title: The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice.
abstract: We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice received MPTP injections (50 mg/kg) and 2 J/cm2 NIr dose with either 2 d or 7 d survival period. In another series, with a longer 14 d survival period, mice had a stronger MPTP regime (100 mg/kg) and either 2 J/cm2 or 4 J/cm2 NIr dose. Brains were processed for routine immunohistochemistry and cell counts were made using stereology. Our findings were that in the 2 d series, no change in SNc TH+ cell number was evident after any treatment. In the 7 d series however, MPTP insult resulted in ∼45% reduction in TH+ cell number; after NIr (2 J/cm2) treatment, many cells were protected from the toxic insult. In the 14 d series, MPTP induced a similar reduction in TH+ cell number. NIr mitigated the loss of TH+ cells, but only at the higher dose of 4 J/cm2; the lower dose of 2 J/cm2 had no neuroprotective effect in this series. The higher dose of NIr, unlike the lower dose, also mitigated the MPTP- induced increase in CPu astrocytes after 14 d; these changes were independent of TH+ terminal density, of which, did not vary across the different experimental groups. In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr were required to protect cells and reduce astrogliosis.
authors.affiliation: a Department of Anatomy F13, University of Sydney, Australia.
authors.forename: Nabil
authors.initials: N
authors.lastname: El Massri
authors.affiliation: b Department of Physiology F13, University of Sydney, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Johnstone
authors.affiliation: a Department of Anatomy F13, University of Sydney, Australia.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Peoples
authors.affiliation: c University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, Grenoble, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Moro
authors.affiliation: c University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, Grenoble, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Reinhart
authors.affiliation: c University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, Grenoble, France.
authors.forename: Napoleon
authors.initials: N
authors.lastname: Torres
authors.affiliation: b Department of Physiology F13, University of Sydney, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
authors.affiliation: c University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, Grenoble, France.
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
authors.affiliation: a Department of Anatomy F13, University of Sydney, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Mitrofanis
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000528:radiation effects; D002421:Caudate Nucleus / Q000473:pathology / Q000528:radiation effects; D002452:Cell Count; D002470:Cell Survival / Q000528:radiation effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005911:Gliosis / Q000473:pathology / Q000532:radiotherapy*; D007259:Infrared Rays / Q000627:therapeutic use*; D028022:Low-Level Light Therapy; D020267:MPTP Poisoning / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000032:analysis; D020734:Parkinsonian Disorders / Q000473:pathology / Q000532:radiotherapy*; D065842:Pars Compacta / Q000473:pathology / Q000528:radiation effects*; D011699:Putamen / Q000473:pathology / Q000528:radiation effects; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D009419:Nerve Tissue Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
keywords: neuroprotection; substantia nigra; tyrosine hydroxylase