{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:31:07Z","timestamp":1783675867735,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. Methods: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg\u00b7kg\u22121, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg\/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. Results: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. Conclusion: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms21144901","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7918-7992","authenticated-orcid":false,"given":"Minsook","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Biomedicine &amp; Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-9538","authenticated-orcid":false,"given":"Jin Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine &amp; Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8014-9782","authenticated-orcid":false,"given":"Insop","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"The Neuroprotective Effect of Gugijihwang-Tang on Trimethyltin-Induced Memory Dysfunction in the Rat","volume":"2013","author":"Jung","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/6981595","article-title":"Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid","volume":"2016","author":"Kang","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.ntt.2011.09.003","article-title":"Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish","volume":"33","author":"Chen","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejphar.2018.10.019","article-title":"The neuroprotective effect of lithium chloride on cognitive impairment through glycogen synthase kinase-3beta inhibition in intracerebral hemorrhage rats","volume":"840","author":"Liu","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1471-4159.2012.07770.x","article-title":"The neuroprotective and neurogenic effects of neuropeptide Y administration in an animal model of hippocampal neurodegeneration and temporal lobe epilepsy induced by trimethyltin","volume":"122","author":"Corvino","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_6","first-page":"367","article-title":"Trimethyltin reduces recurrent inhibition in rats","volume":"6","author":"Dyer","year":"1984","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_7","first-page":"145","article-title":"Changes in neurobiological parameters in the hippocampus after exposure to trimethyltin","volume":"6","author":"Naalsund","year":"1985","journal-title":"NeuroToxicology"},{"key":"ref_8","first-page":"357","article-title":"Selective neurochemical and histological lesions in rat hippocampus following chronic trimethyltin exposure","volume":"5","author":"Valdes","year":"1983","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/15287398509530770","article-title":"Early effects of trimethyltin on the dentate gyrus basket cells: A morphological study","volume":"16","author":"Chang","year":"1985","journal-title":"J. Toxicol. Environ. Heal. Part A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1023\/A:1022482106152","article-title":"GM1 ganglioside potentiates trimethyltin-induced expression of interleukin-1 beta and the nerve growth factor in reactive astrocytes in the rat hippocampus: An immunocytochemical study","volume":"23","author":"Zaremba","year":"1998","journal-title":"Neurochem. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0736-5748(99)00111-2","article-title":"Long-term microglial and astroglial activation in the hippocampus of trimethyltin-intoxicated rat: Stimulation of NGF and TrkA immunoreactivities in astroglia but not in microglia","volume":"18","author":"Koczyk","year":"2000","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuro.2005.06.005","article-title":"Trimethyltin-induced alterations in behavior are linked to changes in PSA-NCAM expression","volume":"27","author":"Halladay","year":"2006","journal-title":"NeuroToxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1248\/bpb.b16-00045","article-title":"Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice","volume":"39","author":"Kim","year":"2016","journal-title":"Boil. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3389\/fendo.2017.00366","article-title":"Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review","volume":"8","author":"Lima","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0031-9384(94)90387-5","article-title":"Effects of trimethyltin on acquisition and reversal of a light-dark discrimination by rats","volume":"55","author":"Woodruff","year":"1994","journal-title":"Physiol. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0887-2333(92)90023-K","article-title":"Effects of organotins on the cholinergic system in the chicken brain in vitro","volume":"6","author":"Kobayashi","year":"1992","journal-title":"Toxicol. Vitr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/jnnp.66.2.137","article-title":"The cholinergic hypothesis of Alzheimer\u2019s disease: A review of progress","volume":"66","author":"Francis","year":"1999","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1472-8206.2008.00578.x","article-title":"Current and future therapy in Alzheimer\u2019s disease","volume":"22","year":"2008","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.pnpbp.2010.05.031","article-title":"Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats","volume":"34","author":"Lee","year":"2010","journal-title":"Prog. Neuro-Psychopharm. Boil. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1749-6632.1991.tb00227.x","article-title":"Use of Phosphatidylserine in Alzheimer\u2019s Disease","volume":"640","author":"Amaducci","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3233\/JAD-2009-1060","article-title":"Bovine Spongiform Encephalopathy and Aquaculture","volume":"17","author":"Friedland","year":"2008","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3164\/jcbn.10-62","article-title":"Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints","volume":"47","author":"Sakai","year":"2010","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/1028415X.2001.11747356","article-title":"The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment","volume":"4","author":"Jorissen","year":"2001","journal-title":"Nutr. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0072-9752(07)01213-4","article-title":"Economical Aspects of Dementia","volume":"89","author":"Wimo","year":"2008","journal-title":"Hendbook Clin. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00377794","article-title":"Trimethyltin poisoning report of two cases","volume":"41","author":"Fortemps","year":"1978","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_26","first-page":"659","article-title":"Physiological methods for assessment of Trimethyltin exposure","volume":"4","author":"Dyer","year":"1982","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_27","first-page":"59","article-title":"The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat","volume":"97","author":"Brown","year":"1979","journal-title":"Am. J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0013-9351(83)90226-8","article-title":"Neuropathology of trimethyltin intoxication. III. Changes in the brain stem neurons","volume":"30","author":"Chang","year":"1983","journal-title":"Environ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0306-4522(88)90150-9","article-title":"Trimethyltin-induced neuronal damage in the rat brain: Comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neuronotypic and gliotypic proteins","volume":"26","author":"Balaban","year":"1988","journal-title":"Neuroscience"},{"key":"ref_30","first-page":"443","article-title":"A time-course study of trimethyltin induced neuropathology in rats","volume":"5","author":"Chang","year":"1983","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_31","first-page":"673","article-title":"Trimethyltin induced pathology in sensory neurons","volume":"5","author":"Chang","year":"1983","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_32","first-page":"337","article-title":"Species and strain comparison of acute neurotoxic effects of trimethyltin in mice and rats","volume":"5","author":"Chang","year":"1983","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_33","first-page":"43","article-title":"Septotemporal gradients of trimethyltin-induced hippocampal lesions","volume":"7","author":"Chang","year":"1985","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0006-8993(97)01358-9","article-title":"Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures","volume":"783","author":"Noraberg","year":"1998","journal-title":"Brain Res."},{"key":"ref_35","first-page":"169","article-title":"Imparied maze performance in the rat caused by trimethyltin treatment: Problem-solving deficits and perseveration","volume":"4","author":"Swartzwelder","year":"1982","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_36","first-page":"201","article-title":"Time-course of trimethyltin effects on the monoaminergic systems of the rat brain","volume":"16","author":"Andersson","year":"1995","journal-title":"NeuroToxicology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"237","DOI":"10.55782\/ane-1996-1126","article-title":"Trimethyltin-induced plastic neuronal changes in rat hippocampus are accompanied by astrocytic trophic activity","volume":"56","author":"Koczyk","year":"1996","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_38","first-page":"20","article-title":"(Effect of Tremella fuciformis Berk on acute radiation sickness in dogs (author\u2019s transl))","volume":"4","author":"Zhao","year":"1982","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"ref_39","first-page":"163","article-title":"Trimethyltin impairs retention of a passive avoidance task","volume":"4","author":"Walsh","year":"1982","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.pa.21.040181.001543","article-title":"The Pharmacology of Memory: A Neurobiological Perspective","volume":"21","author":"Squire","year":"1981","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0091-6773(75)90793-2","article-title":"Activity changes related to the location of lesions in the hippocampus","volume":"13","author":"Lanier","year":"1975","journal-title":"Behav. Boil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0736-5748(03)00039-X","article-title":"Restorative potential of cholinergic rich transplants in cholchicine induced lesioned rats: A comparative study of single and multiple micro-transplantation approach","volume":"21","author":"Agrawal","year":"2003","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0091-3057(96)00431-5","article-title":"Acetylcholine, Aging, and Alzheimer\u2019s Disease","volume":"56","author":"Muir","year":"1997","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(98)00047-1","article-title":"Effect of entorhinal cortex lesion on hippocampal cholinergic system in rat in operant learning task as studied by in vivo brain microdialysis","volume":"157","author":"Shinjo","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-3-7091-6139-5_17","article-title":"Long-term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer\u2019 disease","volume":"62","author":"Giacobini","year":"2002","journal-title":"J. Neural. Transm. Suppl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/0006-8993(96)00427-1","article-title":"Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat\u2019s passive avoidance response: A tetrodotoxin functional inactivation study","volume":"730","author":"Lorenzini","year":"1996","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4103\/0257-7941.107361","article-title":"Estimation of total alkaloid in Chitrakadivati by UV-Spectrophotometer","volume":"31","author":"Ajanal","year":"2012","journal-title":"Anc. Sci. Life"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2967\/jnumed.108.056374","article-title":"Performance evaluation of the inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards","volume":"50","author":"Bao","year":"2009","journal-title":"J. Nucl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:17Z","timestamp":1760176217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,11]]},"references-count":48,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21144901"],"URL":"https:\/\/doi.org\/10.3390\/ijms21144901","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,11]]}}}