ABSTRACT
Diallyl trisulfide (DATS) is one of the major constituents in garlic oil and has been documented to transcriptionally activate phase II enzymes. The purpose of this study is to evaluate the effects of DATS in prolonging disease duration and survival in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). SOD1-G93A transgenic mice were randomly divided into DATS-treated group (80mg/kg/d, p.o.) and vehicle-treated group at disease onset stage. Oral administration of DATS beginning at clinical onset stage significantly prolonged disease duration and extended life span for about one week. DATS treatment induced HO-1 and reduced GFAP expression in the lumbar spinal cord of SOD1-G93A transgenic mice. This study indicates that DATS has multifunctional neuroprotective effects in SOD1-G93A transgenic mice.
Subject(s)
Allyl Compounds/therapeutic use , Amyotrophic Lateral Sclerosis/enzymology , Amyotrophic Lateral Sclerosis/prevention & control , Disease Models, Animal , Neuroprotective Agents/therapeutic use , Sulfides/therapeutic use , Superoxide Dismutase/biosynthesis , Amyotrophic Lateral Sclerosis/genetics , Animals , Female , Garlic , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oils , Random Allocation , Superoxide Dismutase/geneticsABSTRACT
The SOD1-G93A transgenic mouse is a widely used ALS model, but the death of lower motor neurons is the hallmark. Here, we show that the SOD1-G93A transgene and HO-1 are preferentially over-expressed in the lumbar spinal cord, particularly in the activated astrocytes of the transgenic mice. We also show down-regulation of GLT-1 in spite of the proliferating astrocytes. However, GLT-1, SOD1-G93A transgene and HO-1 expression were not obviously changed in the motor cortex. Our data link spinal cord vulnerability to relatively decreased expression of GLT-1, and high expression of the transgene and HO-1 in astrocytes in SOD1-G93A transgenic mice.
