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在出生后发育期间耗竭 5-羟色胺会导致大鼠的行为和认知改变,并降低大脑中的 BDNF 水平。

Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats.

机构信息

Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

出版信息

Int J Dev Neurosci. 2021 Apr;81(2):179-190. doi: 10.1002/jdn.10087. Epub 2021 Jan 20.

Abstract

A survey of the literature indicates that the developmental disruptions in serotonin (5-HT) levels can influence the brain development and the function. To the best of our knowledge, so far, there are a few studies about the effects of developmental period 5-HT depletion on cognition and behavior of adult male and female rats. Therefore, in the present study, we examined the effects of postnatal days (PND 10-20) administration of para-chlorophenylalanine (PCPA, 100 mg/kg, s.c) a 5-HT synthesis inhibitor, on anxiety-related behaviors, pain sensitivity, short-term recognition memory, and hippocampal and prefrontal cortex (PFC) brain-derived neurotrophic factor (BDNF) mRNA expression in adult male and female rats. Novel object recognition memory (NORM) and behavioral parameters (anxiety-like behaviors and pain sensitivity) were evaluated in early adulthood and after that, the hippocampi and PFC of the rat's brain were removed for the determination of BDNF mRNA expression. Our results indicated that the postnatal period administration of PCPA impaired short-term NORM. The postnatal developmental period treatment with PCPA also increased anxiety-like behaviors in the open field and elevated plus maze (EPM) tests. Postnatal PCPA treatment increased pain sensitivity in the hot plate test in both male and female rats, especially in female animals. In addition, postnatal days serotonin depletion decreased BDNF level in the hippocampus and PFC of both male and female rats. These findings demonstrate that serotonin plays the main role in neurodevelopment, cognitive functions, and behavior. Therefore, serotonergic system dysregulation during the developmental periods may have more adverse influences on the brain development of rats.

摘要

文献调查表明,血清素(5-HT)水平的发育紊乱会影响大脑的发育和功能。据我们所知,目前关于发育时期 5-HT 耗竭对成年雄性和雌性大鼠认知和行为的影响的研究很少。因此,在本研究中,我们研究了在产后第 10-20 天(PND)给予对氯苯丙氨酸(PCPA,100mg/kg,皮下注射),一种 5-HT 合成抑制剂,对成年雄性和雌性大鼠焦虑相关行为、疼痛敏感性、短期识别记忆以及海马和前额皮质(PFC)脑源性神经营养因子(BDNF)mRNA 表达的影响。在成年早期评估新物体识别记忆(NORM)和行为参数(焦虑样行为和疼痛敏感性),然后取出大鼠大脑的海马体和 PFC 以测定 BDNF mRNA 表达。我们的结果表明,产后给予 PCPA 会损害短期 NORM。产后发育期间用 PCPA 处理还会增加旷场和高架十字迷宫(EPM)测试中的焦虑样行为。产后 PCPA 处理会增加雄性和雌性大鼠在热板测试中的疼痛敏感性,尤其是雌性动物。此外,产后血清素耗竭会降低雄性和雌性大鼠海马体和 PFC 中的 BDNF 水平。这些发现表明,血清素在神经发育、认知功能和行为中起主要作用。因此,发育期间 5-羟色胺能系统的失调可能对大鼠的大脑发育产生更不利的影响。

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