Light therapy and supplementary Riboflavin in the SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis (FALS).
OBJECTIVE
Familial amyotrophic lateral sclerosis (FALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and death. Mitochondrial dysfunction and oxidative stress play an important role in motor neuron loss in ALS. Light therapy (LT) has biomodulatory effects on mitochondria. Riboflavin improves energy efficiency in mitochondria and reduces oxidative injury. The purpose of this study was to examine the synergistic effect of LT and riboflavin on the survival of motor neurons in a mouse model of FALS.


METHODS
G93A SOD1 transgenic mice were divided into four groups: Control, Riboflavin, Light, and Riboflavin+Light (combination). Mice were treated from 51 days of age until death. A single set of LT parameters was used: 810 nm diode laser, 140-mW output power, 1.4 cm(2) spot area, 120 seconds treatment duration, and 12 J/cm(2) energy density. Behavioral tests and weight monitoring were done weekly. At end stage of the disease, mice were euthanized, survival data was collected and immunohistochemistry and motor neuron counts were performed.


RESULTS
There was no difference in survival between groups. Motor function was not significantly improved with the exception of the rotarod test which showed significant improvement in the Light group in the early stage of the disease. Immunohistochemical expression of the astrocyte marker, glial fibrilary acidic protein, was significantly reduced in the cervical and lumbar enlargements of the spinal cord as a result of LT. There was no difference in the number of motor neurons in the anterior horn of the lumbar enlargement between groups.


CONCLUSIONS
The lack of significant improvement in survival and motor performance indicates study interventions were ineffective in altering disease progression in the G93A SOD1 mice. Our findings have potential implications for the conceptual use of light to treat other neurodegenerative diseases that have been linked to mitochondrial dysfunction.
Moges
Helina
H
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Vasconcelos
Olavo M
OM
Campbell
William W
WW
Borke
Rosemary C
RC
McCoy
Jennifer Anne
JA
Kaczmarczyk
Lauren
L
Feng
Ji
J
Anders
Juanita J
JJ
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000209:etiology / Q000532:radiotherapy*; D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D054023:Lasers, Semiconductor / Q000627:therapeutic use*; D028022:Low-Level Light Therapy; D051379:Mice; D008822:Mice, Transgenic; D012256:Riboflavin / Q000627:therapeutic use*; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014803:Vitamin B Complex / Q000627:therapeutic use*
D014803:Vitamin B Complex; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D012256:Riboflavin