Perdikaris Panagiotis, Prouska Paulina, Dermon Catherine R
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Patras, Greece.
Front Behav Neurosci. 2023 Oct 16;17:1244075. doi: 10.3389/fnbeh.2023.1244075. eCollection 2023.
Accumulating evidence highlights the key role of adult neurogenesis events in environmental challenges, cognitive functions and mood regulation. Abnormal hippocampal neurogenesis has been implicated in anxiety-like behaviors and social impairments, but the possible mechanisms remain elusive.
The present study questioned the contribution of altered excitation/inhibition as well as excessive neuroinflammation in regulating the neurogenic processes within the Social Decision-Making (SDM) network, using an adult zebrafish model displaying NMDA receptor hypofunction after sub-chronic MK-801 administration. For this, the alterations in cell proliferation and newborn cell densities were evaluated using quantitative 5-Bromo-2'-Deoxyuridine (BrdU) methodology.
In short-term survival experiments. MK-801-treated zebrafish displayed decreased cell proliferation pattern within distinct neurogenic zones of telencephalic and preoptic SDM nodes, in parallel to the social withdrawal and anxiety-like comorbidity. BrdU+ cells co-expressed the pro-inflammatory marker IL-1β solely in MK-801-treated zebrafish, indicating a role of inflammation. Following the cessation of drug treatment, significant increases in the BrdU+ cell densities were accompanied by the normalization of the social and anxiety-like phenotype. Importantly, most labeled cells in neurogenic zones showed a radial glial phenotype while a population of newborn cells expressed the early neuronal marker TOAD or mGLuR5, the latter suggesting the possible involvement of metabotropic glutamate receptor 5 in neurogenic events.
Overall, our results indicate the role of radial glial cell proliferation in the overlapping pathologies of anxiety and social disorders, observed in many neuropsychiatric disorders and possibly represent potential novel targets for amelioration of these symptoms.
越来越多的证据表明，成体神经发生事件在应对环境挑战、认知功能和情绪调节中起着关键作用。海马神经发生异常与焦虑样行为和社交障碍有关，但其潜在机制仍不清楚。
本研究利用成年斑马鱼模型，在亚慢性给予MK-801后表现出NMDA受体功能减退，探讨兴奋性/抑制性改变以及过度神经炎症在调节社会决策（SDM）网络内神经发生过程中的作用。为此，使用定量5-溴-2'-脱氧尿苷（BrdU）方法评估细胞增殖和新生细胞密度的变化。
在短期存活实验中。MK-801处理的斑马鱼在端脑和视前SDM节点的不同神经发生区域内细胞增殖模式降低，同时伴有社交退缩和焦虑样共病。BrdU+细胞仅在MK-801处理的斑马鱼中共表达促炎标志物IL-1β，表明炎症起作用。药物治疗停止后，BrdU+细胞密度显著增加，同时社交和焦虑样表型恢复正常。重要的是，神经发生区域的大多数标记细胞显示放射状胶质细胞表型，而一群新生细胞表达早期神经元标志物TOAD或mGLuR5，后者表明代谢型谷氨酸受体5可能参与神经发生事件。
总体而言，我们的结果表明放射状胶质细胞增殖在许多神经精神疾病中观察到的焦虑和社交障碍重叠病理中起作用，并且可能代表改善这些症状的潜在新靶点。
