Femi-Akinlosotu Omowumi Moromoke, Olopade Funmilayo Eniola, Obiako Jane, Olopade James Olukayode, Shokunbi Matthew Temitayo
Developmental Neurobiology Laboratory, Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Neuroscience Unit, Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
Front Neurol. 2023 Feb 9;14:1116727. doi: 10.3389/fneur.2023.1116727. eCollection 2023.
Hydrocephalus is a neurological condition known to cause learning and memory disabilities due to its damaging effect on the hippocampal neurons, especially pyramidal neurons. Vanadium at low doses has been observed to improve learning and memory abilities in neurological disorders but it is uncertain whether such protection will be provided in hydrocephalus. We investigated the morphology of hippocampal pyramidal neurons and neurobehavior in vanadium-treated and control juvenile hydrocephalic mice.
Hydrocephalus was induced by intra-cisternal injection of sterile-kaolin into juvenile mice which were then allocated into 4 groups of 10 pups each, with one group serving as an untreated hydrocephalic control while others were treated with 0.15, 0.3 and 3 mg/kg i.p of vanadium compound respectively, starting 7 days post-induction for 28 days. Non-hydrocephalic sham controls ( = 10) were sham operated without any treatment. Mice were weighed before dosing and sacrifice. Y-maze, Morris Water Maze and Novel Object Recognition tests were carried out before the sacrifice, the brains harvested, and processed for Cresyl Violet and immunohistochemistry for neurons (NeuN) and astrocytes (GFAP). The pyramidal neurons of the CA1 and CA3 regions of the hippocampus were assessed qualitatively and quantitatively. Data were analyzed using GraphPad prism 8.
Escape latencies of vanadium-treated groups were significantly shorter (45.30 ± 26.30 s, 46.50 ± 26.35 s, 42.99 ± 18.44 s) than untreated group (62.06 ± 24.02 s) suggesting improvements in learning abilities. Time spent in the correct quadrant was significantly shorter in the untreated group (21.19 ± 4.15 s) compared to control (34.15 ± 9.44 s) and 3 mg/kg vanadium-treated group (34.35 ± 9.74 s). Recognition index and mean % alternation were lowest in untreated group ( = 0.0431, =0.0158) suggesting memory impairments, with insignificant improvements in vanadium-treated groups. NeuN immuno-stained CA1 revealed loss of apical dendrites of the pyramidal cells in untreated hydrocephalus group relative to control and a gradual reversal attempt in the vanadium-treated groups. Astrocytic activation (GFAP stain) in the untreated hydrocephalus group were attenuated in the vanadium-treated groups under the GFAP stain. Pyknotic index in CA1 pyramidal layer of untreated (18.82 ± 2.59) and 0.15mg/kg vanadium-treated groups (18.14 ± 5.92) were significantly higher than control (11.11 ± 0.93; = 0.0205, = 0.0373) while there was no significant difference in CA3 pyknotic index across all groups.
Our results suggest that vanadium has a dose-dependent protective effect on the pyramidal cells of the hippocampus and on memory and spatial learning functions in juvenile hydrocephalic mice.
脑积水是一种神经疾病，已知会因其对海马神经元尤其是锥体神经元的损害作用而导致学习和记忆障碍。已观察到低剂量钒可改善神经疾病中的学习和记忆能力，但在脑积水患者中是否能提供这种保护尚不确定。我们研究了钒处理组和对照组幼年脑积水小鼠海马锥体神经元的形态和神经行为。
通过向幼年小鼠脑池内注射无菌高岭土诱导脑积水，然后将其分为4组，每组10只幼崽，一组作为未处理的脑积水对照组，其他组分别腹腔注射0.15、0.3和3mg/kg的钒化合物，诱导后7天开始给药，持续28天。非脑积水假手术对照组（n = 10）进行假手术，不进行任何处理。给药前和处死前对小鼠称重。处死前进行Y迷宫、莫里斯水迷宫和新物体识别测试，然后收获大脑，进行甲酚紫染色以及神经元（NeuN）和星形胶质细胞（GFAP）的免疫组织化学检测。对海马CA1和CA3区域的锥体神经元进行定性和定量评估。使用GraphPad prism 8软件分析数据。
钒处理组的逃避潜伏期（45.30±26.30秒、46.50±26.35秒、42.99±18.44秒）明显短于未处理组（62.06±24.02秒），表明学习能力有所改善。与对照组（34.15±9.44秒）和3mg/kg钒处理组（34.35±9.74秒）相比，未处理组在正确象限花费的时间明显更短（21.19±4.15秒）。未处理组的识别指数和平均交替百分比最低（分别为0.0431、0.0158），表明存在记忆障碍，钒处理组虽有改善但不显著。NeuN免疫染色显示，未处理脑积水组海马CA1区锥体细胞的顶树突相对于对照组有所丢失，而钒处理组有逐渐恢复的趋势。在GFAP染色下，未处理脑积水组的星形胶质细胞激活在钒处理组中有所减弱。未处理组（18.82±2.59）和0.15mg/kg钒处理组（18.14±5.92）CA1锥体层的固缩指数显著高于对照组（11.11±0.93；p = 0.0205，p = 0.0373），而所有组的CA3固缩指数无显著差异。
我们的结果表明，钒对幼年脑积水小鼠海马的锥体细胞以及记忆和空间学习功能具有剂量依赖性保护作用。
