Hippocampal Glutathione Depletion and pH Increment in Alzheimer’s Disease: An in vivo MRS Study

2021 ◽  
pp. 1-13
Author(s):  
Deepika Shukla ◽  
Pravat K. Mandal ◽  
Ritwick Mishra ◽  
Khushboo Punjabi ◽  
Divya Dwivedi ◽  
...  

Background: Oxidative stress plays a major role in Alzheimer’s disease (AD) pathogenesis, and thus, antioxidant glutathione (GSH) has been actively investigated in mitigating the oxidative load. Significant hippocampal GSH depletion has been correlated with cognitive impairment in AD. Furthermore, postmortem studies indicated alterations in cellular-energy metabolism and hippocampal pH change toward alkalinity in AD. Objective: Concurrent analysis of hippocampal GSH and pH interplay in vivo on the same individual is quite unclear and hence requires investigation to understand the pathological events in AD. Methods: Total 39 healthy old (HO), 22 mild cognitive impairment (MCI), and 37 AD patients were recruited for hippocampal GSH using 1H-MRS MEGA-PRESS and pH using 2D 31P-MRSI with dual tuned (1H/31P) transmit/receive volume head coil on 3T-Philips scanner. All MRS data processing using KALPANA package and statistical analysis were performed MedCalc, respectively and NINS-STAT package. Results: Significant GSH depletion in the left and right hippocampus (LH and RH) among MCI and AD study groups as compared to HO was observed, whereas pH increased significantly in the LH region between HO and AD. Hippocampal GSH level negatively correlated with pH in both patient groups. The ROC analysis on the combined effect of GSH and pH in both hippocampal regions give accuracy for MCI (LH: 78.27%; RH: 86.96%) and AD (LH: 88%; RH: 78.26%) groups differentiating from HO. Conclusion: Outcomes from this study provide further insights to metabolic alterations in terms of concurrent assessment of hippocampal GSH and pH levels in AD pathogenesis, aiding in early diagnosis of MCI and AD.

2012 ◽  
Vol 31 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Yanyong Liu ◽  
Haji Akber Aisa ◽  
Chao Ji ◽  
Nan Yang ◽  
Haibo Zhu ◽  
...  

Aging-associated cognitive impairment is an important health care issue since individuals with mild cognitive impairment are more likely to develop Alzheimer’s disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment associated with aging were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70, and 140 mg/kg exerted an improved effect on the learning and memory impairment in aged rats. Subsequently, GHE afforded a beneficial action on eradication of free radicals without influence on the activity of glutathione peroxidase and superoxide dismutase. GHE treatment enhanced the expression levels of nerve growth factor. Meanwhile, proliferation of neural progenitor cells was elevated in hippocampus after treatment with GHE. Taken together, neurogenic niche improvement could be involved in the mechanism underlying neuroprotection of GHE against aging-associated cognitive impairment. These findings suggested that GHE might be a potential agent as cognitive-enhancing drugs that delay or halt mild cognitive impairment progression to Alzheimer’s disease or treatment of aging-associated cognitive impairment.


Author(s):  
James B. Brewer ◽  
Jorge Sepulcre ◽  
Keith A. Johnson

Advances in quantitative structural, functional, and molecular neuroimaging have provided new tools for objective, in vivo, assessment of critical aspects of Alzheimer’s disease and other neurodegenerative disorders. Measures of brain atrophy or brain dysfunction, coupled with measures of disease-linked pathology, might complement the history, physical and neurocognitive evaluation of patients and thereby improve predictive prognosis, especially at early stages of cognitive impairment where neurodegenerative etiology is less certain. Such imaging biomarkers are currently used in nearly all clinical trials of therapeutic agents for Alzheimer’s disease and are increasingly incorporated into clinical practice. In this chapter, imaging biomarkers are introduced and discussed to familiarize the reader with their potential research and clinical uses.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Joaquín G. Cordero ◽  
Ramón García-Escudero ◽  
Jesús Avila ◽  
Ricardo Gargini ◽  
Vega García-Escudero

Alzheimer’s disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β-amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer’s patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer’s patients. The benefits of the Mediterranean diet on Alzheimer’s disease and cognitive impairment are well known, attributing this effect to several polyphenols, such as oleuropein aglycone (OLE), present in extra virgin olive oil. OLE is able to induce autophagy, achieving a decrease of aggregated proteins and a reduction of cognitive impairment in vivo. This effect is caused by the modulation of several pathways including the AMPK/mTOR axis and the activation of autophagy gene expression mediated by sirtuins and histone acetylation or EB transcription factor. We propose that supplementation of diet with extra virgin olive oil might have potential benefits for Alzheimer’s patients by the induction of autophagy by OLE.


2012 ◽  
Vol 31 (s3) ◽  
pp. S137-S154 ◽  
Author(s):  
Takao Yamasaki ◽  
Shizuka Horie ◽  
Hiroyuki Muranaka ◽  
Yumiko Kaseda ◽  
Yasuyo Mimori ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin Gyu Choi ◽  
Sun Yeou Kim ◽  
Jong Woo Kim ◽  
Myung Sook Oh

Alzheimer’s disease (AD), the most common form of dementia, is an age-related neurodegenerative disease that is characterized by memory dysfunction, neuronal cell damage, and neuroinflammation. It is believed that AD-related pathology is mostly due to the overproduction of Aβ, especially the oligomeric form (AβO), in the brain. Evidence of the effects of multifunctional medicinal herbs in the treatment of AD has been steadily increasing. Optimized-SopungSunkiwon (OSS), a multiherbal formulation that is composed of six medicinal herbs derived from SopungSunkiwon, is a traditional medicine that is prescribed for neurodegenerative disorders in elderly patients. We previously reported that OSS showed an antiamnesic and memory enhancing effect in mice, but it is unknown whether OSS has a protective effect against AβO neurotoxicity. In this study, we investigated the effects of OSS in AD models induced by AβOin vitroandin vivo. We found that OSS protected neuronal cells and inhibited the generation of nitric oxide and reactive oxygen species against AβO toxicityin vitro. These results were confirmed byin vivodata that oral administration of OSS for 14 days attenuated memory impairments and neuronal cell death by modulating gliosis, glutathione depletion, and synaptic damage in the mouse hippocampus induced by AβO.


2017 ◽  
Vol 13 (7S_Part_15) ◽  
pp. P760-P761
Author(s):  
Elijah Mak ◽  
Silvy Gabel ◽  
Simon Cervenka ◽  
Li Su ◽  
Ajenthan Surendranathan ◽  
...  

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