Hydrogen sulfide functions as a neuromodulator to regulate striatal neurotransmission in a mouse model of Parkinson's disease.
Hydrogen sulfide (H2S), a novel endogenous gasotransmitter, has been considered a neuromodulator to enhance hippocampal long-term potentiation and exerts neuroprotective effects against neurotoxin-induced neurodegeneration in rodent models of Parkinson's disease (PD). However, whether H2S can function as a neuromodulator to regulate the levels of nigrostriatal neurotransmitters and then impact the vulnerability of dopaminergic (DA) neurons in response to neurotoxins remains unknown. For this study, we prepared a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine plus probenecid (MPTP/p)-induced mouse subacute model of PD to explore the modulatory effect of H2S on monoamine and amino acid neurotransmitters in the striatum of MPTP-treated mice. This study shows that NaHS (an H2S donor, 5.6 mg/kg/day, i.p.) administration improves the survival rate and significantly ameliorates the weight loss of MPTP-treated mice. NaHS treatment attenuated MPTP-induced neuronal damage, restored the diminution of DA neurons, and suppressed the overactivation of astrocytes in the mouse striatum. Additionally, NaHS upregulated striatal serotonin levels and modulated the balance of excitatory glutamate and the inhibitory γ-aminobutyric acid system in response to MPTP challenge. The current study indicates that H2S may function as an effective neuromodulator to regulate striatal neurotransmission and provides insight into the potential of H2S for PD therapy.
Department of Geriatric Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Min
M
Wang
Jun
J
Zhu
Yang
Y
Pan
Jingde
J
Dong
Lili
L
Zhang
Xiangrong
X
Zhang
Li
L
Zhang
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D020734:Parkinsonian Disorders / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D013440:Sulfides; D012701:Serotonin; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
Parkinson's disease; amino acid neurotransmitter; hydrogen sulfide; monoamine; striatum