中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1635-1642.doi: 10.4103/1673-5374.255982

• 原著:退行性病与再生 • 上一篇    下一篇

丘脑背内侧核损伤可逆转帕金森病大鼠大脑腹内侧前额叶皮质神经元的异常放电

  

  • 出版日期:2019-09-15 发布日期:2019-09-15
  • 基金资助:

    河南省科技重点研究项目(14B180007),洛阳市科技发展项目(1401087A-5)

Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats

Ling-Ling Fan , Bo Deng, Jun-Bao Yan, Zhi-Hong Hu, Ai-Hong Ren, Dong-Wei Yang   

  1. Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Ling-Ling Fan, PhD, emmafll@163.com.
  • Supported by:

    This work was supported by the Key Research Project of Science and Technology of Henan Province of China, No. 14B180007 (to LLF); and the Development Project of Science and Technology of Luoyang Municipality of China, No. 1401087A-5 (to LLF).

摘要:

腹内侧前额叶皮质的功能障碍既与情感障碍有关,又与帕金森病非运动特征有关。但背侧丘脑核在前额叶皮质功能中的确切作用仍不明确。为研究背侧丘脑核对6-羟基多巴胺诱导的中脑黑质致密部损伤后不同时期腹内侧前额叶皮质神经功能可能的影响,实验首先对大鼠大脑黑质致密部注射8 μg 6-羟多巴胺建立帕金森病模型,1或3周后于中脑背侧丘脑核注射0.3μg鹅膏蕈氨酸。于大脑黑质致密部损伤第3或5周时,以电生理仪检测大鼠大脑腹内侧前额叶皮质神经元的放电情况,以免疫组化染色检测大脑黑质致密部和腹侧被盖区中的多巴胺阳性神经元数量以及酪氨酸羟化酶的免疫阳性反应。结果显示,(1)6-羟多巴胺损伤后,大鼠大脑黑质致密部和腹侧被盖区中的多巴胺神经元以及酪氨酸羟化酶的免疫阳性反应减少;(2)与正常神经元相比,大脑黑质致密部损伤后第3和5周,大鼠大脑腹内侧前额叶皮质中锥体神经元放电频率增加,倾向于爆发性放电,放电间隔增加,中间神经元仅在放电频率下降,也倾向于爆发性放电,但放电间隔仅在3周时增加;(3)联合丘脑背内侧核损伤的大鼠在黑质致密部损伤后第3周时,腹内侧前额叶皮质锥体神经元以及中间神经元的放电频率、放电模式以及放电间隔可恢复至正常水平;(4)结果表明丘脑背内侧核损伤能参与调节大脑腹内侧前额叶皮质神经元的活动,同时丘脑背内侧核的功能变化可能与黑质致密部损伤后大脑腹内侧前额叶皮质神经元的异常放电活动有关。

orcid: 0000-0002-3866-3024 (Ling-Ling Fan)

关键词: 帕金森病, 丘脑背内侧核, 腹内侧前额叶皮质, 锥体神经元, 中间神经元, 放电, 神经再生

Abstract:

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease. How¬ever, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson’s disease was established by injecting 8 μg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxy¬lase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial pre¬frontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institu¬tional Animal Care and Use Committee of Xi’an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

Key words: nerve regeneration, Parkinson’s disease, mediodorsal thalamic nucleus, medial prefrontal cortex, pyramidal neurons, interneurons, discharge, neural regeneration