Matheus Gabriel de Freitas Nascimento, Josimar Macedo de Castro, Liciane Fernandes Medeiros, Khetrüin Jordana Fiuza, Thais Collioni de Oliveira, Iala Thais de Sousa Morais, Tenille Dal Bosco, Wolnei Caumo, Dirson J. Stein, Iraci L. S. Torres
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引用次数: 0
摘要
本研究考察了早期环境富集(EE)对反复暴露于吗啡的新生大鼠的神经运动、痛觉、认知、行为和神经化学参数的中长期影响。该研究采用了 90 只 Wistar 大鼠:其中包括 10 只成年无产仔雌性大鼠和 80 只雄性幼鼠。幼鼠被分成标准和 EE 两种饲养方式。之后,每窝大鼠的一半接受生理盐水(S)或吗啡(M)注射,共分为四组:SC+S组、EE+S组、SC+M组和EE+M组。从PND1到PND21注射EE,而从PND8到PND14每天注射吗啡或生理盐水(5 μg/s.c.)。各组的神经运动发育情况相似。在OF试验中,吗啡减少了大鼠的外侧越线和总越线次数,而EE则增加了大鼠的内侧越线和后退次数。成年大鼠的外交叉和总交叉次数以及梳理次数减少,而饲养次数增加。EE 增加了保护性和非保护性头部浸入的次数。成年大鼠受保护的头部浸入次数增加。成年大鼠的识别指数较低,暴露于 EE 时,焦虑指数和镇痛指数较低。EE 增加了脑干和海马 BDNF 水平。成年大鼠的下丘脑、脊髓和脑干 BDNF 水平升高,脊髓水平升高,下丘脑 TNF-α 水平降低。这项研究表明,早期 EE 可提高大鼠脑干和海马中的 BDNF 水平,并以状态依赖(吗啡和年龄)的方式改变大鼠的行为(如痛觉、探索和焦虑)。
Long-lasting behavioral and neurochemical effects of early-life environmental enrichment in rats submitted to neonatal morphine administration
The present study examined the medium- and long-term effects of early environmental enrichment (EE) on neuromotor, nociceptive, cognitive, behavioral, and neurochemical parameters in newborn rats repeatedly exposed to morphine. The study employed 90 Wistar rats: 10 adult nulliparous females and 80 male pups. Litter was split into standard and EE housing. Following, half of each litter received saline (S) or morphine (M) injections, resulting in four groups: SC + S, EE + S, SC + M, and EE + M. EE was applied from PND1 to PND21, while morphine or saline was given daily (5 μg/s.c.) from PND8 to PND14. Neuromotor development was similar between groups. In the OF test, morphine reduced outer and total crossings, whereas EE increased inner crossings and rearings. Adult rats showed a decrease in outer and total crossings and grooming and an increase in rearing. EE increased the number of protected and unprotected head dipping. Adult rats showed an increase in protected head dipping. Adult rats showed a lower recognition index, and, when exposed to EE, a lower anxiety index and analgesia. EE increased brainstem and hippocampal BDNF levels. Adult rats had increased hypothalamus, spinal cord, and brainstem BDNF levels, an increase in the spinal cord, and decreased hypothalamus TNF-α levels. This study demonstrated that early-life EE raises BDNF levels in the brainstem and hippocampus of rats and modifies their behaviors (such as nociception, exploration, and anxiety) in a state-dependent manner (morphine and age).
期刊介绍:
International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.