{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:45:51Z","timestamp":1791902751696,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Animal Ethics Committee (IAEC)","award":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"],"award-info":[{"award-number":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["ISFCP\/IAEC\/CPCSEA\/Meeting"],"award-info":[{"award-number":["ISFCP\/IAEC\/CPCSEA\/Meeting"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["N28\/2020\/Protocol No.455"],"award-info":[{"award-number":["N28\/2020\/Protocol No.455"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["RSP-2021\/335"],"award-info":[{"award-number":["RSP-2021\/335"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"],"award-info":[{"award-number":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["ISFCP\/IAEC\/CPCSEA\/Meeting"],"award-info":[{"award-number":["ISFCP\/IAEC\/CPCSEA\/Meeting"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["N28\/2020\/Protocol No.455"],"award-info":[{"award-number":["N28\/2020\/Protocol No.455"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP-2021\/335"],"award-info":[{"award-number":["RSP-2021\/335"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a severe adult motor neuron disease that causes progressive neuromuscular atrophy, muscle wasting, weakness, and depressive-like symptoms. Our previous research suggests that mercury levels are directly associated with ALS progression. MeHg+-induced ALS is characterised by oligodendrocyte destruction, myelin basic protein (MBP) depletion, and white matter degeneration, leading to demyelination and motor neuron death. The selection of MeHg+ as a potential neurotoxicant is based on our evidence that it has been connected to the development of ALS-like characteristics. It causes glutamate-mediated excitotoxicity, calcium-dependent neurotoxicity, and an ALS-like phenotype. Dysregulation of IGF-1\/GLP-1 signalling has been associated with ALS progression. The bioactive amino acid 4-hydroxyisoleucine (HI) from Trigonella foenum graecum acts as an insulin mimic in rodents and increases insulin sensitivity. This study examined the neuroprotective effects of 4-HI on MeHg+-treated adult Wistar rats with ALS-like symptoms, emphasising brain IGF1\/GLP-1 activation. Furthermore, we investigated the effect of 4-HI on MBP levels in rat brain homogenate, cerebrospinal fluid (CSF), blood plasma, and cell death indicators such as caspase-3, Bax, and Bcl-2. Rats were assessed for muscular strength, locomotor deficits, depressed behaviour, and spatial learning in the Morris water maze (MWM) to measure neurobehavioral abnormalities. Doses of 4-HI were given orally for 42 days in the MeHg+ rat model at 50 mg\/kg or 100 mg\/kg to ameliorate ALS-like neurological dysfunctions. Additionally, neurotransmitters and oxidative stress markers were examined in rat brain homogenates. Our findings suggest that 4-HI has neuroprotective benefits in reducing MeHg+-induced behavioural, neurochemical, and histopathological abnormalities in ALS-like rats exposed to methylmercury.<\/jats:p>","DOI":"10.3390\/molecules27123878","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T05:25:11Z","timestamp":1655443511000},"page":"3878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Activation of IGF-1\/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2699-5512","authenticated-orcid":false,"given":"Ambika","family":"Shandilya","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-835X","authenticated-orcid":false,"given":"Sidharth","family":"Mehan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranshul","family":"Sethi","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Acharan S.","family":"Narula","sequence":"additional","affiliation":[{"name":"Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metab","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-4287","authenticated-orcid":false,"given":"Abdullah F.","family":"Alasmari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1573407216999200723113054","article-title":"Neuroprotective potential of adenyl cyclase\/cAMP\/CREB and mitochondrial CoQ10 activator in amyotrophic lateral sclerosis rats","volume":"17","author":"Alam","year":"2021","journal-title":"Curr. 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