The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression
American Journal of Psychiatry and Neuroscience
Volume 3, Issue 5, September 2015, Pages: 77-89
Received: Jul. 9, 2015; Accepted: Jul. 27, 2015; Published: Aug. 3, 2015
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John W. Wright, Departments of Psychology, Integrative Physiology and Neuroscience, and Program in Biotechnology, Washington State University, Pullman, USA; M3 Biotechnology, Inc., Seattle, USA
Joseph W. Harding, Departments of Psychology, Integrative Physiology and Neuroscience, and Program in Biotechnology, Washington State University, Pullman, USA; M3 Biotechnology, Inc., Seattle, USA
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Major depression is a common form of mental disorder affecting approximately 15% of the population at least once during lifetime. The etiology of depression is complex with potential contributions from central and peripheral systemic factors, and several CNS impacting diseases. Presently employed antidepressant medications are poorly responded to by upwards of 50% of patients and typically require weeks of treatment to be effective. Recent post-mortem brain scans indicate significant volume reductions in two limbic brain structures, the hippocampus and prefrontal cortex of depressed patients. These findings focus attention on hippocampal plasticity in the neuropathology of depression and the possible dysfunction of several important processes including neurogenesis, synaptogenesis, and contributions by neurotrophic growth factors. The hepatocyte growth factor (HGF)/c-Met receptor system is a powerful mediator of synaptogenesis and neurogenesis, and if adequately activated may serve to counter the neuropathology of depression. The brain renin-angiotensin system (RAS) interacts with the HGF/c-Met system and plays a major role in responding to stress and the pathophysiology of depression. We have developed an angiotensin IV-based small molecule designed to activate the HGF/c-Met receptor system in order to provide neuroprotection, synaptogenesis, and neurogenesis in the hippocampus and prefrontal cortex. This analog may be efficacious in treating the neuropathology of depression.
Depression, Angiotensin II, Angiotensin IV, AT4 Receptor, Hepatocyte Growth Factor, C-Met Receptor, Dihexa
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John W. Wright, Joseph W. Harding, The Development of Small Molecule Angiotensin IV-Based Analogs to Treat Depression, American Journal of Psychiatry and Neuroscience. Vol. 3, No. 5, 2015, pp. 77-89. doi: 10.11648/j.ajpn.20150305.11
R.C. Kessler, P. Berglund, O. Demler, R. Jin, D. Koretz, K.R. Merikangas, A.J. Rush, E.E. Walters, and P.S. Wang, “The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R),” JAMA, vol. 289, no. 23, pp. 3095-105, 2003.
R.C. Kessler, S. Avenevoli, and K. Merikangas, “Mood disorders in children and adolescents: An epidemiologic perspective,” Biol Psychiatry, vol. 49, no.12, pp. 1002-14, 2001.
E. Dozeman, H.W. van Marwijk, D.J. van Schaik, M.L. Stek, H.E. van der Horst, A.T. Beekman, and H.P. van Houl, “High incidence of clinically relevant depressive symptoms in vulnerable persons of 75 years or older living in the community,” Aging Ment Health, vol. 14, no. 7, pp. 828-833, 2010.
T.W. Meeks, I.V. Vahia, H. Lavretsky, and D.V. Jesle, “A tune in “a minor” can “b major”: A review of epidemiology, illness course, and public health implications of subthreshold depression in older adults,” J Affect Disord, vol. 129, no. 1-3, pp. 126-42, 2010.
S.M. Thielke, P. Diehr, and J. Unutzer, “Prevalence, incidence, and persistence of major depressive symptoms in the Cardiovascular Health Study,” Aging and Mental Health, vol. 14, no. 7, pp. 168-176, 2010.
S. Aznar and G.M. Knudsen, “Depression and Alzheimer’s disease: Is stress the initiating factor in a common neuropathological cascade?” J Alzheimers Dis, vol. 23, no. 2, pp. 177-93, 2011.
J. Fang and Q. Cheng, “Etiological mechanisms of post-stroke depression: A review,” Neurol Res, vol. 31, no. 9, pp. 904-9, 2009.
M.C. Rodriguez-Oroz, M. Jahanshahi, P. Krack, I. Litvan, R. Macias, E. Bezard, and J.A. Obeso, “Initial clinical manifestations of Parkinson’s disease: Features and pathophysiological mechanisms,” Lancet Neurol, vol. 8, no. 12, pp. 1128-39, 2009.
M.A. Bremmer, A.T. Beekman, D.J. Deeg, B.W. Penninx, M.G. Dik, C.E. Hack, and W.J. Hoogendijk, “Inflammatory markers in late-life depression: Results from a population-based study,” J Affect Disord, vol. 106, no. 3, pp. 249-55, 2008.
L. Flicker, “Cardiovascular risk factors, cerebrovascular disease burden, and healthy brain aging,” Clin Geriatr Med, vol. 26, no. 1, p. 17-27, 2010.
S.E. Arnold, S.X. Xie, Y.Y. Leung, L.S. Wang, M.A. Kling, X. Han, E.J. Kim, D.A. Wojk, D.A. Bennett, A. Chen-Plotkin, M. Grossman, W. Hu, V.M. Lee, R.S. Mackin, J.Q. Trojanowski, R.S. Wilson, and L.M. Shaw, “Plasma biomarkers of depressive symptoms in older adults,” Transl Psychiatry, vol. 2, Article ID e65,10.1038/tp.2011.63, 2012.
M.A. Bremmer, D.J. Deeg, A.T. Beekman, B.W. Pelnnix, P. Lips, and W.J. Hoogendijk, “Major depression in late life is associated with both hypo-and hypercortisolemia,” Biol Psychiatry, vol. 62, no. 5, pp. 479-86, 2007.
L. Amato, G. Paolisso, F. Cacciatore, N. Ferrara, S. Canonico, F. Grengo, and M. Verricchio, “Non-insulin-dependent diabetes mellitus is associated with a greater prevalence of depression in the elderly. The Osservatorio Geriatrico of Campania Region Group,” Diabetes Metab, vol. 22, no. 5, pp. 314-8, 1996.
K.S. Lee, J.H. Chung, K.H. Lee, M.J. Shin, B.H. Oh, S.H. Lee, and C.H. Hong, “Simultaneous measurement of 23 plasma cytokines in late-life depression,” Neurol Sci, vol. 30, no. 5, pp. 435-8, 2009.
B.S. Diniz, A.L. Teixeira, L.L. Talib, V.A. Mendonca, W.F. Gattaz, and O.V. Forlenza, “Serum brain-derived neurotrophic factor level is reduced in antidepressant-free patients with late-life depression,” World J Biol Psychiatry, vol. 11, no. 3, pp. 550-5, 2010.
N. Ho, M.S. Sommers, and I. Lucki, “Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression,” Neurosci Biobehav Rev, vol. 37, no. 8, pp. 1346-62, 2013.
W. Katon, H.S. Pedersen, and A.R. Ribe, “Effect of depression and diabetes mellitus on the risk for Dementia: A national population-based cohort study,” JAMA Psychiatry, vol. 72, no. 6, pp. 612-9, 2015.
M.J. Stuart and B.T. Baune, “Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neurosci Biobehav Rev, vol. 36, no. 1, pp. 658-76, 2012.
J. Mill and A. Petronis, “Molecular studies of major depressive disorder: The epigenetic perspective,” Mol Psychiatry, vol. 12, no. 9, pp. 799-814, 2007.
W. Drevets, J.L. Price, and M.L. Furey, “Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression,” Brain Struct Funct, vol. 213, no. 1-2, pp. 93-118, 2008.
J. Miguel, H. Hidalgo, and G. Rajkowska, “Morphological brain changes in depression: Can antidepressants reverse them,” CNS Drugs, vol. 16, no. 6, pp. 361-72, 2002.
R. Duman and L.M. Monteggia, “A neurotrophic model for stress-related mood disorders,” Biol Psychiatry, vo. 59, no. 12, pp. 1116-27, 2006.
V. Krishnan and E.J. Nestler, “The molecular neurobiology of depression,” Nature, vol. 455, no. 7215, pp. 894-902, 2008.
I. Amrein, K. Isler, and H.P. Lipp, “Comparing adult hippocampal neurogenesis in mammalian species and orders: Influence of chronological age and life history stage,” Eur J Neurosci, vol. 34, no. 6, pp. 978-87, 2011.
R.S. Duman and N. Li, “A neurotrophic hypothesis of depression: Role of synaptogenesis in the actions of NMDA receptor antagonists,” Philos Trans R Soc Lond B Biol Sci, vol. 367, no. 1601, pp. 2475-84, 2012.
E. Drapeau and D.N. Abrous, “Stem cell review series: Role of neurogenesis in age-related memory disorders,” Aging Cell, vol. 7, no. 4, pp. 569-89, 2008.
C.J. Miranda, L. Braun, Y. Jiang, M.E. Hesler, L. Zhang, M. Riolo, H. Wang, M. Rao, R.A. Altura, and B.K. Kaspar, “Aging brain microenvironment decreases hippocampal neurogenesis through Wnt-mediated surviving signaling,” Aging Cell, vol. 11, no. 3, pp. 542-52, 2012.
M. Boldrini, M.D. Underwood, R. Hen, O.B. Rosoklia, A.J. Dwork, J. John Mann, and V. Arango, “Antidepressants increase neural progenitor cells in the human hippocampus,” Neuropsychopharmacology, vol. 34, no. 11, pp. 2376-89, 2009.
F. Calabrese, A.D. Rossetti, G. Racagni, P. Gass, M.A. Riva, and R. Molteni, “Brain-derived neurotrophic factor: A bridge between inflammation and neuroplasticity,” Front Cell Neurosci, vol. 8, no. 430, pp. 1-7, 2014.
N.M. Fournier and R.S. Duman, “Role of vascular endothelial growth factor in adult hippocampal neurogenesis: Implications for the pathophysiology and treatment of depression,” Behav Brain Res, vol. 227, no. 2, pp. 440-9, 2011.
S. Hayley and D. Litteljohn, “Neuroplasticity and the next wave of antidepressant strategies,” Front Cell Neurosci, vol. 7, no. 218, pp. 1-17, 2013.
G. Masi and P. Brovedani, “The hippocampus, neurotrophic factors and depression: Possible implications for the pharmacotherapy of depression, CNS Drugs, vol. 25, no. 11, pp. 913-31, 2011.
E. Castren and T. Rantamaki, “The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity,” Dev Neurobiol, vol. 70, no. 5, pp. 289-97, 2010.
S. Heldt, L. Stanek, J.P. Chhatwal, and K.J. Ressler “Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories,” Mol Psychiatry, vol. 12, no. 7, pp. 656-70, 2007.
D. Taliz, N. Stall, D.E. Dar, and A. Zangen, “Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis,” Mol Psychiatry, vol. 15, no. 1, pp. 80-92, 2010.
J.W. Wright and J.W. Harding, “Brain renin-angiotensin – A new look at an old system,” Prog Neurobiol, vol. 95, no. 1, pp.49-67, 2011.
J. W. Wright and J.W. Harding, “The brain renin-angiotensin system: A diversity of functions and implications for CNS diseases,” Pflugers Arch – Eur J Physiol, vol. 465, no. 1, pp. 133-51, 2013.
F. Maina and R. Klein, “Hepatocyte growth factor, a versatile signal for developing neurons,” Nat Neurosci vol. 2, no. 3, pp. 213-7, 1999.
W. Sun, H. Funakoshi, and T. Nakamura, “Localization and functional role of hepatocyte growth factor (HGF) and its receptor c-met in the rat developing cerebral cortex,” Brain Res, Mol Brain Res, vol. 103, no. 1-2, pp. 36-48, 2002.
M. de Gasparo, K.J. Catt, T. Inagami, J.W. Wright, and T. Unger, “International Union of Pharmacology. XXIII. The angiotensin II receptors,” Pharmacol Rev, vol. 52. no. 3, pp. 415-72, 2000.
J.W. Wright and J.W. Harding, “Important roles for angiotensin III and IV in the brain renin-angiotensin system,” Brain Res Rev, vol. 25, no. 1, pp. 96-124, 1997.
A. Lippoldt, M. Paul, K. Fuxe, and D. Ganten, “The brain renin-angiotensin system: Molecular mechanisms of cell to cell interactions,” Clin Exper Hypertens vol. 17, no. 1-2, pp. 251-66, 1995.
M.I. Phillips, E.A. Speakman, and B. Kimura, “Levels of angiotensin and molecular biology of the tissue rennin angiotensin systems,” Regul Pept, vol. 43, no. 1-2, pp. 1-20, 1993.
J.M. Saavedra, “Brain and pituitary angiotensin,” Endocrinology Reviews, vol. 13, no. 2, pp. 329-380, 1992.
A. Dominguez-Meijide, B. Villar-Cheda, P. Garrido-Gil, G. Sierna-Paredes, M.J. Guerra, and J.L. Labandeira-Garcia, “Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson’s disease treated with L-DOPA,” Neuropharmacology, vol. 76(Pt A), pp. 156-68, 2014.
P.K. Sonsalla, C. Coleman, L.Y. Wong, S.L. Harris, J.R. Richardson, B.S. Gadad, W. Li, and D.C. German, “The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of Parkinsonism,” Exp Neurol, vol. 250, pp. 376-83, 2013.
J. Lu, L. Wu, T. Jiang, Y. Wang, H. Zhao, Q. Gao, Y. Pan, Y. Tian and Y. Zhang, “Angiotensin AT2 receptor stimulation inhibits activation of NADPH oxidase and ameliorates oxidative stress in rotenone model of Parkinson’s disease in CATH.a cells,” Neurotoxicol Teratol vol. 47, pp. 16-24, 2015.
J. Kunz, D. Krause, M. Kremer, and R. Dermietzel, “The 140-kDa protein of blood-brain barrier-associated pericytes is identical to aminopeptidase N,” J Neurochem, vol. 62, no. 6, pp. 2375-86, 1994.
E.A. Kramár, J.W. Harding, and J.W. Wright, “Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes,” Regul Pept, vol. 68, no. 2, pp. 131-8, 1997.
E.A. Kramár, R. Krishnan, J.W. Harding, J.W. Wright, “Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow,” Regul Pept, vol. 74, no. 2-3, pp. 185-92, 1998.
L. Naveri, C. Stromberg, and J.M. Saavedra, “Angiotensin IV reverses the acute cerebral blood flow reduction after experimental subarachnoid hemorrhage in the rat,” J Cereb Blood Flow Metab, vol. 14, no. 6, pp. 1096-9, 1994.
K. Lanckmans, B. Stragier, S. Sarre et al., “Nano-LC-MS/MS for the monitoring of angiotensin IV in rat brain microdialysates: Limitations and possibilities,” Journal of Separation Science, vol. 30, no. 14, pp. 2217-2224, 2007.
K. Lanckmans, S. Sarre, I. Smolders, Y. and Michotte, “Use of a structural analogue versus a stable isotope labeled internal standard for the quantification of angiotensin IV in rat brain dialysates using nano-liquid chromatography/tandem mass spectrometry,” Rapid Commun Mass Spectrom, vol. 21, no. 7, pp. 1187-95, 2007.
B. Stragier, D. De Bundel, S. Sarre, I. Smolders, G. Vauquelin, A. Dupont, Y. Michotte, and P. Vanderheyden, “Involvement of insulin-regulated aminopeptidase in the effects of the renin-angiotensin fragment angiotensin IV: A review,” Heart Fail Rev, vol. 13, no. 3, pp. 321-37, 2008.
P.C. Ma, G. Maulik, J. Christensen, and R. Salgia, “C-Met: Structure, functions and potential for therapeutic inhibition,” Cancer Metastasis Rev, vol. 22, no. 4, pp. 309-25, 2003.
T. Nakamura and S. Mizuno, “The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine,” Proc Jap Acad, Ser B Phys Biol Sci, vol. 86, no. 6, pp. 588-610, 2010.
D.P. Bottaro, J.S. Rubin, D.L. Faletto, A.M. Chan, T.E. Kmiecik, G.F. Vande Woude, and S.A. Aaronson, “Identification of the hepatocyte growth factor receptor as the c-met proto-ongogene product,” Science, vol. 251, no. 4995, pp. 802-4, 1991.
N. Shinomiya and G.F. Vande Woude, “Suppression of met expression: A possible cancer treatment,” Clin Cancer Res, vol. 9, no. 14, pp. 5085-90, 2003.
D. Tulasne and B. Foveau, “The shadow of death on the MET tyrosine kinase receptor,” Cell Death Diff, vol. 15, no. 3, pp. 427-34, 2008.
R. Zachow and M. Uzumeu, “The hepatocyte growth factor system as a regulator of female and male gonadal function,” J Endocrinol, vol. 195, no. 3, pp. 359-71, 2007.
W.G. Jiang, T.A. Martin, C. Parr, G. Davies, K. Matsumoto, and T. Nakamura, “Hepatocyte growth factor, its receptor, and their potential value in cancer therapies,” Crit Rev Oncol Hematol, vol. 53, no. 1, pp. 35-69, 2005.
M. Shimamura, N. Sato, S. Waguri, Y. Uchiyama, T. Hayashi, H. Iida, T. Nakamura, T. Ogihara, Y. Kaneda, and R. Morishta, “Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction,” Hypertension, vol. 47, no. 4, pp. 742-51, 2006.
M. Akimoto, A. Baba, Y. Ikeda-Matsuo, M.K. Yamada, R. Itamura, N. Nishiyama, Y. Ikegaya, and N. Matsuki, “Hepatocyte growth factor as an enhancer of NMDA currents and synaptic plasticity in the hippocampus,” Neuroscience, vol. 128, no. 1, pp. 155-62, 2004.
I. Date, N. Takagi, K. Takagi, T. Kago, K. Matsumoto, T. Nakamura, and S. Takeo, “Hepatocyte growth factor attenuates cerebral ischemia-induced learning dysfunction,” Biochem Biophys Res Commun, vol. 319, no. 4, pp. 1152-8, 2004.
S. Takeo, N. Takagi, and K. Takagi, “Ischemic brain injury and hepatocyte growth factor,” Yakugaku Zasshi, vol. 127, no. 11, pp. 1813-23, 2007.
S.K. Sharma, “Hepatocyte growth factor in synaptic plasticity and Alzheimer’s disease,” Sci World J, vol. 10, pp. 457-61, 2010.
J.W. Wright, L.H. Kawas, and J.W. Harding, “The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases,” Prog Neurobiol, vol. 125, pp. 26-46, 2015.
GJ. Martins, C. Plachez, and E.M. Powell, “Loss of embryonic MET signaling alters profiles of hippocampal interneurons,” Dev Neurosci, vol. 29, no. 1-2, pp. 143-58, 2007.
T. Miyazawa, K. Matsumoto, H. Ohmichi, H. Katoh, T. Yamashima, and T. Nakamura, “Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor: A novel neurotrophic factor,” J Cereb Blood Flow Metab, vol. 18, no. 4, pp. 345-8, 1998.
H. Funakoshi and T. Nakomura, “Hepatocyte growth factor (HGF): Neurotrophic functions and therapeutic implications for neuronal injury/diseases,” Curr Signal Transduct Theory, vol. 6, pp. 156-67, 2011.
M. Shimamura, N. Sato, and R. Morishita, “Experimental and clinical application of plasmid DNA in the field of central nervous diseases,” Curr Gene Ther, vol. 11, no. 6, pp. 491-500, 2011.
M. Hamanoue, N. Takemoto, K. Matsumoto, T. Nakamura, K. Nakajima and S. Kohsaka, “Neurotrophic effect of hepatocyte growth factor on central nervous system neurons in vitro,” J Neurosci Res, vol. 43, no. 5, pp. 554-64, 1996.
H. Koike, R. Morishita, S. Iguchi, M. Aokik, K. Matsumoto, C. Yokoyama, T. Tanabe, T. Ogihara and Y. Kaneda, “Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin synthase gene,” FASEB J, vol. 17, no. 6, pp. 779-81, 2003.
B.J. Yamamoto, P.D. Elias, J.A. Masino, B.D. Hudson, A.T. McCoy, Z.J. Anderson, M.D. Varnum, M.F. Sardinia, J.W. Wright, and J.W. Harding, “The angiotensin IV analog Nle-Tyr-Leu-psi-(CH2-NH2)3-4-His-Pro-Phe (norleual) can act as a hepatocyte growth factor/c-Met inhibitor,” J Pharmacol Exp Ther, vol. 333, no. 1, pp. 161-73, 2010.
L.H. Kawas, B.J. Yamamoto, J.W. Wright, J.W. Harding, “Mimics of the dimerization domain of hepatocyte growth factor exhibit anti-met and anticancer activity,” J Pharmacol Exp Ther, vol. 339, no. 2, pp. 509-18, 2011.
L.H. Kawas, A.T. McCoy, B.J. Yamamoto, J.W. Wright, and J.W. Harding, “Development of angiotensin IV analogs as hepatocyte growth factor/Met modifiers,” J Pharmacol Exp Ther, vol. 340, no. 3, pp. 539-48, 2012.
S.Y. Chai, M.A. Bastias, E.F. Clune, D.J. Matsacos, T. Mustafa, J.H. Lee, S.G. McDowall, G. Paxinos, F.A. Mendelsohn, and S.L. Albiston, “Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualized by in vitro receptor autoradiography,” J Chem Neuroanat, vol. 20, no. 3-4, pp. 339-48, 2000.
P.R. Gard, “The role of angiotensin II in cognition and behavior,” Eur J Pharmacol, vol. 438, no. 1-2, pp. 1-14, 2002.
J.W. Harding, V.I. Cook, A.V. Miller-Wing, H.M. Hanesworth, M.F. Sardinia, K.L. Hall, J.W. Stobb, G.N. Swanson, J.K. Coleman, and J.W. Wright, “Identification of an AII (3-8) [AIV] binding site in guinea pig hippocampus,” Brain Res, vol. 583, no. 1-2, pp. 340-3, 1992.
J.W. Wright, B.J. Yamamoto, and J.W. Harding, “Angiotensin receptor subtype mediated physiologies and behaviors: New discoveries and clinical targets,” Prog Neurobiol, vol. 84, no. 2, pp. 157-81, 2008.
A.T. McCoy, C.C. Benoist, J.W. Wright, L.H. Kawas, J.M. Bule-Ghogare, M. Zhu, S.M. Appleyard, G.A. Wayman, and J.W. Harding, “Evaluation of metabolically stabilized angiotensin IV analogs as pro-cognitive/anti-dementia agents,” J Pharmacol Exp Ther, vol. 344, no. 1, pp. 141-54, 2013.
S.J. Tyndall and R.S. Walikonis, “The receptor tyrosine kinase Met and its ligand hepatocyte growth factor are clustered at excitatory synapses and can enhance clustering of synaptic proteins,” Cell Cycle, vol. 5, no. 14, pp. 1560-8, 2006.
C.J. Davis, E.A. Kramar, A. De, P.C. Meighan, S.M. Simasko, J.W. Wright, and J.W. Harding, “AT4 receptor activation increases intracellular calcium influx and induces a non-N-methyl-D-aspartate dependent form of long-term potentiation,” Neuroscience, vol. 137, no. 4, pp. 1369-79, 2006.
S.J. Tyndall, S.J. Patel, and R.S. Walikonis, “Hepatocyte growth factor-induced enhancement of dendritic branching is blocked by inhibitors of N-methyl-D-aspartate receptors and calcium/calmodulin-dependent kinases,” J Neurosci Res, vol. 85, no. 11, pp. 2343-51, 2007.
B. Stragier, S. Sarre, P. Vanderheyden, G. Vauquelin, M.C. Fournie-Zaluski, G. Ebinger, and Y. Michotte, “Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat,” J Neurochem, vol. 90, no. 5, pp. 1251-7, 2004..
J. Lee, S.Y. Chai, F.A. Mendelsohn, M.J. Morris, A.M. Allen, “Potentiation of cholinergic transmission in the rat hippocampus by angiotensin IV and LVV-hemorphin-7,” Neuropharmacology, vol. 40, no. 4, pp. 618-23, 2001.
S.E. Meighan, P.C. Meighan, P. Choudhury, C.J. Davis, M.L. Olson, P.A. Zornes, J.W. Wright and J.W. Harding, “Effects of extracellular matrix-degrading proteases matrixmetalloproteinases 3 and 9 on spatial learning and synaptic plasticity,” J Neurochem, vol. 96, no. 5, pp. 1227-41, 2006.
P.D. Meighan, S.E. Meighan, C.J. Davis, J.W. Wright, and J.W. Harding, “Effects of matrix metalloproteinase inhibition on short- and long-term plasticity of schaffer collateral/CA1 synapses,” J Neurochem, vol. 102, no. 6, pp. 2085-96, 2007.
C.C. Benoist, J.W. Wright, M. Zhu, S.M. Appleyard, G.A. Wayman, and J.W. Harding, “Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogues,” J Pharmacol Exp Ther, vol. 339, no. 1, pp. 35-44, 2011.
P.W. Gold, F.K. Goodwin, and G.P. Chrousos, “Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (2),” N Engl J Med, vol. 319, no. 7, pp. 413-20, 1988.
J.E. LeDouz, “Emotion: Clues from the brain,” Annu Rev Psychol, vol. 46, no. 4, pp. 209-35, 1995.
P.W. Gold, “The neurobiology of stress and its relevance to psychotherapy,” Clin Neurosci Res, vol. 4, no. 5-6, pp. 315-24, 2005.
P.W. Gold and G.P. Chrousos, “Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/NE states,” Mol Psychiatry, vol. 7, no. 3, pp. 254-75, 2002.
P.W. Gold, R. Machado-Vieira, and M.G. Pavlatou, “Clinical and biochemical manifestations of depression: Relation to the neurobiology of stress,” Neural Plast, vol. 2015, Article ID 581976, 2015.
N. Bakunina, C.M. Pariante, and P.A. Zunszain, “Immune mechanisms linked to depression via oxidative stress and neuroprogression,” Immunology, vol. 144, no. 1, pp. 365-73, 2015.
V. Krishnan and E.J. Nestler, “The molecular neurobiology of depression,” Nature, vol. 455, no. 7215, pp. 894-902, 2008.
J.M. Saavedra and J. Benicky, “Brain and peripheral angiotensin II play a major role in stress. Stress, vol. 10, no. 2, pp. 185-93, 2007.
J. Rodriguez-Pallares, P. Rey, J.A. Parga, Z. Munoz, M.J. Guerra, and J.L. Labandeira-garcia, “Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS,” Neurobiol Dis, vol. 31, no. 1, pp. 58-73, 2008.
B.M. Babior, “NADPH oxidase,” Curr Opin Immunol, vol. 16, no. 1, pp. 42-7, 2004.
A. Okamura, H. Rakugi, M. Ohishi, Y. Yanagitani, S. Takiuchi, K. Monguchi, P.A. Fennesey, J. Higaki, and T. Ogihara, “Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages,” J Hypertens, vol. 17, no. 4, pp. 537-45, 1999.
J.M. Saavedra, “Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders,” Clin Sci (Lond), vol. 123, no.10, pp. 567-90, 2012.
S. Villapol and J.M. Saavedra, “Neuroprotective effects of angiotensin receptor blockers,” Am J Hypertens, vol. 28, no. 3, pp. 289-99, 2015..
T.N. Grammatopoulos, S.M. Jones, F.A. Ahmadi, B.R. Hoover, L.D. Snell, J. Skoch, V.V. Jhaven, A.M. Poczobutt, J.A. Weyhenmeyer, and W.M. Zawada, “Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra,” Mol Neurodegener, vol. 2, pp. 1-17, 2007.
P. Garrido-Gil, B. Joglar, A.I. Rodriguez-Perez, M.J. Guerra, and J.L. Labandeira-Garcia, “Involvement of PPAR-gamma in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: Effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson’s disease,” J Neuroinflammation, vol. 9, pp. 38-54, 2012.
P. Rey, A. Lopez-Real, S. Sanchez-Iglesias, A. Munoz, R. Soto-Otero, and J.L. Labandeira-Garcia, “Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons,” Neurobiol Aging, vol. 28, no. 4, pp. 555-67, 2007.
A. Munoz, P. Rey, and M.J. Guerra, “Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of Parkinsonism,” Neuropharmacology vol. 51, no. 1, pp. 112-20, 2006.
A. Lopez-Real, P. Rey, R. Soto-Otero, E. Mendez-Alvarez, and J.L. Labendeira-Garcia, “Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of parkinsonism,” J Neurosci Res, vol. 81, no. 6, pp. 865-73, 2005.
B. Mertens, P. Vanderheyden, Y. Michotte, and S. Sarre, “The role of the central renin-angiotensin system in Parkinson’s disease,” J Renin-Angiotensin Aldosterone Syst, vol. 11, no. 1, pp. 49-56, 2010.
E.F. Grady, L.A. Sechi, C.A. Griffin, M. Schambelan, and J.E. Kalinyak, “Expression of AT2 receptors in the developing rat fetus,” J Clin Invest, vol. 88, no. 3, pp. 921-33, 1991.
Z. Lenkei, M. Palkovits, M.P. Corvol, and C. Llorens-Cortes, “Distribution of angiotensin II type-2 receptor (AT2) mRNA expression in the adult rat brain,” J Comp Neurol, vol. 373, no. 3, pp. 322-39, 1996.
K. Song, A.M. Allen, G. Paxinos, and F.A. Mendelsohn, “Mapping of angiotensin II receptor subtype heterogeneity in rat brain,” J Comp Neurol vol. 16, no. 4, pp. 467-84, 1992.
A.M. Nuyt, Z. Lenkei, M. Palkovits, P. Corvol, and C. Llorens-Cortes, “Ontogeny of angiotensin II type 2 receptor mRNA expression in fetal and neonatal rat brain,” J Comp Neurol, vol. 407, no. 2, pp. 193-206, 1999.
S. Meffert, S.M. Stoll, U.M. Steckelings, S.P. Bottari, and T. Unger, “The angiotensin II AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells,” Mol Cell Endocrinol, vol. 122, no. 1, pp. 59-67, 1996.
J. Li, J. Culman, H. Hortnagl, Y. Zhao,k N. Oerova, M. Timm, A. Vlume, M. Zimmermann, K. Seidel, U. Dimagl, and T. Unger, “Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury,” FASEB J, vol. 19, no. 6, pp. 617-9, 2005
J. Rodriguez-Pallares, C.R. Quiroz, J.A. Parga, M.J. Guerra, and J.L. Labandeira-Garcia, “Angiotensin II increases differentiation of dopaminergic neurons from mesencephalic precursors via angiotensin type 2 receptors,” Eur J Neurosci, vol. 20, no. 6, pp. 1489-98, 2004.
H.Y. Sohn, U. Raff, A. Hoffmann, T. Gloe, K. Heermeier, J. Galle, and U. Pohl, “Differential role of angiotensin II receptor subtypes on endothelial superoxide formation,” Br J Pharmacol, vol. 131, no. 4, pp. 667-72, 2000.
J. Rodriguez-Pallares, P. Rey, J.A. Parga, A. Munoz, M.J. Guerra, J.L. Labandeira-Garcia, “Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS,” Neurobiol Dis, vol. 31, no. 1, pp. 58-73, 2008.
P.W. Gold, “The organization of the stress system and its dysregulation in depressive illness,” Mol Psychiatry, vol. 20, no. 1, pp. 32-47, 2015.
L. Naveri, C. Stromberg, and J.M. Saavedra, “Angiotensin IV reverses the acute cerebral blood flow reduction after experimental subarachnoid hemorrhage in the rat,” J Cereb Blood Flow Metab, vol. 14, no. 6, pp. 1096-9, 1994.
F. Dalmay, F. Pesteil, and J. Allard, “Angiotensin IV decreases acute stroke mortality in the gerbil,” Hypertens, vol. 14, p. 56A, 2001.
T. Nakamura, S. Muzuno, K. Matsumoto, Y. Sawa, H. Matsuda, and t. Nakamura, “Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF,” J Clin Invest, vol. 106, no. 12, pp. 1511-9, 2000.
R. Morishita, S. Nakamura, S. Hayashi, Y. Taniyama, A. Monguchi, T. Nagano, M. Taiji, H. Noguchi, S. Takeshita, K. Matsumoto, T. Nakamura, J. Higaki, and T. Ogihara, “Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy,” Hypertension, vol. 33, no. 6, pp. 1379-84, 1999.
W. Zeng, R. Ju, and M. Mao, “Therapeutic potential of hepatocyte growth factor against cerebral ischemia (Review),” Exp Ther Med, vol. 9, no. 2, pp. 283-8, 2015.
N. Tsuzuki, T. Miyazawa, K. Matsumoto, T. Nakamura, and K. Shima, “Hepatocyte growth factor reduces the infarct volume after transient focal cerebral ischemia in rats,” Neurol Res, vol. 23, no. 4, pp. 417-24, 2001.
M.J. Wayner, D.L. Armstrong, C.F. Phelix, J.W. Wright, and J.W. Harding, “Angiotensin IV enhances LTP in rat dentate gyrus in vivo,” Peptides, vol. 22, no. 9, pp. 1403-14, 2001.
T. Inoue. “Dynamics of calcium and its roles in the dendrite of the cerebellar Purkinje cell,” Keio J Med, vol. 52, no. 4, pp. 244-9, 2003.
E.M. Powell, S. Muhlfriedel, J. Bolz, and P. Levitt, “Differential regulation of thalamic and cortical axonal growth by hepatocyte growth factor/scatter factor,” Dev Neurosci, vol. 25, no. 2-4, pp. 197-206, 2003.
H. Gutierrez, X. Dolcet, M. Tolcos, and A. Davies, “HGF regulates the development of cortical pyramidal dendrites,” Development, vol. 131, no. 15, pp. 3717-26, 2004.
S. Faure, R. Chapo, D. Tallet, J. Javeliaud, J.M. Achard, and N. Oudart, “Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the rat mediated by AT(4) receptors,” J Physiol Pharmacol, vol. 57, no. 3, pp. 329-42, 2006.
P.R. Gard, “Cognitive-enhancing effects of angiotensin IV,” BMC Neurosci, vol. 9 (Suppl 2), pp. S2-S15, 2008.
O. von Bohlen und Halbach, “Angiotensin IV in the central nervous system,” Cell Tissue Res, vol. 311, no. 1, pp. 1-9, 2003.
J.W. Wright and J.W. Harding, “The brain angiotensin IV/AT4 receptor system as a new target for the treatment of Alzheimer’s disease,” Drug Dev Res, vol. 70, pp. 472-80, 2009.
J.W. Wright and J.W. Harding, “The angiotensin AT4 receptor subtype as a target for the treatment of memory dysfunction associated with Alzheimer’s disease,” J Renin Angiotensin Aldosterone Syst, vol. 9, no. 4, pp. 226-37, 2008.
M.F. Sardinia, J.M. Hanesworth, L.T. Krebs, and J.W. Harding, “AT4 receptor binding characteristics: D-amino acid- and glycine-substituted peptides,” Peptides, vol. 14, no. 5, pp. 949-54, 1993.
M.F. Sardinia, J.M. Hanesworth, F. Krishnan, and J.W. Harding, “AT4 receptor structure-binding relationship: N-terminal-modified angiotensin IV analogues,” Peptides, vol. 15, no. 8, pp. 1399-406, 1994.
E.A. Kramár, D.L. Armstrong, S. Ikeda, M.J. Wayner, J.W. Harding, and J.W. Wright, “The effects of angiotensin IV analogs on long-term potentiation within the CA1 region of the hippocampus in vitro,” Brain Res, vol. 897, no. 1-2, pp. 114-21, 2001.
L.T. Krebs, E.A. Kramar, J.M. Hanesworth, M.F. Sardinia, A.E. Ball, J.W. Wright and J.W. Harding, “Characterization of the binding properties and physiological action of divalinal-angiotensin IV, a putative AT4 receptor antagonist,” Regul Pept, vol. 67, no. 2, pp. 123-30, 1996.
T. Kobori, K. Goda, and K. Sugimoto, “Preparation of peptide derivatives as angiotensin IV receptor agonists,” WO, Article ID 97/03093 A1, 1997.
T. Kobori, K. Goda, and K. Sugimoto, “Preparation of amino acid derivatives as angiotensin IV receptor agonists,” WO, Article ID 98/05624 A1, 1998.
C.C. Benoist, L.H. Kawas, M. Zhu, K.A. Tyson, L. Stilmaker, S.M. Appleyard, J.W. Wright, G.A. Wayman, and J. W. Harding, “The precognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-Met system,” J Pharmacol Exp Ther, vol. 351, no. 2, pp. 390-402, 2014.
J.W. Wright, L. Stubley, E.S. Pederson, E.A. Kramar, J.J. Hanesworth, and J.W. Harding,, “Contributions of the brain angiotensin IV-AT4 receptor subtype system to spatial learning,” J Neurosci, vol. 19, no. 10, pp. 3952-61, 1999.
Z. Salehi and F. Rajaei, “Expression of hepatocyte growth factor in the serum and cerebrospinal fluid of patients with Parkinson’s disease,” J Clin Neurosci, vol. 17, no. 12, pp. 1553-6, 2010.
S. Kato, H. Funakoshi, T. Nakamura, M. Kato, I. Nakano, A. Hirano, and E. Ohama, “Expression of hepatocyte growth factor and c-Met in the anterior horn cells of the spinal cord in the patients with amyotrophic lateral sclerosis (ALS): Immunohistochemical studies on sporadic ALS and familial ALS with superoxide dismutase 1 gene mutation,” Acta Neurophathol, vol. 106, no. 2, pp. 112-20, 2003.
A. M. Muller, E. Jun, H.Conlon, and S.A. Sadiq, “Cerebrospinal hepatocyte growth factor levels correlate negatively with disease activity in multiple sclerosis,” J Neuroimmunol, vol. 251, no. 1-2, pp. 80-6, 2012.
M. Shimamura, N. Sato, M. Sata, K. Wakayama, T. Ogihara, and R. Monshita, “Expression of hepatocyte growth factor and c-Met after spinal cord injury in rats,” Brain Res, vol. 1151, no. 1-2, pp. 188-94, 2007.
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