Abstract :Abstract
Glutaminergic excitotoxicity, oxidative stress, and inflammation are related to the pathogenesis of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by selective loss of upper and lower motor neurons, progressive paralysis, and muscle atrophy. We previously reported that 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), a serotonin 1A (5-HT1A) receptor full agonist, can induce astrocyte proliferation and upregulate antioxidative molecules such as metallothionein (MT) in astrocytes, and that the treatment with 8-OH-DPAT protected dopaminergic neurons in parkinsonian mice. In the present study, we examined whether 8-OH-DPAT shows neuroprotective effects in the mutant superoxide dismutase-1 (SOD1) transgenic ALS model mice (G93A–SOD1 mice). Treatment with 8-OH-DPAT attenuated motor neuronal loss in the spinal cord, and slowed progression of motor dysfunction, which was evaluated by the hanging test, rotarod test, and extension reflex test in G93A–SOD1 mice. Moreover, 8-OHDPAT administration markedly increased the MT expression in astrocytes in the ventral horn of spinal cord in G93A–SOD1 mice. These results suggest that the treatment with a 5-HT1A agonist, such as 8-OH-DPAT, is a possible therapeutic strategy against progressive neurodegeneration in ALS.