Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice

Abstract

We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100–250 mg/kg) or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30–45%) the increase in Fos+ cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice

“…Our experimental paradigm of the simultaneous administration of parkinsonian insult and treatment was similar to that in previous animal models of Parkinson disease. 23,25,33,37,38,43 This paradigm is unlike the clinical reality in which there is cell loss prior to therapeutic intervention; however, in our experimental study we hoped to determine the maximum effect of any NIr neuroprotection provided via the LED-optical fiber implant.…”

“…23,25,37,38 At 15 minutes and 6 hours after each injection, the LED was turned on in the mice in some of the experimental groups. In the Saline-pNIr and MPTP-pNIr groups, the LED was turned on for a 90-second pulse (same duration as in previous studies using the external WARP-LED apparatus), 25,32,37,38 whereas in the Saline-cNIr and MPTP-cNIr groups, the LED was turned on and left on until the end of the experimental period (6 days). Following the experimental period, the mice were anesthetized, and their brains (midbrain sections including the SNc) were processed for TH immunocytochemistry as described above.…”

“…25,32,38 In terms of analysis, the number of TH+ cells within the SNc was estimated using the optical fractionator method (StereoInvestigator, MBF Science), as outlined previously. 23,25,32,37,38,43 Briefly, systematic random sampling of sites-with an unbiased counting frame (100 × 100 μm)-within defined boundaries of the SNc was undertaken. Counts were made from every second section, and for consistency, the right side of the brain was counted in all cases.…”

“…In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, NIr protects many dopaminergic cells in the substantia nigra pars compacta (SNc) from degeneration 32,38 and restores functional activity of the subthalamic nucleus and zona incerta (key basal ganglia nuclei) to near control levels. 37 Further, NIr treatment recovers various parameters of locomotive behavior, for example, mobility and velocity, in MPTP-treated mice. 25,44 Moreover, in transgenic mice expressing the A53T human a-synuclein mutation, NIr treatment delays disease progression and reduces the severity of the disease phenotype.…”

Near infrared light mitigates cerebellar pathology in transgenic mouse models of dementia

“…For example, NIr treatment has yielded beneficial outcomes in models of retinal damage [1,2], traumatic brain injury [3][4][5], Parkinson's disease [6][7][8][9] and Alzheimer's disease (AD) [10,11] and in clinical trials on patients suffering macular degeneration [12] and stroke [13].…”