Tikhonova Maria A, Ho Shih-Chun, Akopyan Anna A, Kolosova Nataliya G, Weng Jun-Cheng, Meng Wan-Yun, Lin Chih-Li, Amstislavskaya Tamara G, Ho Ying-Jui
Laboratory of Experimental Models of Neurodegenerative Processes, Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine" (SRIPhBM), Novosibirsk 630117, Russia; Academic Strategic Unit "Neuroscience in Translational Medicine", Novosibirsk State University, Novosibirsk 630090, Russia.
Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
Behav Brain Res. 2017 Jul 14;330:8-16. doi: 10.1016/j.bbr.2017.05.002. Epub 2017 May 6.
Rats of OXYS strain are characterized by genetically defined accelerated senescence. Ceftriaxone (CEF) exerts neuroprotective effects by decreasing the excitotoxicity and activation of antioxidant system. Here, we studied the effects of CEF (50 or 100mg/kg/day, i.p., 36 days) on cognitive and neuronal deficits in 5-month-old OXYS rats. Chronic CEF administration in a dose of 100mg/kg partially inhibited impairments of movement and restored the deficit in the novel object recognition in OXYS rats. Neuromorphologically, control OXYS rats exhibited a lowered neuronal density in the hippocampal CA1 area and there was a tendency to decrease in the substantia nigra pars compacta compared to Wistar controls. Both doses of CEF increased the density of pyramidal neurons in the CA1 area in OXYS rats. Control OXYS rats demonstrated a tendency to lower tyrosine hydroxylase (TH) immunoreactivity in the striatum compared with Wistar rats, while CEF treatment at a dose of 50mg/kg significantly augmented this parameter. In control OXYS rats, the levels of neurogenesis in the subgranular zone of the dentate gyrus of the hippocampus were significantly higher than in Wistar rats indicating compensatory processes that probably prevented the further induction of neurogenesis by CEF. Restoration of the recognition function and neuronal density in the CA1 area in OXYS rats after CEF treatment might be related to activation of the mechanisms that provide survival of newborn and mature neurons. The data suggested CEF as a promising pharmacological tool for the prevention of cognitive decline at accelerated aging.
OXYS品系大鼠的特点是具有基因定义的加速衰老。头孢曲松（CEF）通过降低兴奋性毒性和激活抗氧化系统发挥神经保护作用。在此，我们研究了CEF（50或100mg/kg/天，腹腔注射，共36天）对5月龄OXYS大鼠认知和神经元缺陷的影响。以100mg/kg的剂量长期给予CEF可部分抑制OXYS大鼠的运动障碍，并恢复其在新物体识别方面的缺陷。在神经形态学上，与Wistar对照大鼠相比，对照的OXYS大鼠海马CA1区神经元密度降低，黑质致密部有降低的趋势。两种剂量的CEF均增加了OXYS大鼠CA1区锥体神经元的密度。与Wistar大鼠相比，对照的OXYS大鼠纹状体中酪氨酸羟化酶（TH）免疫反应性有降低的趋势，而50mg/kg剂量的CEF治疗可显著提高该参数。在对照的OXYS大鼠中，海马齿状回颗粒下区的神经发生水平显著高于Wistar大鼠，这表明存在补偿过程，可能阻止了CEF对神经发生的进一步诱导。CEF治疗后OXYS大鼠CA1区识别功能和神经元密度的恢复可能与激活为新生和成熟神经元提供存活的机制有关。这些数据表明CEF是预防加速衰老过程中认知衰退的一种有前景的药理学工具。
