Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Neuroprotective and Preventative Effects of Molecular Hydrogen

Author(s): Mami Noda*, Jiankang Liu and Jiangang Long

Volume 27, Issue 5, 2021

Published on: 19 October, 2020

Page: [585 - 591] Pages: 7

DOI: 10.2174/1381612826666201019103020

Price: $65

Abstract

One of the beneficial effects of molecular hydrogen (H2, hydrogen gas) is neuroprotection and prevention of neurological disorders. It is important and useful if taking H2 every day can prevent or ameliorate the progression of neurodegenerative disorders, such as Parkinson’s disease or Alzheimer’s disease, both lacking specific therapeutic drugs. There are several mechanisms of how H2 protects neuronal damage. Anti-oxidative, anti-inflammatory, and the regulation of the endocrine system via stomach-brain connection seem to play an important role. At the cellular and tissue level, H2 appears to prevent the production of reactive oxygen species (ROS), and not only hydroxy radical (•OH) but also superoxide. In Parkinson’s disease model mice, chronic intake of H2 causes the release of ghrelin from the stomach. In Alzheimer’s disease model mice, sex-different neuroprotection is observed by chronic intake of H2. In female mice, declines of estrogen and estrogen receptor-β (ERβ) are prevented by H2, upregulating brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB). The question of how drinking H2 upregulates the release of ghrelin or attenuates the decline of estrogen remains to be investigated and the mechanism of how H2 modulates endocrine systems and the fundamental question of what or where is the target of H2 needs to be elucidated for a better understanding of the effects of H2.

Keywords: Hydrogen gas, anti-oxidant, neuroprotection, ghrelin, estrogen, sex-difference.

« Previous Next »
[1]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[http://dx.doi.org/10.1038/nm1577] [PMID: 17486089]
[2]
Matchett GA, Fathali N, Hasegawa Y, et al. Hydrogen gas is ineffective in moderate and severe neonatal hypoxia-ischemia rat models. Brain Res 2009; 1259: 90-7.
[http://dx.doi.org/10.1016/j.brainres.2008.12.066] [PMID: 19168038]
[3]
Nishimaki K, Asada T, Ohsawa I, et al. Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Curr Alzheimer Res 2018; 15(5): 482-92.
[http://dx.doi.org/10.2174/1567205014666171106145017] [PMID: 29110615]
[4]
Ito M, Hirayama M, Yamai K, et al. Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats. Med Gas Res 2012; 2(1): 15.
[http://dx.doi.org/10.1186/2045-9912-2-15] [PMID: 22608009]
[5]
Dohi K, Kraemer BC, Erickson MA, et al. Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLoS One 2014; 9(9): e108034.
[http://dx.doi.org/10.1371/journal.pone.0108034] [PMID: 25251220]
[6]
Ono H, Nishijima Y, Ohta S, et al. Hydrogen gas inhalation treatment in acute cerebral infarction: a randomized controlled clinical study on safety and neuroprotection. J Stroke Cerebrovasc Dis 2017; 26(11): 2587-94.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.012] [PMID: 28669654]
[7]
Fu Y, Ito M, Fujita Y, et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neurosci Lett 2009; 453(2): 81-5.
[http://dx.doi.org/10.1016/j.neulet.2009.02.016] [PMID: 19356598]
[8]
Fujita K, Seike T, Yutsudo N, et al. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One 2009; 4(9): e7247.
[http://dx.doi.org/10.1371/journal.pone.0007247] [PMID: 19789628]
[9]
Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Sci Rep 2013; 3: 3273.
[http://dx.doi.org/10.1038/srep03273] [PMID: 24253616]
[10]
Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology 2009; 34(2): 501-8.
[http://dx.doi.org/10.1038/npp.2008.95] [PMID: 18563058]
[11]
Ohta S. Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochim Biophys Acta 2012; 1820(5): 586-94.
[http://dx.doi.org/10.1016/j.bbagen.2011.05.006] [PMID: 21621588]
[12]
Kalivendi SV, Kotamraju S, Cunningham S, Shang T, Hillard CJ, Kalyanaraman B. 1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide. Biochem J 2003; 371(Pt 1): 151-64.
[http://dx.doi.org/10.1042/bj20021525] [PMID: 12523938]
[13]
Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid Med Cell Longev 2012; 2012: 353152.
[http://dx.doi.org/10.1155/2012/353152] [PMID: 22720117]
[14]
Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev 2011; 91(2): 461-553.
[http://dx.doi.org/10.1152/physrev.00011.2010] [PMID: 21527731]
[15]
Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 2009; 29(13): 3974-80.
[http://dx.doi.org/10.1523/JNEUROSCI.4363-08.2009] [PMID: 19339593]
[16]
Wake H, Moorhouse AJ, Miyamoto A, Nabekura J. Microglia: actively surveying and shaping neuronal circuit structure and function. Trends Neurosci 2013; 36(4): 209-17.
[http://dx.doi.org/10.1016/j.tins.2012.11.007] [PMID: 23260014]
[17]
Kettenmann H, Kirchhoff F, Verkhratsky A. Microglia: new roles for the synaptic stripper. Neuron 2013; 77(1): 10-8.
[http://dx.doi.org/10.1016/j.neuron.2012.12.023] [PMID: 23312512]
[18]
Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci 2011; 31(45): 16064-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4158-11.2011] [PMID: 22072657]
[19]
Montero-Menei CN, Sindji L, Garcion E, et al. Early events of the inflammatory reaction induced in rat brain by lipopolysaccharide intracerebral injection: relative contribution of peripheral monocytes and activated microglia. Brain Res 1996; 724(1): 55-66.
[http://dx.doi.org/10.1016/0006-8993(96)00268-5] [PMID: 8816256]
[20]
Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10(11): 1387-94.
[http://dx.doi.org/10.1038/nn1997] [PMID: 17965659]
[21]
Imai K, Kotani T, Tsuda H, et al. Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia. Free Radic Biol Med 2016; 91: 154-63.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.015] [PMID: 26709014]
[22]
Zhuang X, Yu Y, Jiang Y, et al. Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway. Int Immunopharmacol 2020; 81: 106287.
[http://dx.doi.org/10.1016/j.intimp.2020.106287] [PMID: 32058932]
[23]
Chen H, Zhou C, Xie K, Meng X, Wang Y, Yu Y. Hydrogen-rich saline alleviated the hyperpathia and microglia activation via autophagy mediated inflammasome inactivation in neuropathic pain rats. Neuroscience 2019; 421: 17-30.
[http://dx.doi.org/10.1016/j.neuroscience.2019.10.046] [PMID: 31689487]
[24]
Zhang QS, Heng Y, Yuan YH, Chen NH. Pathological α-synuclein exacerbates the progression of Parkinson’s disease through microglial activation. Toxicol Lett 2017; 265: 30-7.
[http://dx.doi.org/10.1016/j.toxlet.2016.11.002] [PMID: 27865851]
[25]
Chien CH, Lee MJ, Liou HC, Liou HH, Fu WM. Microglia-derived cytokines/chemokines are involved in the enhancement of lps-induced loss of nigrostriatal dopaminergic neurons in dj-1 knockout mice. PLoS One 2016; 11(3): e0151569.
[http://dx.doi.org/10.1371/journal.pone.0151569] [PMID: 26982707]
[26]
Martin HL, Santoro M, Mustafa S, Riedel G, Forrester JV, Teismann P. Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson’s disease. Glia 2016; 64(3): 386-95.
[http://dx.doi.org/10.1002/glia.22935] [PMID: 26511587]
[27]
Barcia C, Ros CM, Annese V, et al. IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death Dis 2011; 2: e142.
[http://dx.doi.org/10.1038/cddis.2011.17] [PMID: 21472005]
[28]
Ouchi Y, Yoshikawa E, Sekine Y, et al. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 2005; 57(2): 168-75.
[http://dx.doi.org/10.1002/ana.20338] [PMID: 15668962]
[29]
Noda M, Fujita K, Ohsawa I, et al. Multiple effects of molecular hydrogen and its distinct mechanism. J Neurol Disord 2014; 2: 6.
[30]
Hirayama M, Ito M, Minato T, Yoritaka A, LeBaron TW, Ohno K. Inhalation of hydrogen gas elevates urinary 8-hydroxy-2′-deoxyguanine in Parkinson’s disease. Med Gas Res 2019; 8(4): 144-9.
[PMID: 30713666]
[31]
Murakami Y, Ito M, Ohsawa I. Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis. PLoS One 2017; 12(5): e0176992.
[http://dx.doi.org/10.1371/journal.pone.0176992] [PMID: 28467497]
[32]
Zhao TJ, Sakata I, Li RL, et al. Ghrelin secretion stimulated by beta1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice. Proc Natl Acad Sci USA 2010; 107(36): 15868-73.
[http://dx.doi.org/10.1073/pnas.1011116107] [PMID: 20713709]
[33]
Gagnon J, Anini Y. Insulin and norepinephrine regulate ghrelin secretion from a rat primary stomach cell culture. Endocrinology 2012; 153(8): 3646-56.
[http://dx.doi.org/10.1210/en.2012-1040] [PMID: 22691550]
[34]
Banks WA, Tschöp M, Robinson SM, Heiman ML. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 2002; 302(2): 822-7.
[http://dx.doi.org/10.1124/jpet.102.034827] [PMID: 12130749]
[35]
Zigman JM, Jones JE, Lee CE, Saper CB, Elmquist JK. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol 2006; 494(3): 528-48.
[http://dx.doi.org/10.1002/cne.20823] [PMID: 16320257]
[36]
Jiang H, Li LJ, Wang J, Xie JX. Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra. Exp Neurol 2008; 212(2): 532-7.
[http://dx.doi.org/10.1016/j.expneurol.2008.05.006] [PMID: 18577498]
[37]
Dong J, Song N, Xie J, Jiang H. Ghrelin antagonized 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in MES23.5 cells. J Mol Neurosci 2009; 37(2): 182-9.
[http://dx.doi.org/10.1007/s12031-008-9162-7] [PMID: 19052922]
[38]
Andrews ZB, Erion D, Beiler R, et al. Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. J Neurosci 2009; 29(45): 14057-65.
[http://dx.doi.org/10.1523/JNEUROSCI.3890-09.2009] [PMID: 19906954]
[39]
Elabi OF, Duskova K, Davies JS, Lane EL. The impact of ghrelin on the survival and efficacy of dopaminergic fetal grafts in the 6-ohda-lesioned rat. Neuroscience 2018; 395: 13-21.
[http://dx.doi.org/10.1016/j.neuroscience.2018.10.045] [PMID: 30414880]
[40]
Yoshii Y, Inoue T, Uemura Y, et al. Complexity of stomach-Brain Interaction Induced by Molecular Hydrogen in Parkinson’s Disease Model Mice. Neurochem Res 2017; 42(9): 2658-65.
[http://dx.doi.org/10.1007/s11064-017-2281-1] [PMID: 28462451]
[41]
Andrews ZB, Liu ZW, Walllingford N, et al. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008; 454(7206): 846-51.
[http://dx.doi.org/10.1038/nature07181] [PMID: 18668043]
[42]
Noda M, Ohsawa I, Ito M, et al. Beneficial effects of hydrogen in the CNS and a new brain-stomach interaction. Eur J Neurodegener Dis 2014; 3: 25-34.
[43]
Berthoud HR. Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol Motil 2008; 20(Suppl. 1): 64-72.
[http://dx.doi.org/10.1111/j.1365-2982.2008.01104.x] [PMID: 18402643]
[44]
Noda M, Uemura Y, Yoshii Y, et al. Circulating messenger for neuroprotection induced by molecular hydrogen. Can J Physiol Pharmacol 2019; 97(10): 909-15.
[http://dx.doi.org/10.1139/cjpp-2019-0098] [PMID: 31100203]
[45]
Lawrence CB, Snape AC, Baudoin FM, Luckman SM. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 2002; 143(1): 155-62.
[http://dx.doi.org/10.1210/endo.143.1.8561] [PMID: 11751604]
[46]
Asakawa A, Inui A, Kaga T, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 2001; 120(2): 337-45.
[http://dx.doi.org/10.1053/gast.2001.22158] [PMID: 11159873]
[47]
Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407(6806): 908-13.
[http://dx.doi.org/10.1038/35038090] [PMID: 11057670]
[48]
Bayliss JA, Andrews ZB. Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection. Ther Adv Endocrinol Metab 2013; 4(1): 25-36.
[http://dx.doi.org/10.1177/2042018813479645] [PMID: 23515333]
[49]
Frago LM. JA Chowen Involvement of Astrocytes in Mediating the Central Effects of Ghrelin. Int J Mol Sci 2017.
[50]
Shintani M, Ogawa Y, Ebihara K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001; 50(2): 227-32.
[http://dx.doi.org/10.2337/diabetes.50.2.227] [PMID: 11272130]
[51]
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402(6762): 656-60.
[http://dx.doi.org/10.1038/45230] [PMID: 10604470]
[52]
Ferrini F, Salio C, Lossi L, Merighi A. Ghrelin in central neurons. Curr Neuropharmacol 2009; 7(1): 37-49.
[http://dx.doi.org/10.2174/157015909787602779] [PMID: 19721816]
[53]
Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141(11): 4325-8.
[http://dx.doi.org/10.1210/endo.141.11.7873] [PMID: 11089570]
[54]
Nagaya N, Kojima M, Uematsu M, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 2001; 280(5): R1483-7.
[http://dx.doi.org/10.1152/ajpregu.2001.280.5.R1483] [PMID: 11294772]
[55]
Nagaya N, Miyatake K, Uematsu M, et al. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 2001; 86(12): 5854-9.
[http://dx.doi.org/10.1210/jcem.86.12.8115] [PMID: 11739451]
[56]
Frago LM, Baquedano E, Argente J, Chowen JA. Neuroprotective actions of ghrelin and growth hormone secretagogues. Front Mol Neurosci 2011; 4: 23.
[http://dx.doi.org/10.3389/fnmol.2011.00023] [PMID: 21994488]
[57]
Hwang S, Moon M, Kim S, Hwang L, Ahn KJ, Park S. Neuroprotective effect of ghrelin is associated with decreased expression of prostate apoptosis response-4. Endocr J 2009; 56(4): 609-17.
[http://dx.doi.org/10.1507/endocrj.K09E-072] [PMID: 19352052]
[58]
Kenny R, Cai G, Bayliss JA, et al. Endogenous ghrelin’s role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke? Am J Physiol Regul Integr Comp Physiol 2013; 304(11): R980-90.
[http://dx.doi.org/10.1152/ajpregu.00594.2012] [PMID: 23576609]
[59]
Spencer SJ, Miller AA, Andrews ZB. The role of ghrelin in neuroprotection after ischemic brain injury. Brain Sci 2013; 3(1): 344-59.
[http://dx.doi.org/10.3390/brainsci3010344] [PMID: 24961317]
[60]
Erşahin M, Toklu HZ, Erzik C, et al. The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. J Neurotrauma 2010; 27(6): 1143-55.
[http://dx.doi.org/10.1089/neu.2009.1210] [PMID: 20205513]
[61]
Cheng Y, Chen B, Xie W, et al. Ghrelin attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway in mice. Int Immunopharmacol 2020; 79: 106180.
[http://dx.doi.org/10.1016/j.intimp.2019.106180] [PMID: 31926478]
[62]
Chung H, Chung HY, Bae CW, Kim CJ, Park S. Ghrelin suppresses tunicamycin- or thapsigargin-triggered endoplasmic reticulum stress-mediated apoptosis in primary cultured rat cortical neuronal cells. Endocr J 2011; 58(5): 409-20.
[http://dx.doi.org/10.1507/endocrj.K10E-396] [PMID: 21490406]
[63]
Lim E, Lee S, Li E, Kim Y, Park S. Ghrelin protects spinal cord motoneurons against chronic glutamate-induced excitotoxicity via ERK1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β pathways. Exp Neurol 2011; 230(1): 114-22.
[http://dx.doi.org/10.1016/j.expneurol.2011.04.003] [PMID: 21530509]
[64]
Gahete MD, Córdoba-Chacón J, Kineman RD, Luque RM, Castaño JP. Role of ghrelin system in neuroprotection and cognitive functions: implications in Alzheimer’s disease. Peptides 2011; 32(11): 2225-8.
[http://dx.doi.org/10.1016/j.peptides.2011.09.019] [PMID: 21983104]
[65]
Eslami M, Sadeghi B, Goshadrou F. Chronic ghrelin administration restores hippocampal long-term potentiation and ameliorates memory impairment in rat model of Alzheimer’s disease. Hippocampus 2018; 28(10): 724-34.
[http://dx.doi.org/10.1002/hipo.23002] [PMID: 30009391]
[66]
Goshadrou F, Arefi Oskouie A, Eslami M, Nobakht Mothlagh Ghoochani BF. Effect of ghrelin on serum metabolites in Alzheimer’s disease model rats; a metabolomics studies based on 1H-NMR technique. Iran J Basic Med Sci 2018; 21(12): 1245-54.
[PMID: 30627368]
[67]
Stoyanova, II Ghrelin: a link between ageing, metabolism and neurodegenerative disorders. Neurobiol Dis 2014; 72(A): 72-83.
[68]
Can N, Catak O, Turgut B, et al. Neuroprotective and antioxidant effects of ghrelin in an experimental glaucoma model. Drug Des Devel Ther 2015; 9: 2819-29.
[PMID: 26082612]
[69]
Hou C, Peng Y, Qin C, Fan F, Liu J, Long J. Hydrogen-rich water improves cognitive impairment gender-dependently in APP/PS1 mice without affecting Aβ clearance. Free Radic Res 2018; 52(11-12): 1311-22.
[http://dx.doi.org/10.1080/10715762.2018.1460749] [PMID: 29683360]
[70]
Li J, Wang C, Zhang JH, Cai JM, Cao YP, Sun XJ. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res 2010; 1328: 152-61.
[http://dx.doi.org/10.1016/j.brainres.2010.02.046] [PMID: 20171955]
[71]
Wang C, Li J, Liu Q, et al. Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer’s disease. Neurosci Lett 2011; 491(2): 127-32.
[http://dx.doi.org/10.1016/j.neulet.2011.01.022] [PMID: 21238541]
[72]
Barnes LL, Wilson RS, Bienias JL, Schneider JA, Evans DA, Bennett DA. Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry 2005; 62(6): 685-91.
[http://dx.doi.org/10.1001/archpsyc.62.6.685] [PMID: 15939846]
[73]
Shumaker SA, Legault C, Rapp SR, et al. WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289(20): 2651-62.
[http://dx.doi.org/10.1001/jama.289.20.2651] [PMID: 12771112]
[74]
Fitzpatrick JL, Mize AL, Wade CB, Harris JA, Shapiro RA, Dorsa DM. Estrogen-mediated neuroprotection against beta-amyloid toxicity requires expression of estrogen receptor alpha or beta and activation of the MAPK pathway. J Neurochem 2002; 82(3): 674-82.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01000.x] [PMID: 12153491]
[75]
Cordey M, Gundimeda U, Gopalakrishna R, Pike CJ. Estrogen activates protein kinase C in neurons: role in neuroprotection. J Neurochem 2003; 84(6): 1340-8.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01631.x] [PMID: 12614334]
[76]
Long J, He P, Shen Y, Li R. New evidence of mitochondria dysfunction in the female Alzheimer’s disease brain: deficiency of estrogen receptor-β. J Alzheimers Dis 2012; 30(3): 545-58.
[http://dx.doi.org/10.3233/JAD-2012-120283] [PMID: 22451324]
[77]
Nagahara AH, Merrill DA, Coppola G, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 2009; 15(3): 331-7.
[http://dx.doi.org/10.1038/nm.1912] [PMID: 19198615]
[78]
Morale MC, Serra PA, L’episcopo F, et al. Estrogen, neuroinflammation and neuroprotection in Parkinson’s disease: glia dictates resistance versus vulnerability to neurodegeneration. Neuroscience 2006; 138(3): 869-78.
[http://dx.doi.org/10.1016/j.neuroscience.2005.07.060] [PMID: 16337092]
[79]
Valles SL, Dolz-Gaiton P, Gambini J, et al. Estradiol or genistein prevent Alzheimer’s disease-associated inflammation correlating with an increase PPAR gamma expression in cultured astrocytes. Brain Res 2010; 1312: 138-44.
[http://dx.doi.org/10.1016/j.brainres.2009.11.044] [PMID: 19948157]
[80]
Stievenard A, Méquinion M, Andrews ZB, et al. Is there a role for ghrelin in central dopaminergic systems? Focus on nigrostriatal and mesocorticolimbic pathways. Neurosci Biobehav Rev 2017; 73: 255-75.
[http://dx.doi.org/10.1016/j.neubiorev.2016.11.021] [PMID: 27914942]

Rights & Permissions Print Cite
Article Metrics
31
© 2024 Bentham Science Publishers | Privacy Policy