Girard-Joyal Olivier, Ismail Nafissa
School of Psychology, University of Ottawa, Ottawa, ON, Canada.
School of Psychology, University of Ottawa, Ottawa, ON, Canada.
Horm Behav. 2017 Mar;89:1-12. doi: 10.1016/j.yhbeh.2016.12.009. Epub 2016 Dec 24.
Puberty is a critical period of development during which the brain undergoes reorganizing and remodeling. Exposure to stress during this period is thought to interfere with normal brain development and increase susceptibility to mental illnesses. In female mice, pubertal exposure to lipopolysaccharide (LPS), a bacterial endotoxin, has been shown to alter sexual, anxiety-like, and depression-like behaviors and cognition in an enduring manner. However, the mechanisms underlying these effects remain unknown. The present study examined age and sex difference in tyrosine hydroxylase (TH) expression and dopamine-dependent and Parkinson-like behaviors following LPS treatment. The results show that LPS treatment during adulthood causes an enduring increase in TH expression in many of the brain regions examined. In contrast, there is no change in TH expression following LPS treatment during puberty. However, pubertal LPS treatment induces enduring behavioral deficits in tests of Parkinson-like behaviors, more so in male than in female mice. These results suggest that the low levels of TH following exposure to pubertal immune challenge may predispose mice to Parkinson-like behavior. These findings add to our understanding of stress and immune responses during puberty and their impact on mental health later in life.
青春期是一个关键的发育时期,在此期间大脑会进行重组和重塑。人们认为,在此期间暴露于压力下会干扰大脑的正常发育,并增加患精神疾病的易感性。在雌性小鼠中,青春期暴露于脂多糖(LPS),一种细菌内毒素,已被证明会持久地改变性行为、焦虑样行为、抑郁样行为和认知。然而,这些影响背后的机制仍然未知。本研究检查了LPS处理后酪氨酸羟化酶(TH)表达、多巴胺依赖性和帕金森样行为的年龄和性别差异。结果表明,成年期LPS处理会导致在所检查的许多脑区中TH表达持久增加。相比之下,青春期LPS处理后TH表达没有变化。然而,青春期LPS处理会在帕金森样行为测试中诱导持久的行为缺陷,雄性小鼠比雌性小鼠更明显。这些结果表明,暴露于青春期免疫挑战后TH水平较低可能使小鼠易患帕金森样行为。这些发现增进了我们对青春期压力和免疫反应及其对后期心理健康影响的理解。