Olatunji Sunday Yinka, Ogunnaike Philip Olubunmi, Abijo Ayodeji Zabdiel, Owolabi Joshua Oladele, Adelodun Stephen Taiye, Adeoye Ayodele, Fasesan Oluwatoyin Adetutu, Olanrewaju John Afees, Adegbite Ademola Kayode
{"title":"经口暴露于大麻乙醇提取物引起Wistar大鼠前额皮质神经元变性和星形胶质细胞增生。","authors":"Olatunji Sunday Yinka, Ogunnaike Philip Olubunmi, Abijo Ayodeji Zabdiel, Owolabi Joshua Oladele, Adelodun Stephen Taiye, Adeoye Ayodele, Fasesan Oluwatoyin Adetutu, Olanrewaju John Afees, Adegbite Ademola Kayode","doi":"10.1177/09727531221120988","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite widespread concerns about its possible side effects, notably on the prefrontal cortex (PFC), which mediates cognitive processes, the use of <i>Cannabis sativa</i> as a medicinal and recreational drug is expanding exponentially. This study evaluated possible behavioral alterations, neurotransmitter levels, histological, and immunohistochemical changes in the PFC of Wistar rats exposed to <i>Cannabis sativa</i>.</p><p><strong>Purpose: </strong>To evaluate the effect of graded doses of <i>Cannabis sativa</i> on the PFC using behavioural, histological, and immunohistochemical approaches.</p><p><strong>Methods: </strong>Twenty-eight juvenile male Wistar rats weighing between 70 g and 100 g were procured and assigned into groups A-D (<i>n</i> = 7 each). Group A served as control which received distilled water only as a placebo; rats in groups B, C, and D which were the treatment groups were orally exposed to graded doses of <i>Cannabis sativa</i> (10 mg/kg, 50 mg/kg, and 100 mg/kg, respectively). Rats in all experimental groups were exposed to <i>Cannabis sativa</i> for 21 days, followed by behavioral tests using the open field test for locomotor, anxiety, and exploratory activities, while the Y-maze test was for spatial memory assessment. Rats for biochemical analysis were cervically dislocated and rats for tissue processing were intracardially perfused following neurobehavioral tests. Sequel to sacrifice, brain tissues were excised and prefrontal cortices were obtained for the neurotransmitter (glutamate, acetylcholine, and dopamine) and enzymatic assay (Cytochrome C oxidase (CcO) and Glucose 6- Phosphate Dehydrogenase-G-6-PDH). Brain tissues were fixed in 10% Neutral Buffered Formalin (NBF) for histological demonstration of the PFC cytoarchitecture using H&E and glial fibrillary acidic protein (GFAP) for astrocyte evaluation.</p><p><strong>Results: </strong>Glutamate and dopamine levels were significantly increased (<i>F</i> = 24.44, <i>P</i> = .0132) in groups D, and B, C, and D, respectively, compared to control; likewise, the activities of CcO and G-6-PDH were also significantly elevated (<i>F</i> = 96.28, <i>P</i> = .0001) (<i>F</i> = 167.5, <i>P</i> = .0001) in groups C and D compared to the control. <i>Cannabis sativa</i> impaired locomotor activity and spatial memory in B and D and D, respectively. All <i>Cannabis sativa</i> exposed groups demonstrated evidence of neurodegeneration in the exposed groups; GFAP immunoexpression was evident in all groups with a marked increase in group D.</p><p><strong>Conclusion: </strong><i>Cannabis sativa</i> altered neurotransmitter levels, energy metabolism, locomotor, and exploratory activity, and spatial working memory, with neuronal degeneration as well as reactive astrogliosis in the PFC.</p>","PeriodicalId":7921,"journal":{"name":"Annals of Neurosciences","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/e2/10.1177_09727531221120988.PMC10496793.pdf","citationCount":"0","resultStr":"{\"title\":\"Peroral Exposure to <i>Cannabis Sativa</i> Ethanol Extract Caused Neuronal Degeneration and Astrogliosis in Wistar Rats' Prefrontal Cortex.\",\"authors\":\"Olatunji Sunday Yinka, Ogunnaike Philip Olubunmi, Abijo Ayodeji Zabdiel, Owolabi Joshua Oladele, Adelodun Stephen Taiye, Adeoye Ayodele, Fasesan Oluwatoyin Adetutu, Olanrewaju John Afees, Adegbite Ademola Kayode\",\"doi\":\"10.1177/09727531221120988\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Despite widespread concerns about its possible side effects, notably on the prefrontal cortex (PFC), which mediates cognitive processes, the use of <i>Cannabis sativa</i> as a medicinal and recreational drug is expanding exponentially. This study evaluated possible behavioral alterations, neurotransmitter levels, histological, and immunohistochemical changes in the PFC of Wistar rats exposed to <i>Cannabis sativa</i>.</p><p><strong>Purpose: </strong>To evaluate the effect of graded doses of <i>Cannabis sativa</i> on the PFC using behavioural, histological, and immunohistochemical approaches.</p><p><strong>Methods: </strong>Twenty-eight juvenile male Wistar rats weighing between 70 g and 100 g were procured and assigned into groups A-D (<i>n</i> = 7 each). Group A served as control which received distilled water only as a placebo; rats in groups B, C, and D which were the treatment groups were orally exposed to graded doses of <i>Cannabis sativa</i> (10 mg/kg, 50 mg/kg, and 100 mg/kg, respectively). Rats in all experimental groups were exposed to <i>Cannabis sativa</i> for 21 days, followed by behavioral tests using the open field test for locomotor, anxiety, and exploratory activities, while the Y-maze test was for spatial memory assessment. Rats for biochemical analysis were cervically dislocated and rats for tissue processing were intracardially perfused following neurobehavioral tests. Sequel to sacrifice, brain tissues were excised and prefrontal cortices were obtained for the neurotransmitter (glutamate, acetylcholine, and dopamine) and enzymatic assay (Cytochrome C oxidase (CcO) and Glucose 6- Phosphate Dehydrogenase-G-6-PDH). Brain tissues were fixed in 10% Neutral Buffered Formalin (NBF) for histological demonstration of the PFC cytoarchitecture using H&E and glial fibrillary acidic protein (GFAP) for astrocyte evaluation.</p><p><strong>Results: </strong>Glutamate and dopamine levels were significantly increased (<i>F</i> = 24.44, <i>P</i> = .0132) in groups D, and B, C, and D, respectively, compared to control; likewise, the activities of CcO and G-6-PDH were also significantly elevated (<i>F</i> = 96.28, <i>P</i> = .0001) (<i>F</i> = 167.5, <i>P</i> = .0001) in groups C and D compared to the control. <i>Cannabis sativa</i> impaired locomotor activity and spatial memory in B and D and D, respectively. All <i>Cannabis sativa</i> exposed groups demonstrated evidence of neurodegeneration in the exposed groups; GFAP immunoexpression was evident in all groups with a marked increase in group D.</p><p><strong>Conclusion: </strong><i>Cannabis sativa</i> altered neurotransmitter levels, energy metabolism, locomotor, and exploratory activity, and spatial working memory, with neuronal degeneration as well as reactive astrogliosis in the PFC.</p>\",\"PeriodicalId\":7921,\"journal\":{\"name\":\"Annals of Neurosciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/e2/10.1177_09727531221120988.PMC10496793.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurosciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/09727531221120988\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurosciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/09727531221120988","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景:尽管人们普遍担心大麻可能产生的副作用,尤其是对调节认知过程的前额叶皮质(PFC)的副作用,但大麻作为一种药用和娱乐性药物的使用正在呈指数级增长。本研究评估暴露于大麻的Wistar大鼠PFC可能的行为改变、神经递质水平、组织学和免疫组织化学变化。目的:利用行为学、组织学和免疫组织化学方法评估分级剂量大麻对PFC的影响。方法:取体重70 ~ 100 g的雄性Wistar幼年大鼠28只,随机分为A-D组,每组7只。A组作为对照组,只接受蒸馏水作为安慰剂;B组、C组、D组为治疗组,分别以10 mg/kg、50 mg/kg、100 mg/kg的分级剂量口服大麻。所有实验组大鼠暴露于大麻21天,随后进行运动、焦虑和探索性活动行为测试,y形迷宫测试空间记忆评估。生化分析用大鼠颈脱位,组织处理用大鼠心内灌注神经行为试验。牺牲后,切除脑组织,获得前额皮质用于神经递质(谷氨酸、乙酰胆碱和多巴胺)和酶分析(细胞色素C氧化酶(CcO)和葡萄糖6-磷酸脱氢酶g -6- pdh)。脑组织固定在10%中性缓冲福尔马林(NBF)中,用H&E和胶质纤维酸性蛋白(GFAP)对PFC细胞结构进行组织学展示,对星形胶质细胞进行评估。结果:与对照组相比,D组、B组、C组、D组谷氨酸、多巴胺水平均显著升高(F = 24.44, P = 0.0132);C组和D组CcO和G-6-PDH活性也显著高于对照组(F = 96.28, P = 0.0001) (F = 167.5, P = 0.0001)。大麻分别损害了B、D和D的运动活动和空间记忆。所有大麻暴露组均表现出神经变性的证据;结论:大麻改变了PFC的神经递质水平、能量代谢、运动、探索活动和空间工作记忆,并伴有神经元变性和反应性星形胶质变。
Peroral Exposure to Cannabis Sativa Ethanol Extract Caused Neuronal Degeneration and Astrogliosis in Wistar Rats' Prefrontal Cortex.
Background: Despite widespread concerns about its possible side effects, notably on the prefrontal cortex (PFC), which mediates cognitive processes, the use of Cannabis sativa as a medicinal and recreational drug is expanding exponentially. This study evaluated possible behavioral alterations, neurotransmitter levels, histological, and immunohistochemical changes in the PFC of Wistar rats exposed to Cannabis sativa.
Purpose: To evaluate the effect of graded doses of Cannabis sativa on the PFC using behavioural, histological, and immunohistochemical approaches.
Methods: Twenty-eight juvenile male Wistar rats weighing between 70 g and 100 g were procured and assigned into groups A-D (n = 7 each). Group A served as control which received distilled water only as a placebo; rats in groups B, C, and D which were the treatment groups were orally exposed to graded doses of Cannabis sativa (10 mg/kg, 50 mg/kg, and 100 mg/kg, respectively). Rats in all experimental groups were exposed to Cannabis sativa for 21 days, followed by behavioral tests using the open field test for locomotor, anxiety, and exploratory activities, while the Y-maze test was for spatial memory assessment. Rats for biochemical analysis were cervically dislocated and rats for tissue processing were intracardially perfused following neurobehavioral tests. Sequel to sacrifice, brain tissues were excised and prefrontal cortices were obtained for the neurotransmitter (glutamate, acetylcholine, and dopamine) and enzymatic assay (Cytochrome C oxidase (CcO) and Glucose 6- Phosphate Dehydrogenase-G-6-PDH). Brain tissues were fixed in 10% Neutral Buffered Formalin (NBF) for histological demonstration of the PFC cytoarchitecture using H&E and glial fibrillary acidic protein (GFAP) for astrocyte evaluation.
Results: Glutamate and dopamine levels were significantly increased (F = 24.44, P = .0132) in groups D, and B, C, and D, respectively, compared to control; likewise, the activities of CcO and G-6-PDH were also significantly elevated (F = 96.28, P = .0001) (F = 167.5, P = .0001) in groups C and D compared to the control. Cannabis sativa impaired locomotor activity and spatial memory in B and D and D, respectively. All Cannabis sativa exposed groups demonstrated evidence of neurodegeneration in the exposed groups; GFAP immunoexpression was evident in all groups with a marked increase in group D.
Conclusion: Cannabis sativa altered neurotransmitter levels, energy metabolism, locomotor, and exploratory activity, and spatial working memory, with neuronal degeneration as well as reactive astrogliosis in the PFC.