Ann Pharmacol Pharm | Volume 1, Issue 1 | Research Article | Open Access

Serotonin-1A Agonist 8-OH-DPAT Alleviates Motor Dysfunction and Motor Neuron Degeneration in a Model of Amyotrophic Lateral Sclerosis

Ikuko Miyazaki1*, Shinki Murakami1, Takashi Nakano2, Nao Torigoe2, Ryo Kikuoka2, Yoshihisa Kitamura2, Toshiaki Sendo2 and Masato Asanuma1

1Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
2Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

*Correspondance to: Ikuko Miyazaki 

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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.

Keywords:

Amyotrophic lateral sclerosis; Motor neurons; Serotonin 1A agonist; 8-OH-DPAT; Astrocyte; Metallothionein

Citation:

Miyazaki I, Murakami S, Nakano T, Torigoe N, Kikuoka R, Kitamura Y, et al. Serotonin-1A Agonist 8-OH-DPAT Alleviates Motor Dysfunction and Motor Neuron Degeneration in a Model of Amyotrophic Lateral Sclerosis. Ann Pharmacol Pharm. 2016; 1(1): 1003.

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