Department of Anatomy and Neuroscience, University College Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Ireland, University College Cork, Ireland.
Brain Behav Immun. 2020 Jan;83:172-179. doi: 10.1016/j.bbi.2019.10.007. Epub 2019 Oct 8.
Both neuroinflammation and adult hippocampal neurogenesis (AHN) are implicated in many neurodegenerative disorders as well as in neuropsychiatric disorders, which often become symptomatic during adolescence. A better knowledge of the impact that chronic neuroinflammation has on the hippocampus during the adolescent period could lead to the discovery of new therapeutics for some of these disorders. The hippocampus is particularly vulnerable to altered concentrations of the pro-inflammatory cytokine interleukin-1β (IL-1β), with elevated levels implicated in the aetiology of neurodegenerative disorders such as Alzheimer's and Parkinson's, and stress-related disorders such as depression. The effect of acutely and chronically elevated concentrations of hippocampal IL-1β have been shown to reduce AHN in adult rodents. However, the effect of exposure to chronic overexpression of hippocampal IL-1β during adolescence, a time of increased vulnerability, hasn't been fully interrogated. Thus, in this study we utilized a lentiviral approach to induce chronic overexpression of IL-1β in the dorsal hippocampus of adolescent male Sprague Dawley rats for 5 weeks, during which time its impact on cognition and hippocampal neurogenesis were examined. A reduction in hippocampal neurogenesis was observed along with a reduced level of neurite branching on hippocampal neurons. However, there was no effect of IL-1β overexpression on performance in pattern separation, novel object recognition or spontaneous alternation in the Y maze. Our study has highlighted that chronic IL-1β overexpression in the hippocampus during the adolescent period exerts a negative impact on neurogenesis independent of cognitive performance, and suggests a degree of resilience of the adolescent hippocampus to inflammatory insult.
神经炎症和成年海马神经发生（AHN）都与许多神经退行性疾病以及神经精神疾病有关，这些疾病通常在青春期出现症状。更好地了解慢性神经炎症对青春期海马的影响可能会为这些疾病中的一些发现新的治疗方法。海马体特别容易受到促炎细胞因子白细胞介素-1β（IL-1β）浓度变化的影响，其水平升高与阿尔茨海默病和帕金森病等神经退行性疾病以及抑郁等与应激相关的疾病的病因有关。已经表明，海马体中 IL-1β 的浓度急性和慢性升高会减少成年啮齿动物的 AHN。然而，在易受伤害增加的青春期期间暴露于海马体 IL-1β 的慢性过表达的影响尚未得到充分研究。因此，在这项研究中，我们利用慢病毒方法在青春期雄性 Sprague Dawley 大鼠的背侧海马体中慢性过表达 IL-1β 5 周，在此期间检查其对认知和海马神经发生的影响。观察到海马神经发生减少，同时海马神经元的分枝神经突水平降低。然而，IL-1β 过表达对模式分离、新物体识别或 Y 迷宫中的自发交替没有影响。我们的研究强调，青春期海马体中慢性 IL-1β 过表达对神经发生有负面影响，而与认知表现无关，并表明青春期海马体对炎症损伤具有一定的恢复力。
