Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-Induced Experimental Model of ALS

Minj, Elizabeth; Upadhayay, Shubham; Mehan, Sidharth

doi:10.1007/s11064-021-03366-2

Cited by 48 publications

(45 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, demyelination in experimental rats was induced by chronic oral administration of methylmercury for three weeks (Minj et al, 2021, Alam et al, 2020. Pre-clinically, MeHg is a potent neurotoxin that induces neuro-cognitive de cits, mimicking an experimental animal model of ALS.…”

Section: Introductionmentioning

confidence: 68%

“…In the present research, the MeHg intoxication-induced experimental rat model was used to study the pathological alterations similar to ALS. Evidence from different animal studies suggests that MeHg exposure may contribute to ALS progression (Minj et al, 2021, Alam et al, 2020, Praline et al, 2007.…”

Section: Discussionmentioning

confidence: 99%

“…The MeHg-induced experimental model of ALS in rats was established according to the method validated by (Alam et al, 2020, Minj et al, 2021. Experimental rats were administered with MeHg orally at 5 mg/kg for three consecutive weeks.…”

Section: Experimental Animal Model Of Methylmercury-induced Als-like Ratsmentioning

confidence: 99%

“…Similarly, GLP-1 levels were also assessed in brain homogenate (Candeias et al, 2018) and CSF obtained from rats. Furthermore, the level of myelin basic protein (MBP) was measured in rat brain homogenate (Minj et al, 2021) and CSF samples (Ohta et al, 2002). The levels of IGF-1 and GLP-1 proteins in brain homogenate and CSF were represented as pg/mg protein and ng/ml protein, respectively.…”

Section: Assessment Of Cellular and Molecular Markersmentioning

confidence: 99%

“…The volume of the demyelinated region (mm 3 ) for each brain segment was estimated from the greyish region around the striatum. In each coronal segment, the extent of white matter degeneration was determined by calculating the demyelination volume (length×breadth×height) (Minj et al, 2021).…”

Section: Assessment Of Oxidative Stress Markersmentioning

confidence: 99%

See 4 more Smart Citations

IGF-1/GLP-1 Signaling Activator 4-hydroxyisoleucine (4-HI) Prevent Neurobehavioral and Neurochemical Defects in Methylmercury-induced Experimental Model of ALS: Insights From CSF, Blood Plasma and Brain Homogenate Samples in Rats

Shandilya

Mehan

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is the most prevalent adult motor neuron disease, characterized by progressive neuromuscular atrophy, heterogeneous muscle wasting, weakness, and behavioural despair-like symptoms, which are frequently associated with cognitive impairments. The neuropathological hallmarks of MeHg-induced ALS include oligodendrocyte destruction, myelin basic protein (MBP) depletion, and white matter degeneration, which ultimately leads to demyelination and motor neuron death. Numerous research studies have demonstrated that IGF-1/GLP-1 signaling dysregulation plays a significant role in ALS progression as it triggers programmed neuronal cell death, myelin sheath destruction, demyelination, glutamate excitotoxicity, pro-inflammatory cytokine release, and neuroinflammation. 4-hydroxyisoleucine (4-HI) is a unique bioactive amino acid derived from Trigonella foenum graecum, with insulin-mimetic and insulin-sensitizing properties in animal models. The objective of this study was to explore the neuroprotective potential of 4-HI on behavioural, molecular, neurochemical, and gross pathological alterations in MeHg-treated ALS-like rats, with a particular focus on its influence on IGF-1/GLP-1 upregulation in the brain. Furthermore, we investigated the effect of 4-HI on the concentration of myelin basic protein (MBP) in rat brain homogenate and CSF, and specific cell death markers such as caspase-3, Bax, and Bcl-2 in rat brain homogenate and blood plasma samples. In order to investigate the neurobehavioral abnormalities, rats were evaluated for muscular strength via the grip strength test (GST), locomotor deficits using open-field task (OFT), depressive behaviour with forced swim test (FST), and spatial learning in the Morris water maze (MWM) task. Chronic oral treatment with 4-HI at doses of 50 mg/kg and 100 mg/kg was given from days 22nd to 42nd of the experimental protocol to alleviate ALS-like symptoms in the MeHg model of rats. In addition to cellular, molecular, apoptotic, and neuroinflammatory assessments, neurotransmitter levels and oxidative stress indicators were examined in rat brain homogenates. The results of this study consistently show that 4-HI increases the level of neurotrophic growth factors such as IGF-1 and GLP-1 restores the altered neurochemical levels, and potentially prevents ALS-like gross pathological anomalies, including demyelination volume in the rat brain in a dose-dependent manner.

show abstract

Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Animal Model Of Methylmercury-induced Als-like Ratsmentioning

confidence: 99%

Section: Assessment Of Cellular and Molecular Markersmentioning

confidence: 99%

Section: Assessment Of Oxidative Stress Markersmentioning

confidence: 99%

See 3 more Smart Citations