subventricular zone in an Alzheimer's disease model. Neuroreport 20, 907-912 (2009).
26. Haughey, N. J. et al. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromolecular Med. 1, 125-135 (2002).
27. Aimone, J. B., Deng, W. & Gage, F. H. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70, 589-596 (2011).
28. Deng, W., Aimone, J. B. & Gage, F. H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11, 339-350 (2010).
29. Shors, T. J., Townsend, D. A., Zhao, M., Kozorovitskiy, Y. & Gould, E. Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12, 578-584 (2002).
30. Shors, T. J. et al. Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372-376 (2001).
31. Bartzokis, G. Alzheimer's disease as homeostatic responses to age-related myelin breakdown. Neurobiol. Aging 32, 1341-1371 (2011).
32. Kuczynski, B. et al. White matter integrity and cortical metabolic associations in aging and dementia. Alzheimers Dement. 6, 54-62 (2010).
33. Ringman, J. M. et al. Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations. Brain 130, 1767-1776 (2007).
34. Yao, J., Rettberg, J. R., Klosinski, L. P., Cadenas, E. & Brinton, R. D. Shift in brain metabolism in late onset Alzheimer's disease: implications for biomarkers and therapeutic interventions. Mol. Aspects Med. 32, 247-257 (2011).
35. Chen, S. et al. Allopregnanolone promotes regeneration and reduces beta-amyloid burden in a preclinical model of Alzheimer's disease. PLoS ONE 6, e24293 (2011).
36. Desai, M. K. et al. Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Glia 57, 54-65 (2009).
37. Saher, G. et al. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci. 8, 468-475 (2005).
38. Rupprecht, R. et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 9, 971-988 (2010).
39. Bateman, R. J. et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N. Engl. J. Med. 367, 795-804 (2012).
40. Reitz, C., Brayne, C. & Mayeux, R. Epidemiology of Alzheimer disease. Nat. Rev. Neurol. 7, 137-152 (2011).
41. Jack, C. R. Jr. et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 9, 119-128 (2010).
42. Reiman, E. M. & Jagust, W. J. Brain imaging in the study of Alzheimer's disease. Neuroimage 61, 505-516 (2012).
43. Weiner, M. W. et al. The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers. Dement. 8 (Suppl 1 ) S1-68 (2012).
44. Lesne, S. et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440, 352-357 (2006).
45. De Strooper, B., Vassar, R. & Golde, T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat. Rev. Neurol. 6, 99-107 (2010).
46. Irwin, R. W., Wang, J. M., Chen, S. & Brinton, R. D. Neuroregenerative mechanisms of allopregnanolone in Alzheimer's disease. Front. Endocrinol. (Lausanne) 2, 117 (2011).
47. Kang, J. & Rivest, S. Lipid metabolism and neuroinflammation in Alzheimer's disease: a role for liver X receptors. Endocr. Rev. 33, 2011-1049 (2012).
48. Mandrekar-Colucci, S., Karlo, J. C. & Landreth, G. E. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-gamma-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J. Neurosci. 32, 10117-10128 (2012).
49. Repa, J. J. et al. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J. Neurosci. 27, 14470-14480 (2007).
50. Cramer, P. E. et al. ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335, 1503-1506 (2012).
51. Riddell, D. R. et al. The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Mol. Cell Neurosci. 34 621-628 (2007).
52. Langmade, S. J. et al. Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc. Natl Acad. Sci. USA 103, 13807-13812 (2006).
53. Kliewer, S. A. & Willson, T. M. Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. J. Lipid Res. 43, 359-364 (2002).
54. Willson, T. M. & Kliewer, S. A. PXR, CAR and drug metabolism. Nat. Rev. Drug Discov. 1, 259-266 (2002).
55. Porter, F. D. et al. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci. Transl. Med. 2, 56ra81 (2010).
56. Hagemeyer, C. E., Rosenbrock, H., Ditter, M., Knoth, R. & Volk, B. Predominantly neuronal expression of cytochrome P450 isoforms CYP3A11 and CYP3A13 in mouse brain. Neuroscience 117, 521-529 (2003).
57. Bengtsson, S. K., Johansson, M., Backstrom, T. & Wang, M. Chronic allopregnanolone treatment accelerates Alzheimer's disease development in AbetaPP(Swe)PSEN1(DeltaE9) mice. J. Alzheimers Dis. 31, 71-84 (2012).
58. Zampieri, S. et al. Oxidative stress in NPC1 deficient cells: protective effect of allopregnanolone. J. Cell. Mol. Med. 13, 3786-3796 (2009).
59. He, J., Hoffman, S. W. & Stein, D. G. Allopregnanolone, a progesterone metabolite, enhances behavioral recovery and decreases neuronal loss after traumatic brain injury. Restor. Neurol. Neurosci. 22, 19-31 (2004).
60. Noorbakhsh, F. et al. Impaired neurosteroid synthesis in multiple sclerosis. Brain 134, 2703-2721 (2011).
61. Griffin, L. D., Gong, W., Verot, L. & Mellon, S. H. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat. Med. 10, 704-711 (2004).
62. Adeosun, S. O. et al. Allopregnanolone reinstates tyrosine hydroxylase immunoreactive neurons and motor performance in an MPTP-lesioned mouse model of Parkinson's disease. PLoS ONE 7, e50040 (2012).
63. Gee, K. W., Bolger, M. B., Brinton, R. E., Coirini, H. & McEwen, B. S. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action. J. Pharmacol. Exp. Ther. 246, 803-812 (1988).
64. Reddy, D. S. & Rogawski, M. A. Neurosteroid replacement therapy for catamenial epilepsy. Neurotherapeutics 6, 392-401 (2009).
65. Belelli, D. & Lambert, J. J. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat. Rev. Neurosci. 6, 565-575 (2005).
66. Kask, K., Backstrom, T., Nilsson, L. G. & Sundstrom-Poromaa, I. Allopregnanolone impairs episodic memory in healthy women. Psychopharmacology (Berl) 199, 161-168 (2008).
67. ClinicalTrials.gov. Allopregnanolone for the Treatment of Traumatic Brain Injury [online], http://clinicaltrials.gov/ct2/show/NCT016738 28?term=traumatic+brain+injury+and+allopregn anolone&rank=1 (2012).
68. Sperling, R. et al. Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 11, 241-249 (2012).
69. Sperling, R. A. et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimer's Dement. 7, 367-385 (2011).
70. Alzheimer Research Forum. CTAD: New Data on Sola, Bapi, Spark Theragnostics Debate [online], http://www.alzforum.org/new/detail. asp?id=3313 (2012).
71. Alzheimer Research Forum. Phase 3 Solanezumab Trials "Fail"-Is There a Silver Lining? [online], http://www.alzforum.org/new/detail.asp?id=3254 (2012).
72. Alzheimer Research Forum. Drugs In Clinical Trials [online], http://www.alzforum.org/drg/drc/detail.asp?id=108 (2012).
73. Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313-1317 (1998).
74. Hosie, A. M., Wilkins, M. E., da Silva, H. M. & Smart, T. G. Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature 444, 486-489 (2006).
75. Wang, J. M. & Brinton, R. D. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential. BMC Neurosci. 9 (Suppl 2), 2-11 (2008).
76. Manganas, L. N. et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318, 980-985 (2007).
77. Pereira, A. C. et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc. Natl. Acad. Sci. USA 104, 5638-5643 (2007).
78. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3-26 (2001).