Srivastava Nishi, Seth Kavita, Srivastava Nalini, Khanna Vinay K, Agrawal Ashok Kumar
Developmental Toxicology Division, Industrial Toxicology Research Centre, Post Box 80, M.G. Marg, Lucknow 226001, India.
Neurochem Res. 2008 Jul;33(7):1169-77. doi: 10.1007/s11064-007-9478-7. Epub 2007 Oct 23.
Neurogenesis occurs in dentate gyrus of adult hippocampus under the influence of various mitogenic factors. Growth factors besides instigating the proliferation of neuronal progenitor cells (NPCs) in dentate gyrus, also supports their differentiation to cholinergic neurons. In the present study, an attempt has been made to investigate the neurotrophic effect of bFGF in Kainic acid (KA) induced cognitive dysfunction in rats. Stereotaxic lesioning using (KA) was performed in hippocampal CA3 region of rat's brain. Four-weeks post lesioning rats were assessed for impairment in learning and memory using Y maze followed by bFGF infusion in dentate gyrus region. The recovery was evaluated after bFGF infusion using neurochemical, neurobehavioural and immunohistochemical approaches and compared with lesioned group. Significant impairment in learning and memory (P < 0.01) observed in lesioned animals, four weeks post lesioning exhibited significant restoration (P < 0.001) following bFGF infusion twice at one and four week post lesion. The bFGF infused animals exhibited recovery in hippocampus cholinergic (76%)/ dopaminergic (46%) receptor binding and enhanced Choline acetyltransferase (ChAT) immunoreactivity in CA3 region. The results suggest restorative potential of bFGF in cognitive dysfunctions, possibly due to mitogenic effect on dentate gyrus neurogenic area leading to generation and migration of newer cholinergic neurons.
在多种促有丝分裂因子的影响下,成体海马齿状回中会发生神经发生。生长因子除了能刺激齿状回中神经元祖细胞(NPCs)的增殖外,还能支持它们分化为胆碱能神经元。在本研究中,已尝试探究碱性成纤维细胞生长因子(bFGF)对 kainic 酸(KA)诱导的大鼠认知功能障碍的神经营养作用。在大鼠脑的海马 CA3 区使用(KA)进行立体定位损伤。损伤四周后,使用 Y 迷宫评估大鼠的学习和记忆损伤情况,随后在齿状回区域注入 bFGF。在注入 bFGF 后,使用神经化学、神经行为学和免疫组织化学方法评估恢复情况,并与损伤组进行比较。损伤动物在损伤四周后观察到学习和记忆有显著损伤(P < 0.01),在损伤后第一周和第四周两次注入 bFGF 后表现出显著恢复(P < 0.001)。注入 bFGF 的动物海马胆碱能(76%)/多巴胺能(46%)受体结合恢复,且 CA3 区胆碱乙酰转移酶(ChAT)免疫反应性增强。结果表明 bFGF 对认知功能障碍具有恢复潜力,这可能是由于其对齿状回神经发生区域的促有丝分裂作用,导致新的胆碱能神经元的产生和迁移。