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脑室内注射D-半乳糖会损害大鼠的记忆,并改变其乙酰胆碱酯酶的活性和表达。

Intracerebroventricular D-galactose administration impairs memory and alters activity and expression of acetylcholinesterase in the rat.

作者信息

Rodrigues André Felipe, Biasibetti Helena, Zanotto Bruna Stela, Sanches Eduardo Farias, Pierozan Paula, Schmitz Felipe, Parisi Mariana Migliorini, Barbé-Tuana Florencia, Netto Carlos Alexandre, Wyse Angela T S

机构信息

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.

出版信息

Int J Dev Neurosci. 2016 May;50:1-6. doi: 10.1016/j.ijdevneu.2016.01.007. Epub 2016 Mar 4.

DOI:10.1016/j.ijdevneu.2016.01.007
PMID:26948151
Abstract

Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia.

摘要

半乳糖在组织中的蓄积是经典型半乳糖血症的一个标志。认知缺陷是这种疾病的一种症状,目前对此了解甚少。本研究的目的是探讨脑室内注射半乳糖对成年大鼠记忆(抑制性回避和新物体识别任务)的影响。我们还研究了半乳糖对海马体和大脑皮层中乙酰胆碱酯酶(AChE)活性、免疫含量和基因表达的影响。Wistar大鼠接受单次注射半乳糖(4mM)或生理盐水(对照组)。对于行为参数,在测试前1小时或24小时注射半乳糖。为了进行生化评估,在注射半乳糖或生理盐水后1小时、3小时或24小时将动物断头;解剖海马体和大脑皮层。结果表明,半乳糖会损害大鼠厌恶记忆(抑制性回避任务)和识别记忆(新物体识别任务)中的记忆形成过程。海马体中AChE的活性增加,而该酶的基因表达降低,但大脑皮层中没有这种情况。这些发现表明,AChE的这些变化可能至少部分导致了半乳糖引起的记忆损害。综上所述,我们的结果有助于理解经典型半乳糖血症的病因病理。

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