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Transcorneal electrical stimulation enhances cognitive functions in aged and 5XFAD mouse models

Yu WS, Aquili L, Wong KH, Lo ACY, Chan LLH, Chan YS, et al.

Ann N Y Acad Sci, 2022 09;1515(1):249-265.
PMID: 35751874 DOI: 10.1111/nyas.14850

Dementia is a major burden on global health for which there are no effective treatments. The use of noninvasive visual stimulation to ameliorate cognitive deficits is a novel concept that may be applicable for treating dementia. In this study, we investigated the effects of transcorneal electrical stimulation (TES) on memory enhancement using two mouse models, in aged mice and in the 5XFAD model of Alzheimer's disease. After 3 weeks of TES treatment, mice were subjected to Y-maze and Morris water maze tests to assess hippocampal-dependent learning and memory. Immunostaining of the hippocampus of 5XFAD mice was also performed to examine the effects of TES on amyloid plaque pathology. The results showed that TES improved the performance of both aged and 5XFAD mice in memory tests. TES also reduced hippocampal plaque deposition in male, but not female, 5XFAD mice. Moreover, TES significantly reversed the downregulated level of postsynaptic protein 95 in the hippocampus of male 5XFAD mice, suggesting the effects of TES involve a postsynaptic mechanism. Overall, these findings support further investigation of TES as a potential treatment for cognitive dysfunction and mechanistic studies of TES effects in other dementia models.
Fulltext The Monkey Head Mushroom and Memory Enhancement in Alzheimer's Disease

Yanshree, Yu WS, Fung ML, Lee CW, Lim LW, Wong KH

Cells, 2022 Jul 24;11(15).
PMID: 35892581 DOI: 10.3390/cells11152284

Alzheimer's disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD.
Fulltext Neuroprotective Effects and Therapeutic Potential of Transcorneal Electrical Stimulation for Depression

Yu WS, Kwon SH, Agadagba SK, Chan LL, Wong KH, Lim LW

Cells, 2021 09 21;10(9).
PMID: 34572141 DOI: 10.3390/cells10092492

Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.
Fulltext Malaysian brown macroalga Padina australis mitigates lipopolysaccharide-stimulated neuroinflammation in BV2 microglial cells

Subermaniam K, Lew SY, Yow YY, Lim SH, Yu WS, Lim LW, et al.

Iran J Basic Med Sci, 2023;26(6):669-679.
PMID: 37275754 DOI: 10.22038/IJBMS.2023.67835.14842

OBJECTIVES: Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells.
MATERIALS AND METHODS: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells.
RESULTS: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5-2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid.
CONCLUSION: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.