Abstract
We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson’s disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (containing the substantia nigra pars compacta; SNc) and striatum were processed for glial fibrillary acidic protein (to label astrocytes; GFAP) and ionised calcium-binding adaptor molecule 1 (to label microglia; IBA1) immunohistochemistry. Cell counts were undertaken using stereology, and cell body sizes were measured using ImageJ. Our results showed that NIr treatment reduced dramatically (~75 %) MPTP-induced astrogliosis in both the SNc and striatum. Among microglia, however, NIr had a more limited impact in both nuclei; although there was a reduction in overall cell size, there were no changes in the number of microglia in the MPTP-treated monkeys after NIr treatment. In summary, we showed that NIr treatment influenced the glial response, particularly that of the astrocytes, in our monkey MPTP model of Parkinson’s disease. Our findings raise the possibility of glial cells as a future therapeutic target using NIr.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- ATP:
-
Adenosine triphosphate
- GFAP:
-
Glial fibrillary acidic protein
- GP:
-
Globus pallidus
- IBA1:
-
Ionised calcium-binding adaptor molecule 1
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- NIr:
-
Near-infrared light
- R:
-
Red nucleus
- SNc:
-
Substantia nigra pars compacta
- SNr:
-
Substantia nigra pars reticulata
References
Ashkan K, Wallace BA, Mitrofanis J et al (2007) SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson’s disease. Parkinsonism Relat Disord 13:266–275. doi:10.1016/j.parkreldis.2006.10.009
Barcia C, Barreiro AF, Poza M, Herrero M-T (2003) Parkinson’s disease and inflammatory changes. Neurotox Res 5:411–417. doi:10.1007/BF03033170
Begum R, Powner MB, Hudson N et al (2013) Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model. PLoS ONE 8:e57828. doi:10.1371/journal.pone.0057828
Bergman H, Deuschl G (2002) Pathophysiology of Parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov Disord 17(Suppl 3):S28–S40
Blandini F, Nappi G, Tassorelli C, Martignoni E (2000) Functional changes of the basal ganglia circuitry in Parkinson’s disease. Prog Neurobiol 62:63–88
Burda JE, Bernstein AM, Sofroniew MV (2016) Astrocyte roles in traumatic brain injury. Exp Neurol 275(Pt 3):305–315. doi:10.1016/j.expneurol.2015.03.020
Chung H, Dai T, Sharma SK et al (2012) The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng 40:516–533. doi:10.1007/s10439-011-0454-7
Członkowska A, Kohutnicka M, Kurkowska-Jastrzebska I, Członkowski A (1996) Microglial reaction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinson’s disease mice model. Neurodegeneration 5:137–143
Darlot F, Moro C, El Massri N et al (2016) Near-infrared light is neuroprotective in a monkey model of Parkinson disease. Ann Neurol 79:59–75. doi:10.1002/ana.24542
El Massri N, Johnstone DM, Peoples CL et al (2016) The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice. Int J Neurosci 126:76–87. doi:10.3109/00207454.2014.994063
Fernagut PO, Diguet E, Bioulac B, Tison F (2004) MPTP potentiates 3-nitropropionic acid-induced striatal damage in mice: reference to striatonigral degeneration. Exp Neurol 185:47–62
Francis JW, Von Visger J, Markelonis GJ, Oh TH (1995) Neuroglial responses to the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse striatum. Neurotoxicol Teratol 17:7–12. doi:10.1016/0892-0362(94)00048-I
Gkotsi D, Begum R, Salt T et al (2014) Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP. Exp Eye Res 122:50–53. doi:10.1016/j.exer.2014.02.023
Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26:6–17. doi:10.1002/mds.23455
Hamby ME, Sofroniew MV (2010) Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7:494–506. doi:10.1016/j.nurt.2010.07.003
Hurley SD, O’Banion MK, Song DD et al (2003) Microglial response is poorly correlated with neurodegeneration following chronic, low-dose MPTP administration in monkeys. Exp Neurol 184:659–668. doi:10.1016/S0014-4886(03)00273-5
Johnstone DM, El Massri N, Moro C et al (2014) Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism—an abscopal neuroprotective effect. Neuroscience 274:93–101. doi:10.1016/j.neuroscience.2014.05.023
Khan I, Arany P (2015) Biophysical approaches for oral wound healing: emphasis on photobiomodulation. Adv Wound Care (New Rochelle) 4:724–737. doi:10.1089/wound.2014.0623
Khuman J, Zhang J, Park J et al (2012) Low-level laser light therapy improves cognitive deficits and inhibits microglial activation after controlled cortical impact in mice. J Neurotrauma 29:408–417. doi:10.1089/neu.2010.1745
Kohutnicka M, Lewandowska E, Kurkowska-Jastrzȩbska I et al (1998) Microglial and astrocytic involvement in a murine model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 39:167–180. doi:10.1016/S0162-3109(98)00022-8
McGeer PL, McGeer EG (1998) Glial cell reactions in neurodegenerative diseases: pathophysiology and therapeutic interventions. Alzheimer Dis Assoc Disord 12(Suppl 2):S1–S6
McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483. doi:10.1002/mds.21751
McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291
McGeer PL, Schwab C, Parent A, Doudet D (2003) Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol 54:599–604. doi:10.1002/ana.10728
Mirza B, Hadberg H, Thomsen P, Moos T (1999) The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson’s disease. Neuroscience 95:425–432. doi:10.1016/S0306-4522(99)00455-8
Moro C, El Massri N, Torres N et al (2014) Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice. J Neurosurg 120:670–683. doi:10.3171/2013.9.JNS13423
Muili KA, Gopalakrishnan S, Meyer SL et al (2012) Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light. PLoS ONE 7:e30655. doi:10.1371/journal.pone.0030655
Paxinos G, Huang X, Toga A (1998) The Rhesus monkey brain in stereotaxic coordinates. Academic Press, USA
Pekny M, Pekna M (2014) Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev 94:1077–1098. doi:10.1152/physrev.00041.2013
Pekny M, Wilhelmsson U, Pekna M (2014) The dual role of astrocyte activation and reactive gliosis. Neurosci Lett 565:30–38. doi:10.1016/j.neulet.2013.12.071
Peoples C, Spana S, Ashkan K et al (2012) Photobiomodulation enhances nigral dopaminergic cell survival in a chronic MPTP mouse model of Parkinson’s disease. Parkinsonism Relat Disord 18:469–476. doi:10.1016/j.parkreldis.2012.01.005
Reinhard JF Jr, Miller DB, O’Callaghan JP (1988) The neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) increases glial fibrillary acidic protein and decreases dopamine levels of the mouse striatum: evidence for glial response to injury. Neurosci Lett 95:246–251
Reinhart F, El Massri N, Darlot F et al (2015) Evidence for improved behaviour and neuroprotection after intracranial application of near infrared light in a hemi-parkinsonian rat model. J Neurosurg 27:1–13
Rojas J, Gonzalez-Lima F (2011) Low-level light therapy of the eye and brain. Eye Brain 3:49–67
Rutar M, Natoli R, Chia RX et al (2015) Chemokine-mediated inflammation in the degenerating retina is coordinated by Müller cells, activated microglia, and retinal pigment epithelium. J Neuroinflammation 12:8. doi:10.1186/s12974-014-0224-1
Schneider JS, Gonczi H, Decamp E (2003) Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms. Brain Res 990:38–44
Shaw VE, Spana S, Ashkan K et al (2010) Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment. J Comp Neurol 518:25–40. doi:10.1002/cne.22207
Strömberg I, Björklund H, Dahl D et al (1986) Astrocyte responses to dopaminergic denervations by 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as evidenced by glial fibrillary acidic protein immunohistochemistry. Brain Res Bull 17:225–236. doi:10.1016/0361-9230(86)90119-X
Verkhratsky A, Parpura V, Pekna M et al (2014) Glia in the pathogenesis of neurodegenerative diseases. Biochem Soc Trans 42:1291–1301. doi:10.1042/BST20140107
Wallace BA, Ashkan K, Heise CE et al (2007) Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys. Brain 130:2129–2145. doi:10.1093/brain/awm137
Acknowledgments
We are forever grateful to Michael J Fox Foundation, Credit Agricole Sud Rhones Alpes, Fondation Philanthropique Edmond J Safra, France Parkinson and the French National Research Agency (ANR Carnot Institute), Tenix corp and Salteri family and our industry partners for funding this work. Daniel Johnstone is an Early Career Fellow of the NHMRC, Australia. We thank Sharon Spana, Diane Agay, Guillaume Barboux, Clément Perrin, Cyril Zenga and Mylène D’Orchymont for excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
El Massri, N., Moro, C., Torres, N. et al. Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys. Exp Brain Res 234, 3225–3232 (2016). https://doi.org/10.1007/s00221-016-4720-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00221-016-4720-7