PACAP27 prevents Parkinson-like neuronal loss and motor deficits but not microglia activation induced by prostaglandin J2

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1842, Issue 9, 2014, Pages 1707-1719

  Shivers, Kai Yvonne ^a   Nikolopoulou, Anastasia ^b   Machlovi, Saima Ishaq ^a   Vallabhajosula, Shankar ^b   Figueiredo Pereira, Maria E ^a  

^a CITY UNIVERSITY OF NEW YORK   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Microglia; PACAP; Parkinson; PET; PK11195; Prostaglandin J2

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR; CYCLOOXYGENASE 2; H 1172; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; PROSTAGLANDIN J2; UBIQUITINATED PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BEHAVIOR CHANGE; BRAIN CELL CULTURE; BRAIN CORTEX; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CORPUS STRIATUM; DOPAMINERGIC NERVE CELL; DOPAMINERGIC SYSTEM; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; IN VITRO STUDY; MALE; MICROGLIA; MOTOR PERFORMANCE; MOUSE; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; PARKINSONISM; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PSYCHOMOTOR DISORDER; SIGNAL TRANSDUCTION; STEREOLOGY; SUBSTANTIA NIGRA; SUBSTANTIA NIGRA PARS COMPACTA; VENTRAL TEGMENTUM;

MICROGLIA; PACAP; PARKINSON; PET; PK11195; PROSTAGLANDIN J2;

ANIMALS; ANTINEOPLASTIC AGENTS; BEHAVIOR, ANIMAL; DISEASE MODELS, ANIMAL; ENCEPHALITIS; IMMUNOENZYME TECHNIQUES; MALE; MICE; MICROGLIA; MOTOR SKILLS DISORDERS; NEURONS; PARKINSON DISEASE; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; POSITRON-EMISSION TOMOGRAPHY; PROSTAGLANDIN D2;

EID: 84904089007     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2014.06.020     Document Type: Article

References (92)

1. Abdel-Halim M.S., Hamberg M., Sjoquist B., Anggard E. Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain. Prostaglandins 1977, 14:633-643.
2. Anglade P., Mouatt-Prigent A., Agid Y., Hirsch E. Synaptic plasticity in the caudate nucleus of patients with Parkinson's disease. Neurodegeneration 1996, 5:121-128.
3. Aoki T., Narumiya S. Prostaglandins and chronic inflammation. Trends Pharmacol. Sci. 2012, 33:304-311.
4. Atlasz T., Szabadfi K., Kiss P., Tamas A., Toth G., Reglodi D., Gabriel R. Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration. Brain Res. Bull. 2010, 81:497-504.
5. Banati R.B. Visualising microglial activation in vivo. Glia 2002, 40:206-217.
6. Baquet Z.C., Williams D., Brody J., Smeyne R.J. A comparison of model-based (2D) and design-based (3D) stereological methods for estimating cell number in the substantia nigra pars compacta (SNpc) of the C57BL/6J mouse. Neuroscience 2009, 161:1082-1090.
7. Bartels A.L., Leenders K.L. Cyclooxygenase and neuroinflammation in Parkinson's disease neurodegeneration. Curr. Neuropharmacol. 2010, 8:62-68.
8. Becker C., Jick S.S., Meier C.R. Risk of stroke in patients with idiopathic Parkinson disease. Parkinsonism Relat. Disord. 2010, 16:31-35.
9. Bernheimer H., Birkmayer W., Hornykiewicz O., Jellinger K., Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. Neurol. Sci. 1973, 20:415-455.
10. Betarbet R., Poisik O., Sherer T.B., Greenamyre J.T. Differential expression and ser897 phosphorylation of striatal N-methyl-d-aspartate receptor subunit NR1 in animal models of Parkinson's disease. Exp. Neurol. 2004, 187:76-85.
11. Calabresi P., Picconi B., Tozzi A., Di F.M. Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci. 2007, 30:211-219.
12. Carvalho M.M., Campos F.L., Coimbra B., Pego J.M., Rodrigues C., Lima R., Rodrigues A.J., Sousa N., Salgado A.J. Behavioral characterization of the 6-hydroxidopamine model of Parkinson's disease and pharmacological rescuing of non-motor deficits. Mol. Neurodegener. 2013, 8:14.
13. Ching A.S., Kuhnast B., Damont A., Roeda D., Tavitian B., Dolle F. Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases. Insights Imaging 2012, 3:111-119.
14. Chiu E.K., Richardson J.S. Behavioral and neurochemical aspects of prostaglandins in brain function. Gen. Pharmacol. 1985, 16:163-175.
15. Cox H.M. Pituitary adenylate cyclase activating polypeptides, PACAP-27 and PACAP-38: stimulators of electrogenic ion secretion in the rat small intestine. Br. J. Pharmacol. 1992, 106:498-502.
16. Day M., Wang Z., Ding J., An X., Ingham C.A., Shering A.F., Wokosin D., Ilijic E., Sun Z., Sampson A.R., Mugnaini E., Deutch A.Y., Sesack S.R., Arbuthnott G.W., Surmeier D.J. Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. Nat. Neurosci. 2006, 9:251-259.
17. Deguil J., Chavant F., Lafay-Chebassier C., Perault-Pochat M.C., Fauconneau B., Pain S. Neuroprotective effect of PACAP on translational control alteration and cognitive decline in MPTP parkinsonian mice. Neurotox. Res. 2010, 17:142-155.
18. Dejda A., Seaborn T., Bourgault S., Touzani O., Fournier A., Vaudry H., Vaudry D. PACAP and a novel stable analog protect rat brain from ischemia: Insight into the mechanisms of action. Peptides 2011, 32:1207-1216.
19. Deleidi M., Gasser T. The role of inflammation in sporadic and familial Parkinson's disease. Cell. Mol. Life Sci. 2013 Nov, 70(20):4259-4273.
20. Dogrukol-Ak D., Tore F., Tuncel N. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. Curr. Pharm. Des. 2004, 10:1325-1340.
21. Ebrahimi-Fakhari D., Wahlster L., McLean P.J. Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol. 2012, 124:153-172.
22. Esposito E., Di M.V., Benigno A., Pierucci M., Crescimanno G., Di G.G. Non-steroidal anti-inflammatory drugs in Parkinson's disease. Exp. Neurol. 2007 Jun, 205:295-312. Epub 2007 Feb 23.
23. Fahn S., Libsch L.R., Cutler R.W. Monoamines in the human neostriatum: topographic distribution in normals and in Parkinson's disease and their role in akinesia, rigidity, chorea, and tremor. J. Neurol. Sci. 1971, 14:427-455.
24. Fearnley J.M., Lees A.J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 1991, 114(Pt 5):2283-2301.
25. Feng Z., Li D., Fung P.C., Pei Z., Ramsden D.B., Ho S.L. COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice. Neuroreport 2003, 14:1927-1929.
26. Golovko M.Y., Murphy E.J. Brain prostaglandin formation is increased by alpha-synuclein gene-ablation during global ischemia. Neurosci. Lett. 2008, 432:243-247.
27. Grealish S., Mattsson B., Draxler P., Bjorklund A. Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease. Eur. J. Neurosci. 2010, 31:2266-2278.
28. Hata A.N., Zent R., Breyer M.D., Breyer R.M. Expression and molecular pharmacology of the mouse CRTH2 receptor. J. Pharmacol. Exp. Ther. 2003, 306:463-470.
29. Henderson J.M., Annett L.E., Ryan L.J., Chiang W., Hidaka S., Torres E.M., Dunnett S.B. Subthalamic nucleus lesions induce deficits as well as benefits in the hemiparkinsonian rat. Eur. J. Neurosci. 1999, 11:2749-2757.
30. Herlong J.L., Scott T.R. Positioning prostanoids of the D and J series in the immunopathogenic scheme. Immunol. Lett. 2006, 102:121-131.
31. Hickey R.W., Adelson P.D., Johnnides M.J., Davis D.S., Yu Z., Rose M.E., Chang Y.F., Graham S.H. Cyclooxygenase-2 activity following traumatic brain injury in the developing rat. Pediatr. Res. 2007, 62:271-276.
32. Higdon A.N., Landar A., Barnes S., Darley-Usmar V.M. The electrophile responsive proteome: integrating proteomics and lipidomics with cellular function. Antioxid. Redox Signal. 2012, 17:1580-1589.
33. Hirsch E., Graybiel A.M., Agid Y.A. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 1988, 334:345-348.
34. Huang H., Wang H., Figueiredo-Pereira M.E. Regulating the ubiquitin/proteasome pathway via cAMP-signaling: neuroprotective potential. Cell Biochem. Biophys. 2013, 67:55-66.
35. Hutson C.B., Lazo C.R., Mortazavi F., Giza C.C., Hovda D., Chesselet M.F. Traumatic brain injury in adult rats causes progressive nigrostriatal dopaminergic cell loss and enhanced vulnerability to the pesticide paraquat. J. Neurotrauma 2011, 28:1783-1801.
36. Iadecola C., Gorelick P.B. The Janus face of cyclooxygenase-2 in ischemic stroke: shifting toward downstream targets. Stroke 2005, 36:182-185.
37. Ishii T., Sakurai T., Usami H., Uchida K. Oxidative modification of proteasome: identification of an oxidation-sensitive subunit in 26s proteasome. Biochemistry 2005, 44:13893-13901.
38. Joo K.M., Chung Y.H., Kim M.K., Nam R.H., Lee B.L., Lee K.H., Cha C.I. Distribution of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC1, VPAC2, and PAC1 receptor) in the rat brain. J. Comp. Neurol. 2004, 476:388-413.
39. Kierdorf K., Prinz M. Factors regulating microglia activation. Front. Cell. Neurosci. 2013, 7:44.
40. Klivenyi P., Gardian G., Calingasan N.Y., Yang L., Beal M.F. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J. Mol. Neurosci. 2003, 21:191-198.
41. Koharudin L.M., Liu H., Di M.R., Kodali R.B., Graham S.H., Gronenborn A.M. Cyclopentenone prostaglandin-induced unfolding and aggregation of the Parkinson disease-associated UCH-L1. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:6835-6840.
42. Kondo M., Oya-Ito T., Kumagai T., Osawa T., Uchida K. Cyclopentenone prostaglandins as potential inducers of intracellular oxidative stress. J. Biol. Chem. 2001, 276:12076-12083.
43. Kondo M., Shibata T., Kumagai T., Osawa T., Shibata N., Kobayashi M., Sasaki S., Iwata M., Noguchi N., Uchida K. 15-Deoxy-delta(12,14)-prostaglandin J(2): the endogenous electrophile that induces neuronal apoptosis. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:7367-7372.
44. Koprich J.B., Reske-Nielsen C., Mithal P., Isacson O. Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. J. Neuroinflammation 2008, 5:8.
45. Kunz T., Marklund N., Hillered L., Oliw E.H. Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat. J. Neurotrauma 2002, 19:1051-1064.
46. Li Z., Jansen M., Ogburn K., Salvatierra L., Hunter L., Mathew S., Figueiredo-Pereira M.E. Neurotoxic prostaglandin J2 enhances cyclooxygenase-2 expression in neuronal cells through the p38MAPK pathway: a death wish?. J. Neurosci. Res. 2004, 78:824-836.
47. Li Z., Melandri F., Berdo I., Jansen M., Hunter L., Wright S., Valbrun D., Figueiredo-Pereira M.E. Delta12-Prostaglandin J2 inhibits the ubiquitin hydrolase UCH-L1 and elicits ubiquitin-protein aggregation without proteasome inhibition. Biochem. Biophys. Res. Commun. 2004, 319:1171-1180.
48. Liang X., Wu L., Hand T., Andreasson K. Prostaglandin D2 mediates neuronal protection via the DP1 receptor. J. Neurochem. 2005, 92:477-486.
49. Liang X., Wu L., Wang Q., Hand T., Bilak M., McCullough L., Andreasson K. Function of COX-2 and prostaglandins in neurological disease. J. Mol. Neurosci. 2007, 33:94-99.
50. Liu H., Li W., Ahmad M., Miller T.M., Rose M.E., Poloyac S.M., Uechi G., Balasubramani M., Hickey R.W., Graham S.H. Modification of ubiquitin-C-terminal hydrolase-L1 by cyclopentenone prostaglandins exacerbates hypoxic injury. Neurobiol. Dis. 2011, 41:318-328.
51. Liu H., Li W., Ahmad M., Rose M.E., Miller T.M., Yu M., Chen J., Pascoe J.L., Poloyac S.M., Hickey R.W., Graham S.H. Increased generation of cyclopentenone prostaglandins after brain ischemia and their role in aggregation of ubiquitinated proteins in neurons. Neurotox. Res. 2013, 24:191-204.
52. Liu H., Li W., Rose M.E., Pascoe J.L., Miller T.M., Ahmad M., Poloyac S.M., Hickey R.W., Graham S.H. Prostaglandin D toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites. Neurotoxicology 2013, 39C:35-44.
53. Mao S.S., Hua R., Zhao X.P., Qin X., Sun Z.Q., Zhang Y., Wu Y.Q., Jia M.X., Cao J.L., Zhang Y.M. Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-kappaB pathway. J. Neurotrauma 2012, 29:1941-1959.
54. Martinez B., Perez-Castillo A., Santos A. The mitochondrial respiratory complex I is a target for 15-deoxy-delta12,14-prostaglandin J2 action. J. Lipid Res. 2005, 46:736-743.
55. McGeer E.G., McGeer P.L. The role of anti-inflammatory agents in Parkinson's disease. CNS Drugs 2007, 21:789-797.
56. Meredith G.E., Kang U.J. Behavioral models of Parkinson's disease in rodents: a new look at an old problem. Mov. Disord. 2006, 21:1595-1606.
57. Metcalfe M.J., Huang Q., Figueiredo-Pereira M.E. Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP. Cell Death Dis. 2012, 3:e326.
58. Mogi M., Harada M., Kondo T., Riederer P., Inagaki H., Minami M., Nagatsu T. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci. Lett. 1994, 180:147-150.
59. Monneret G., Li H., Vasilescu J., Rokach J., Powell W.S. 15-Deoxy-delta 12,14-prostaglandins D2 and J2 are potent activators of human eosinophils. J. Immunol. 2002, 168:3563-3569.
60. Moody T.W., Ito T., Osefo N., Jensen R.T. VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studies. Curr. Opin. Endocrinol. Diabetes Obes. 2011, 18:61-67.
61. Mullally J.E., Moos P.J., Edes K., Fitzpatrick F.A. Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway. J. Biol. Chem. 2001, 276:30366-30373.
62. Myeku N., Wang H., Figueiredo-Pereira M.E. cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons. Neurosci. Lett. 2012, 527:126-131.
63. Nelson E.L., Liang C.L., Sinton C.M., German D.C. Midbrain dopaminergic neurons in the mouse: computer-assisted mapping. J. Comp. Neurol. 1996, 369:361-371.
64. Ogburn K.D., Bottiglieri T., Wang Z., Figueiredo-Pereira M.E. Prostaglandin J2 reduces catechol-O-methyltransferase activity and enhances dopamine toxicity in neuronal cells. Neurobiol. Dis. 2006, 22:294-301.
65. Ogburn K.D., Figueiredo-Pereira M.E. Cytoskeleton/endoplasmic reticulum collapse induced by prostaglandin J2 parallels centrosomal deposition of ubiquitinated protein aggregates. J. Biol. Chem. 2006, 281:23274-23284.
66. Ohtaki H., Satoh A., Nakamachi T., Yofu S., Dohi K., Mori H., Ohara K., Miyamoto K., Hashimoto H., Shintani N., Baba A., Matsunaga M., Shioda S. Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor. J. Mol. Neurosci. 2010, 42:397-403.
67. Paxinos G., Franklin K.B.J. The Mouse Brain in Stereotaxic Coordinates 2001, Academic, San Diego.
68. Picconi B., Gardoni F., Centonze D., Mauceri D., Cenci M.A., Bernardi G., Calabresi P., Di L.M. Abnormal Ca2+-calmodulin-dependent protein kinase II function mediates synaptic and motor deficits in experimental parkinsonism. J. Neurosci. 2004, 24:5283-5291.
69. Pierre S.R., Lemmens M.A., Figueiredo-Pereira M.E. Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice. J. Neuroinflammation 2009, 6:18.
70. Pott Godoy M.C., Tarelli R., Ferrari C.C., Sarchi M.I., Pitossi F.J. Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease. Brain 2008, 131:1880-1894.
71. Reglodi D., Kiss P., Lubics A., Tamas A. Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr. Pharm. Des. 2011, 17:962-972.
72. Reglodi D., Lubics A., Tamas A., Szalontay L., Lengvari I. Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson's disease. Behav. Brain Res. 2004, 151:303-312.
73. Rodriguez-Grande B., Blackabey V., Gittens B., Pinteaux E., Denes A. Loss of substance P and inflammation precede delayed neurodegeneration in the substantia nigra after cerebral ischemia. Brain Behav. Immun. 2013, 29:51-61.
74. Satoh T., Lipton S.A. Redox regulation of neuronal survival mediated by electrophilic compounds. Trends Neurosci. 2007, 30:37-45.
75. Schallert T., Fleming S.M., Leasure J.L., Tillerson J.L., Bland S.T. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 2000, 39:777-787.
76. Shibata T., Yamada T., Kondo M., Tanahashi N., Tanaka K., Nakamura H., Masutani H., Yodoi J., Uchida K. An endogenous electrophile that modulates the regulatory mechanism of protein turnover: inhibitory effects of 15-deoxy-delta(12,14)-prostaglandin J2 on proteasome. Biochemistry 2003, 42:13960-13968.
77. Shih A.Y., Fernandes H.B., Choi F.Y., Kozoriz M.G., Liu Y., Li P., Cowan C.M., Klegeris A. Policing the police: astrocytes modulate microglial activation. J. Neurosci. 2006, 26:3887-3888.
78. Silveira M.S., Linden R. Neuroprotection by cAMP: another brick in the wall. Adv. Exp. Med. Biol. 2006, 557:164-176.
79. Sousa N., Almeida O.F., Wotjak C.T. A hitchhiker's guide to behavioral analysis in laboratory rodents. Genes Brain Behav. 2006, 5(Suppl. 2):5-24.
80. Straus D.S., Glass C.K. Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med. Res. Rev. 2001, 21:185-210.
81. Takei N., Skoglosa Y., Lindholm D. Neurotrophic and neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on mesencephalic dopaminergic neurons. J. Neurosci. Res. 1998, 54:698-706.
82. Tan Y.V., Waschek J.A. Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis. ASN Neuro 2011, 3. (p.pii:e00065).
83. Tanaka S., Ishii A., Ohtaki H., Shioda S., Yoshida T., Numazawa S. Activation of microglia induces symptoms of Parkinson's disease in wild-type, but not in IL-1 knockout mice. J. Neuroinflammation 2013, 10:143.
84. Tansey M.G., Goldberg M.S. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol. Dis. 2010, 37:510-518.
85. Teismann P., Tieu K., Choi D.K., Wu D.C., Naini A., Hunot S., Vila M., Jackson-Lewis V., Przedborski S. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:5473-5478.
86. Uchida H., Yokoyama H., Kimoto H., Kato H., Araki T. Long-term changes in the ipsilateral substantia nigra after transient focal cerebral ischaemia in rats. Int. J. Exp. Pathol. 2010, 91:256-266.
87. Uchida K., Shibata T. 15-Deoxy-delta(12,14)-prostaglandin J2: an electrophilic trigger of cellular responses. Chem. Res. Toxicol. 2008, 21:138-144.
88. Venneti S., Lopresti B.J., Wiley C.A. Molecular imaging of microglia/macrophages in the brain. Glia 2013, 61:10-23.
89. Wang G., Pan J., Tan Y.Y., Sun X.K., Zhang Y.F., Zhou H.Y., Ren R.J., Wang X.J., Chen S.D. Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum. Neuropeptides 2008, 42:267-276.
90. Wang Z., Aris V.M., Ogburn K.D., Soteropoulos P., Figueiredo-Pereira M.E. Prostaglandin J2 alters pro-survival and pro-death gene expression patterns and 26S proteasome assembly in human neuroblastoma cells. J. Biol. Chem. 2006, 281:21377-21386.
91. Warraich S.T., Allbutt H.N., Billing R., Radford J., Coster M.J., Kassiou M., Henderson J.M. Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model. Brain Res. Bull. 2009, 78:85-90.
92. Watson M.B., Nobuta H., Abad C., Lee S.K., Bala N., Zhu C., Richter F., Chesselet M.F., Waschek J.A. PACAP deficiency sensitizes nigrostriatal dopaminergic neurons to paraquat-induced damage and modulates central and peripheral inflammatory activation in mice. Neuroscience 2013, 240:277-286.