Department of Psychology, Sociology, and Social Work, West Texas A&M University, Canyon, TX, USA.
Department of Psychology, Sociology, and Social Work, West Texas A&M University, Canyon, TX, USA.
Behav Brain Res. 2020 Jan 13;377:112257. doi: 10.1016/j.bbr.2019.112257. Epub 2019 Sep 22.
Mild cognitive impairment (MCI) is characterized by a reduction in cerebral blood flow. Permanent ligation of the common carotid arteries (2VO) in the rat mimics the chronic decrease in CBF that characterizes aMCI. The current study determined if melatonin (a pineal hormone with neuroprotective properties) can attenuate the neurobehavioral consequences of 2VO using middle-aged female rats. Two weeks following 2VO or sham surgery, rats were tested on various learning and memory tasks. 2VO resulted in hyperlocomotion on the open field. Melatonin attenuated this 2VO-induced hyperactivity. 2VO impaired visual memory however this was not attenuated by melatonin administration. Neither 2VO nor melatonin affected spatial memory performance on the MWM or spatial recognition task. Y-maze testing revealed 2VO rats exhibited a lower spontaneous alternation pattern and performed a greater number of alternate arm returns compared to 2VO rats treated with melatonin. 2VO resulted in a significant loss of CA1 hippocampal neurons which was attenuated with melatonin treatment. Chronic melatonin was found to attenuate the neuronal consequences of chronic cerebral hypoperfusion but only conferred partial behavioral protection in middle-aged female rats. Our results demonstrate that inclusion of older rodents is important in neuroprotection studies as neuroprotective agents may act differently in an aged brain.
轻度认知障碍（MCI）的特征是大脑血流减少。在大鼠中永久结扎颈总动脉（2VO）可模拟出与 aMCI 特征性的 CBF 慢性下降相类似的情况。本研究旨在确定褪黑素（一种具有神经保护特性的松果腺激素）是否可以减轻 2VO 对中年雌性大鼠神经行为后果的影响。在 2VO 或假手术 2 周后，对大鼠进行各种学习和记忆任务测试。2VO 导致旷场中的过度活跃。褪黑素减轻了这种 2VO 诱导的过度活跃。2VO 损害了视觉记忆，但褪黑素给药并未减轻这种损害。2VO 或褪黑素均未影响 MWM 或空间识别任务中的空间记忆表现。Y 迷宫测试显示，2VO 大鼠表现出较低的自发交替模式，并且与接受褪黑素治疗的 2VO 大鼠相比，进行了更多的交替臂返回。2VO 导致 CA1 海马神经元大量丧失，而褪黑素治疗可减轻这种损失。慢性褪黑素被发现可减轻慢性脑灌注不足的神经元后果，但仅在中年雌性大鼠中提供部分行为保护。我们的结果表明，在神经保护研究中纳入老年啮齿动物很重要，因为神经保护剂在老年大脑中的作用可能不同。
