Hydrogen sulfide slows down progression of experimental Alzheimer’s disease by targeting multiple pathophysiological mechanisms

Giuliani, Daniela; Ottani, Alessandra; Zaffe, Davide; Galantucci, Maria; Strinati, Flavio; Lodi, Renzo; Guarini, Salvatore

doi:10.1016/j.nlm.2013.05.006

Cited by 225 publications

(117 citation statements)

References 49 publications

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“…Furthermore, it has been reported that brain H 2 S synthesis is severely decreased in AD patients (up to 55%) [20], and plasma H 2 S levels are negatively correlated with the severity of AD [21]. Recently, it has been demonstrated that H 2 S donor sodium hydrosulfide reduces Aβ generation in cultured cells and subsequently, we have demonstrated this reduction also in vivo experiments with improvement of cognitive performance in rats and transgenic mice with mild (early stage) AD [22]. This study focuses on the possible ability of a chronic treatment (3 months) with an H 2 S donor and a sulfurous water, with high content in H 2 S [23], to counteract the progression also in a severe (late stage) AD, at different ages (6 and 12 months).…”

Section: Mechanisms Of Hydrogensupporting

confidence: 58%

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

et al. 2018

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Backgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H₂S), is decreased in the brain of Alzheimer’s disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H₂S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H₂S injections are neuroprotective in an early phase of preclinical AD. Objectives: This study focuses on the possible neuroprotection of a chronic treatment with an H₂S donor and sulfurous water (rich of H₂S) in a severe transgenic 3×Tg-AD mice model. Method: 3×Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H₂S donor and sulfurous water (rich of H₂S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid/tau cascade, excitotoxic, inflammatory and apoptotic responses. Results: Three months of treatments with H₂S significantly protected against impairment in learning and memory in a severe 3×Tg-AD mice model, at both ages studied, and reduced the size of Amyloid β plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. Conclusion: Our findings indicate that appropriate treatments with various sources of H₂S, might represent an innovative approach to counteract early and severe AD progression in humans.

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Section: Mechanisms Of Hydrogensupporting

confidence: 58%

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

et al. 2018

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“…The H 2 S donors include sulfide salts such as sodium sulfide (Na 2 S) and NaHS, garlic-derived compounds, and 1,2-dithiole-3-thiones [44]. Among these donors, NaHS has been widely used in neurodegenerative diseases such as Parkinson’s disease (PD) and AD, and the concentration used in this study was selected according to previous results and other references [45, 46]. CBS mediates H 2 S biosynthesis in the central nervous system of db/db mice, and there are several ways for CBS to generate H 2 S [17].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

Zhong

et al. 2017

Cell Physiol Biochem

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Background: Diabetes-associated cognitive decline (DACD) is one of the complications of diabetes and leads to cognitive impairment and an increased risk of dementia. However, the exact mechanism of DACD has not been fully characterized, and a successful therapy for this issue has not been established. This study aimed to detect the anti-apoptotic and anti-inflammatory effects of hydrogen sulfide (H₂S) on DACD. Methods: We used a behavioural scoring method, Western blot, TUNEL staining and immunofluorescence staining to investigate the expression of the mitochondrial apoptotic pathway and the IL-23/IL-17 axis in db/db mice with or without sodium hydrosulfide (NaHS) administration. Results: NaHS administration mice exhibited reduced time to find the platform and a shorter swimming distance (P<0.05), while the time spent in the target quadrant was increased compared to that of the db/db group (P<0.05). Pro-apoptotic proteins, including cleaved Caspase-3, cleaved Caspase-9, Bax and cytochrome C, were elevated in the db/db group (P<0.01) but were downregulated in the db/db+NaHS group (P<0.05). Exogenous H₂S decreased the numbers of TUNEL-positive cells in the db/db mice (P<0.05). The Western blot analysis showed that the expression levels of IL-23/IL-17 were lower in the NaHS administration group than in the db/db group (P<0.05). Conclusion: We demonstrated that H₂S improved the spatial learning and memory abilities of the db/db mice by modulating the mitochondrial apoptotic pathway and the IL-23/IL-17 axis, which were found to be associated with DACD. H₂S treatment may help prevent the progression of apoptotic hippocampal neurons in db/db mice and inform the development of a new therapeutic target.

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“…H 2 S shares similar features with NO, and CO, and play important vasodilatatory and antiatherosclerotic roles [216][217][218] . These cytoprotective actions may at least partly explain H 2 S beneficial effects in slowing down progression of experimental Alzheimer's disease [219] , as well as improving health in major cardiovascular diseases [220] . It was recently suggested that atherosclerosis and Alzheimer are diseases with a common cause [221] , and it seems that chronic T. gondii infection may be at least in part responsible for this causal relationship [222,223] .…”

Section: Important Role Of Acat1 In Foam Cells Formation and Developmmentioning

confidence: 99%

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

Prandota

2017

Journal of Cardiology and Therapy

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Hydrogen sulfide slows down progression of experimental Alzheimer’s disease by targeting multiple pathophysiological mechanisms

Cited by 225 publications

References 49 publications

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

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