Maylin Wong-Guerra, Yanay Montano-Peguero, Daniela Hernández-Enseñat, Jeney Ramírez-Sánchez, Abel Mondelo-Rodríguez, Alejandro Saúl Padrón-Yaquis, Enrique García-Alfonso, Luis Arturo Fonseca-Fonseca, Yanier Nuñez-Figueredo
{"title":"Mitochondrial protective properties exerted by JM-20 in a dementia model induced by intracerebroventricular administration of streptozotocin in mice.","authors":"Maylin Wong-Guerra, Yanay Montano-Peguero, Daniela Hernández-Enseñat, Jeney Ramírez-Sánchez, Abel Mondelo-Rodríguez, Alejandro Saúl Padrón-Yaquis, Enrique García-Alfonso, Luis Arturo Fonseca-Fonseca, Yanier Nuñez-Figueredo","doi":"10.1016/j.bbr.2024.115385","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction and brain insulin resistance have been related to Alzheimer's disease (AD) development. Streptozotocin (STZ) is commonly employed to disrupt glucose and insulin metabolism, even causing cognitive impairment in animal models. We aimed at studying the protective effect of JM-20 on STZ-induced memory impairment and brain mitochondrial dysfunction.</p><p><strong>Methods: </strong>Male C57Bl6 mice received 3 mg/kg STZ intracerebroventricularly and JM-20 (0.25 mg/kg or 4 mg/kg) was administered daily by gastric gavage. Episodic memory was evaluated through Y-maze, novel object recognition, and Morris water maze. Endogenous antioxidant systems (catalase and superoxide dismutase activities), total sulfhydryl groups, malondialdehyde levels were also studied and acetylcholinesterase (AChE) activity were assessed in the prefrontal cortex (PC) and hippocampus (HO).</p><p><strong>Results: </strong>demonstrated that STZ injection impaired recognition and spatial learning and memory and oxygen flow in all mitochondrial respiration states. Additionally, STZ increased AChE, superoxide dismutase, and catalase activity in the PC but not in HO tissue. A neuroprotective effect of JM-20 on STZ-induced memory decline, and mitochondrial dysfunction was observed, suggesting an important causal interaction. In addition, JM-20 was able to decreased AChE enzyme hyperactivity, rescued endogenous antioxidant systems, and prevented histologically observed neuronal damage CONCLUSION: Our results indicate that JM-20 protects against STZ-induced impairment in brain bioenergetic metabolism and memory, confirming its potential as a candidate for treating neurodegenerative disorders associated with mitochondrial dysfunction like AD.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115385"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1016/j.bbr.2024.115385","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Mitochondrial dysfunction and brain insulin resistance have been related to Alzheimer's disease (AD) development. Streptozotocin (STZ) is commonly employed to disrupt glucose and insulin metabolism, even causing cognitive impairment in animal models. We aimed at studying the protective effect of JM-20 on STZ-induced memory impairment and brain mitochondrial dysfunction.
Methods: Male C57Bl6 mice received 3 mg/kg STZ intracerebroventricularly and JM-20 (0.25 mg/kg or 4 mg/kg) was administered daily by gastric gavage. Episodic memory was evaluated through Y-maze, novel object recognition, and Morris water maze. Endogenous antioxidant systems (catalase and superoxide dismutase activities), total sulfhydryl groups, malondialdehyde levels were also studied and acetylcholinesterase (AChE) activity were assessed in the prefrontal cortex (PC) and hippocampus (HO).
Results: demonstrated that STZ injection impaired recognition and spatial learning and memory and oxygen flow in all mitochondrial respiration states. Additionally, STZ increased AChE, superoxide dismutase, and catalase activity in the PC but not in HO tissue. A neuroprotective effect of JM-20 on STZ-induced memory decline, and mitochondrial dysfunction was observed, suggesting an important causal interaction. In addition, JM-20 was able to decreased AChE enzyme hyperactivity, rescued endogenous antioxidant systems, and prevented histologically observed neuronal damage CONCLUSION: Our results indicate that JM-20 protects against STZ-induced impairment in brain bioenergetic metabolism and memory, confirming its potential as a candidate for treating neurodegenerative disorders associated with mitochondrial dysfunction like AD.
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.