TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration

Brain Research Bulletin

Volumn 121, Issue , 2016, Pages 192-200

  Ma, Li ^a   Zhang, Hui ^a   Liu, Na ^b   Wang, Pei qi ^a   Guo, Wen zhi ^a   Fu, Qiang ^a   Jiao, Lin bo ^a   Ma, Ya qun ^a   Mi, Wei Dong ^a  

^a CHINESE PLA GENERAL HOSPITAL   (China)

^b Affiliated Hospital of Chengde Mdical University   (China)

Author keywords

Cognition; LPS; Neuroinflammation; Neurosteroid; PK11195; TSPO

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; BETA SECRETASE 1; BRAIN DERIVED NEUROTROPHIC FACTOR; CYCLOOXYGENASE 2; INSULINASE; LIPOPOLYSACCHARIDE; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; NEUROPROTECTIVE AGENT; NEUROSTEROID; OUTER MEMBRANE PROTEIN; PROGESTERONE; TRANSLOCATOR PROTEIN 18 KDA; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID RECEPTOR; ANTIINFLAMMATORY AGENT; ASPARTIC PROTEINASE; BACE1 PROTEIN, MOUSE; BZRP PROTEIN, MOUSE; ELTANOLONE; ISOQUINOLINE DERIVATIVE; PTGS2 PROTEIN, MOUSE; SECRETASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BRAIN LEVEL; COGNITION; COGNITIVE DEFECT; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; HIPPOCAMPUS; LATENT PERIOD; LEARNING DISORDER; MALE; MICROGLIA; MORRIS WATER MAZE TEST; MOUSE; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEROIDOGENESIS; WESTERN BLOTTING; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; ENCEPHALITIS; GENE EXPRESSION REGULATION; GENETICS; MAZE TEST; METABOLISM; PATHOLOGY;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ANTI-INFLAMMATORY AGENTS; ASPARTIC ACID ENDOPEPTIDASES; BRAIN-DERIVED NEUROTROPHIC FACTOR; CYCLOOXYGENASE 2; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENCEPHALITIS; GENE EXPRESSION REGULATION; HIPPOCAMPUS; ISOQUINOLINES; LIPOPOLYSACCHARIDES; MALE; MAZE LEARNING; MICE; MICE, INBRED C57BL; PREGNANOLONE; PROGESTERONE; RECEPTORS, GABA;

EID: 84958166186     PISSN: 03619230     EISSN: 18732747     Source Type: Journal    
DOI: 10.1016/j.brainresbull.2016.02.001     Document Type: Article

References (77)

1. Agrawal V., Jaiswal M.K., Jaiswal Y.K. Lipopolysaccharide induces alterations in ovaries and serum level of progesterone and 17beta-estradiol in the mouse. Fertil. Steril. 2011, 95:1471-1474.
2. Barron A.M., Garcia-Segura L.M., Caruso D., Jayaraman A., Lee J.W., Melcangi R.C., Pike C.J. Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease. J. Neurosci. 2013, 33:8891-8897.
3. Bath K.G., Akins M.R., Lee F.S. BDNF control of adult SVZ neurogenesis. Dev. Psychobiol. 2012, 54:578-589.
4. Benraiss A., Chmielnicki E., Lerner K., Roh D., Goldman S.A. Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J. Neurosci. 2001, 21:6718-6731.
5. Billiards S.S., Walker D.W., Canny B.J., Hirst J.J. Endotoxin increases sleep and brain allopregnanolone concentrations in newborn lambs. Pediatr. Res. 2002, 52:892-899.
6. Billiards S.S., Nguyen P.N., Scheerlinck J.P., Phillips D.J., Canny B.J., Walker D.W., Hirst J.J. Hypoxia potentiates endotoxin-induced allopregnanolone concentrations in the newborn brain. Biol. Neonate 2006, 90:258-267.
7. Caccamo A., Oddo S., Sugarman M.C., Akbari Y., LaFerla F.M. Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol. Aging 2005, 26:645-654.
8. Cagnin A., Rossor M., Sampson E.L., Mackinnon T., Banati R.B. In vivo detection of microglial activation in frontotemporal dementia. Ann. Neurol. 2004, 56:894-897.
9. Chen S., Wang J.M., Irwin R.W., Yao J., Liu L., Brinton R.D. Allopregnanolone promotes regeneration and reduces beta-amyloid burden in a preclinical model of Alzheimer's disease. PLoS One 2011, 6:e24293.
10. Choi J., Ifuku M., Noda M., Guilarte T.R. Translocator protein (18 kDa)/peripheral benzodiazepine receptor specific ligands induce microglia functions consistent with an activated state. Glia 2011, 59:219-230.
11. Cook D.G., Leverenz J.B., McMillan P.J., Kulstad J.J., Ericksen S., Roth R.A., Schellenberg G.D., Jin L.W., Kovacina K.S., Craft S. Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele. Am. J. Pathol. 2003, 162:313-319.
12. Costa B., Da Pozzo E., Chelli B., Simola N., Morelli M., Luisi M., Maccheroni M., Taliani S., Simorini F., Da Settimo F., Martini C. Anxiolytic properties of a 2-phenylindolglyoxylamide TSPO ligand: stimulation of in vitro neurosteroid production affecting GABAA receptor activity. Psychoneuroendocrinology 2011, 36:463-472.
13. Daugherty D.J., Selvaraj V., Chechneva O.V., Liu X.B., Pleasure D.E., Deng W. A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol. Med. 2013, 5:891-903.
14. DiCarlo G., Wilcock D., Henderson D., Gordon M., Morgan D. Intrahippocampal LPS injections reduce Abeta load in APP + PS1 transgenic mice. Neurobiol. Aging 2001, 22:1007-1012.
15. Dorfman V.B., Pasquini L., Riudavets M., Lopez-Costa J.J., Villegas A., Troncoso J.C., Lopera F., Castano E.M., Morelli L. Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease. Neurobiol. Aging 2010, 31:1743-1757.
16. Edison P., Archer H.A., Gerhard A., Hinz R., Pavese N., Turkheimer F.E., Hammers A., Tai Y.F., Fox N., Kennedy A., Rossor M., Brooks D.J. Microglia, amyloid, and cognition in Alzheimer's disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol. Dis. 2008, 32:412-419.
17. Espinosa-Oliva A.M., de Pablos R.M., Villaran R.F., Arguelles S., Venero J.L., Machado A., Cano J. Stress is critical for LPS-induced activation of microglia and damage in the rat hippocampus. Neurobiol. Aging 2011, 32:85-102.
18. Farges R.C., Torres S.R., Ferrara P., Ribeiro-do-Valle R.M. Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine receptor ligands. Life Sci. 2004, 74:1387-1395.
19. Garcia-Ovejero D., Azcoitia I., Doncarlos L.L., Melcangi R.C., Garcia-Segura L.M. Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones. Brain Res. Brain Res. Rev. 2005, 48:273-286.
20. Gerhard A., Pavese N., Hotton G., Turkheimer F., Es M., Hammers A., Eggert K., Oertel W., Banati R.B., Brooks D.J. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol. Dis. 2006, 21:404-412.
21. Ghezzi P., Santo E.D., Sacco S., Foddi C., Barbaccia M.L., Mennini T. Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS-induced TNF production. Eur. Cytokine Netw. 2000, 11:464-469.
22. Goddard L.M., Ton A.N., Org T., Mikkola H.K., Iruela-Arispe M.L. Selective suppression of endothelial cytokine production by progesterone receptor. Vascul. Pharmacol. 2013, 59:36-43.
23. Gong Q.H., Wang Q., Pan L.L., Liu X.H., Huang H., Zhu Y.Z. Hydrogen sulfide attenuates lipopolysaccharide-induced cognitive impairment: a pro-inflammatory pathway in rats. Pharmacol. Biochem. Behav. 2010, 96:52-58.
24. Guan Z., Fang J. Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav. Immun. 2006, 20:64-71.
25. Guennoun R., Labombarda F., Gonzalez Deniselle M.C., Liere P., De Nicola A.F., Schumacher M. Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection. J. Steroid Biochem. Mol. Biol. 2015, 146:48-61.
26. Haber M., Abdel Baki S.G., Grin'kina N.M., Irizarry R., Ershova A., Orsi S., Grill R.J., Dash P., Bergold P.J. Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury. Exp. Neurol. 2013, 249:169-177.
27. Harberts E., Datta D., Chen S., Wohler J.E., Oh U., Jacobson S. Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients. J. Neuroimmune Pharmacol. 2013, 8:51-57.
28. Herber D.L., Mercer M., Roth L.M., Symmonds K., Maloney J., Wilson N., Freeman M.J., Morgan D., Gordon M.N. Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J. Neuroimmune Pharmacol. 2007, 2:222-231.
29. Hussain R., El-Etr M., Gaci O., Rakotomamonjy J., Macklin W.B., Kumar N., Sitruk-Ware R., Schumacher M., Ghoumari A.M. Progesterone and Nestorone facilitate axon remyelination: a role for progesterone receptors. Endocrinology 2011, 152:3820-3831.
30. Irwin R.W., Wang J.M., Chen S., Brinton R.D. Neuroregenerative mechanisms of allopregnanolone in Alzheimer's disease. Front. Endocrinol. (Lausanne) 2011, 2:117.
31. Jaeger L.B., Dohgu S., Sultana R., Lynch J.L., Owen J.B., Erickson M.A., Shah G.N., Price T.O., Fleegal-Demotta M.A., Butterfield D.A., Banks W.A. Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer's disease. Brain Behav. Immun. 2009, 23:507-517.
32. Kahn M.S., Kranjac D., Alonzo C.A., Haase J.H., Cedillos R.O., McLinden K.A., Boehm G.W., Chumley M.J. Prolonged elevation in hippocampal Abeta and cognitive deficits following repeated endotoxin exposure in the mouse. Behav. Brain Res. 2012, 229:176-184.
33. Karlstetter M., Nothdurfter C., Aslanidis A., Moeller K., Horn F., Scholz R., Neumann H., Weber B.H., Rupprecht R., Langmann T. Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. J. Neuroinflammation 2014, 11:3.
34. Kranjac D., McLinden K.A., Deodati L.E., Papini M.R., Chumley M.J., Boehm G.W. Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice. Brain Behav. Immun. 2012, 26:109-121.
35. Labombarda F., Pianos A., Liere P., Eychenne B., Gonzalez S., Cambourg A., De Nicola A.F., Schumacher M., Guennoun R. Injury elicited increase in spinal cord neurosteroid content analyzed by gas chromatography mass spectrometry. Endocrinology 2006, 147:1847-1859.
36. Leal G., Afonso P.M., Salazar I.L., Duarte C.B. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res. 2015, 1621:82-101.
37. Leaver K.R., Reynolds A., Bodard S., Guilloteau D., Chalon S., Kassiou M. Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum. ACS Chem. Neurosci. 2012, 3:114-119.
38. Lee J.W., Lee Y.K., Yuk D.Y., Choi D.Y., Ban S.B., Oh K.W., Hong J.T. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J. Neuroinflammation 2008, 5:37.
39. Lei B., Mace B., Dawson H.N., Warner D.S., Laskowitz D.T., James M.L. Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-microglia. PLoS One 2014, 9:e103969.
40. Liu A., Margaill I., Zhang S., Labombarda F., Coqueran B., Delespierre B., Liere P., Marchand-Leroux C., O'Malley B.W., Lydon J.P., De Nicola A.F., Sitruk-Ware R., Mattern C., Plotkine M., Schumacher M., Guennoun R. Progesterone receptors: a key for neuroprotection in experimental stroke. Endocrinology 2012, 153:3747-3757.
41. Martinez Calejman C., Astort F., Di Gruccio J.M., Repetto E.M., Mercau M., Giordanino E., Sanchez R., Pignataro O., Arias P., Cymeryng C.B. Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-activation. Mol. Cell Endocrinol. 2011, 337:1-6.
42. Meffre D., Pianos A., Liere P., Eychenne B., Cambourg A., Schumacher M., Stein D.G., Guennoun R. Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: analysis by gas chromatography/mass spectrometry. Endocrinology 2007, 148:2505-2517.
43. Miguel-Alvarez M., Santos-Lozano A., Sanchis-Gomar F., Fiuza-Luces C., Pareja-Galeano H., Garatachea N., Lucia A. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect. Drugs Aging 2015, 32:139-147.
44. Milenkovic V.M., Rupprecht R., Wetzel C.H. The translocator protein 18 kDa (TSPO) and its role in mitochondrial biology and psychiatric disorders. Mini. Rev. Med. Chem. 2015, 15:366-372.
45. Mills C., Makwana M., Wallace A., Benn S., Schmidt H., Tegeder I., Costigan M., Brown R.H., Raivich G., Woolf C.J. Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Eur. J. Neurosci. 2008, 27:937-946.
46. Mitro N., Cermenati G., Giatti S., Abbiati F., Pesaresi M., Calabrese D., Garcia-Segura L.M., Caruso D., Melcangi R.C. LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals. Neurochem. Int. 2012, 60:616-621.
47. Nakajima K., Tohyama Y., Kohsaka S., Kurihara T. Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. J. Neurochem. 2002, 80:697-705.
48. Ouchi Y., Yoshikawa E., Sekine Y., Futatsubashi M., Kanno T., Ogusu T., Torizuka T. Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann. Neurol. 2005, 57:168-175.
49. Papadopoulos V., Baraldi M., Guilarte T.R., Knudsen T.B., Lacapere J.J., Lindemann P., Norenberg M.D., Nutt D., Weizman A., Zhang M.R., Gavish M. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol. Sci. 2006, 27:402-409.
50. Pavese N., Gerhard A., Tai Y.F., Ho A.K., Turkheimer F., Barker R.A., Brooks D.J., Piccini P. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 2006, 66:1638-1643.
51. Perez A., Morelli L., Cresto J.C., Castano E.M. Degradation of soluble amyloid beta-peptides 1-40, 1-42, and the Dutch variant 1-40Q by insulin degrading enzyme from Alzheimer disease and control brains. Neurochem. Res. 2000, 25:247-255.
52. Price J.C., Bromfield J.J., Sheldon I.M. Pathogen-associated molecular patterns initiate inflammation and perturb the endocrine function of bovine granulosa cells from ovarian dominant follicles via TLR2 and TLR4 pathways. Endocrinology 2013, 154:3377-3386.
53. Quinn J., Montine T., Morrow J., Woodward W.R., Kulhanek D., Eckenstein F. Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease. J. Neuroimmunol. 2003, 137:32-41.
54. Reddy D.S. Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog. Brain Res. 2010, 186:113-137.
55. Rissanen E., Tuisku J., Rokka J., Paavilainen T., Parkkola R., Rinne J.O., Airas L. In vivo detection of diffuse inflammation in secondary progressive multiple sclerosis using PET imaging and the radioligand 11C-PK11195. J. Nucl. Med. 2014, 55:939-944.
56. Robertson C.L., Fidan E., Stanley R.M., Noje C., Bayir H. Progesterone for neuroprotection in pediatric traumatic brain injury. Pediatr. Crit. Care Med. 2015, 16:236-244.
57. Rupprecht R., Papadopoulos V., Rammes G., Baghai T.C., Fan J., Akula N., Groyer G., Adams D., Schumacher M. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 2010, 9:971-988.
58. Ryu J.K., Choi H.B., McLarnon J.G. Peripheral benzodiazepine receptor ligand PK11195 reduces microglial activation and neuronal death in quinolinic acid-injected rat striatum. Neurobiol. Dis. 2005, 20:550-561.
59. Schnydrig S., Korner L., Landweer S., Ernst B., Walker G., Otten U., Kunz D. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. Neurosci. Lett. 2007, 429:69-73.
60. Stargardt A., Gillis J., Kamphuis W., Wiemhoefer A., Kooijman L., Raspe M., Benckhuijsen W., Drijfhout J.W., Hol E.M., Reits E. Reduced amyloid-beta degradation in early Alzheimer's disease but not in the APPswePS1dE9 and 3xTg-AD mouse models. Aging Cell 2013, 12:499-507.
61. Steinman L. Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:20595-20596.
62. Totis M., Kremers P., Batt A.M., Van Cantfort J., Siest G., Gielen J. Induction of liver microsomal cytochrome P-450 isozymes by 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide. Xenobiotica 1989, 19:857-866.
63. Tu L.N., Zhao A.H., Stocco D.M., Selvaraj V. PK11195 effect on steroidogenesis is not mediated through the translocator protein (TSPO). Endocrinology 2015, 156:1033-1039.
64. Veiga S., Carrero P., Pernia O., Azcoitia I., Garcia-Segura L.M. Translocator protein 18 kDa is involved in the regulation of reactive gliosis. Glia 2007, 55:1426-1436.
65. Vepsalainen S., Hiltunen M., Helisalmi S., Wang J., van Groen T., Tanila H., Soininen H. Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology. Neurosci. Lett. 2008, 438:216-220.
66. Versijpt J., Debruyne J.C., Van Laere K.J., De Vos F., Keppens J., Strijckmans K., Achten E., Slegers G., Dierckx R.A., Korf J., De Reuck J.L. Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult. Scler. 2005, 11:127-134.
67. Vowinckel E., Reutens D., Becher B., Verge G., Evans A., Owens T., Antel J.P. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Neurosci. Res. 1997, 50:345-353.
68. 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. 2005, 25:4706-4718.
69. Wang R., Wang S., Malter J.S., Wang D.S. Effects of 4-hydroxy-nonenal and Amyloid-beta on expression and activity of endothelin converting enzyme and insulin degrading enzyme in SH-SY5Y cells. J. Alzheimers Dis. 2009, 17:489-501.
70. Wang J.M., Singh C., Liu L., Irwin R.W., Chen S., Chung E.J., Thompson R.F., Brinton R.D. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:6498-6503.
71. Wu C.W., Chen Y.C., Yu L., Chen H.I., Jen C.J., Huang A.M., Tsai H.J., Chang Y.T., Kuo Y.M. Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. J. Neurochem. 2007, 103:2471-2481.
72. Yasuno F., Ota M., Kosaka J., Ito H., Higuchi M., Doronbekov T.K., Nozaki S., Fujimura Y., Koeda M., Asada T., Suhara T. Increased binding of peripheral benzodiazepine receptor in Alzheimer's disease measured by positron emission tomography with [11C]DAA1106. Biol. Psychiatry 2008, 64:835-841.
73. Yousuf S., Atif F., Sayeed I., Tang H., Stein D.G. Progesterone in transient ischemic stroke: a dose-response study. Psychopharmacology (Berl) 2014, 231:3313-3323.
74. Zhang L.M., Qiu Z.K., Zhao N., Chen H.X., Liu Y.Q., Xu J.P., Zhang Y.Z., Yang R.F., Li Y.F. Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder. Int. J. Neuropsychopharmacol. 2014, 17:1659-1669.
75. Zhao Z., Xiang Z., Haroutunian V., Buxbaum J.D., Stetka B., Pasinetti G.M. Insulin degrading enzyme activity selectively decreases in the hippocampal formation of cases at high risk to develop Alzheimer's disease. Neurobiol. Aging 2007, 28:824-830.
76. do Rego J.L., Vaudry D., Vaudry H. The non-benzodiazepine anxiolytic drug etifoxine causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis. PLoS One 2015, 10:e0120473.
77. Zurcher N.R., Loggia M.L., Lawson R., Chonde D.B., Izquierdo-Garcia D., Yasek J.E., Akeju O., Catana C., Rosen B.R., Cudkowicz M.E., Hooker J.M., Atassi N. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin. 2015, 7:409-414.