Chemotherapy delays progression of motor neuron disease in the SOD1 G93A transgenic mouse.
BACKGROUND
A significant proliferation of glial cells occurs in the spinal cord and brainstem of SOD1 G93A transgenic mice with familial amyotrophic lateral sclerosis (ALS). Since activated glia may contribute to motor neuron degeneration, we tested whether inhibition of gliosis using low-dose chemotherapy is beneficial in this mouse model.


METHODS
Mice were administered fortnightly intraperitoneal injections of 0.1 mg/kg vincristine (VIN) or saline commencing at postnatal day 68 before disease onset. Mice were sacrificed at end-stage disease, and spinal cords were examined for histology.


RESULTS
Survival of VIN-treated mice was significantly increased at 132.0 +/- 4.1 days compared to control animals at 117.8 +/- 2.1 days (p < 0.05). Furthermore, analysis of microglia and astrocyte populations suggests a reduction in the former following VIN therapy.


CONCLUSIONS
This study suggests that chemotherapy may offer an alternative therapy or co-therapy for ALS.
Bruce
K M
KM
Department of Anatomy and Cell Biology, Monash University, Melbourne, Australia.
Narayan
K
K
Kong
H C
HC
Larmour
I
I
Lopes
E C
EC
Turner
B J
BJ
Bertram
J F
JF
Cheema
S S
SS
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D037121:Plant Lectins / Q000032:analysis; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D005904:Glial Fibrillary Acidic Protein; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; D014750:Vincristine; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase