Heylmann Alexandra S Almeida, Canever Lara, Gress Katia, Gomes Sarah T, Fachim Isadora, Michels Carolina, Stopassoli Geórgia C, Mastella Gustavo A, Steckert Amanda V, Damiani Adriani P, de Andrade Vanessa M, Quevedo João, Zugno Alexandra I
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil.
Laboratório de Biologia Celular e Molecular, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Behav Brain Res. 2017 May 30;326:154-164. doi: 10.1016/j.bbr.2017.02.043. Epub 2017 Mar 8.
This study investigated the behavioral and biochemical parameters of DM1 as a risk factor in an animal model of schizophrenia (SZ). All groups: 1 Control (saline+saline); 2 Alloxan (alloxan+saline); 3 Ketamine (saline+ketamine); 4 (Alloxan+Ketamine) were fasted for a period of 18h before the subsequent induction of DM via a single intraperitoneal (i.p) injection of alloxan (150mg/kg). From the 4th to the 10th days, the animals were injected i.p with ketamine (25mg/kg) or saline, once a day, to induce a model of SZ and 30min after the last administration were subjected to behavioral testing. After, the animals were decapitated and the brain structures were removed. Ketamine induced hyperactivity and in the social interaction, ketamine, alloxan and the association of alloxan+ketamine increased the latency and decreased the number of contacts between animals. The animals from the ketamine, alloxan and alloxan+ketamine groups showed a prepulse startle reflex (PPI) deficit at the three intensities (65, 70 and 75dB). Ketamine was shown to be capable of increasing the activity of acetylcholinesterase (AChE) in the brain structures. Combination of alloxan+ketamine seems to have an exacerbated effect within the cholinergic system. For lipid peroxidation and protein carbonyls, alloxan+ketamine appear to have intensified lipid and protein damage in the three structures. Ketamine and the combination of ketamine+alloxan induced DNA damage in both frequency and damage index. This research found a relationship between DM1 and SZ.
本研究在精神分裂症（SZ）动物模型中，调查了作为风险因素的1型糖尿病（DM1）的行为和生化参数。所有组：1对照组（生理盐水+生理盐水）；2四氧嘧啶组（四氧嘧啶+生理盐水）；3氯胺酮组（生理盐水+氯胺酮）；4（四氧嘧啶+氯胺酮）组在通过单次腹腔注射四氧嘧啶（150mg/kg）诱导DM之前禁食18小时。从第4天到第10天，每天给动物腹腔注射氯胺酮（25mg/kg）或生理盐水，以诱导SZ模型，在最后一次给药后30分钟进行行为测试。之后，将动物断头并取出脑结构。氯胺酮诱导多动，在社交互动中，氯胺酮、四氧嘧啶以及四氧嘧啶+氯胺酮联合用药增加了潜伏期并减少了动物之间的接触次数。氯胺酮组、四氧嘧啶组和四氧嘧啶+氯胺酮组的动物在三种强度（65、70和75dB）下均表现出预脉冲惊吓反射（PPI）缺陷。氯胺酮被证明能够增加脑结构中乙酰胆碱酯酶（AChE）的活性。四氧嘧啶+氯胺酮联合用药似乎在胆碱能系统内具有加剧作用。对于脂质过氧化和蛋白质羰基化，四氧嘧啶+氯胺酮似乎在三种结构中加剧了脂质和蛋白质损伤。氯胺酮以及氯胺酮+四氧嘧啶联合用药在频率和损伤指数方面均诱导了DNA损伤。本研究发现了DM1与SZ之间的关系。
