Developmental suppression of forebrain trkA receptors and attentional capacities in aging rats: A longitudinal study.
Developmental suppression of forebrain trkA receptors and attentional capacities in aging rats: A longitudinal study.
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DOI：
10.1016/j.bbr.2017.08.017
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发表时间：
2017-09-29
影响因子：
2.7
通讯作者：
Parikh V
中科院分区：
文献类型：
--
作者：
Yegla B;Parikh V
基底前脑（BF）胆碱能神经元支配皮质调节认知，特别是注意，过程。胆碱能萎缩和认知能力下降在老年性神经退行性疾病（如阿尔茨海默病）中以加速的速度发生;然而，导致这种现象的机制仍然未知。在这里，我们假设，通过原肌球蛋白相关激酶A（trkA）受体介导的神经生长因子信号的发育抑制，将加剧与年龄相关的注意力脆弱性。表达trkA shRNA的腺相关病毒载体（AAV-trkA）被用来敲低出生后大鼠的trkA受体在个体发育的时间点时，皮质胆碱能输入成熟，这种操作对性能的影响进行了评估，在动物保持在一个操作性注意力任务，整个成年期，直到老年（24个月）。不同时间点的受试者内比较表明，注意力能力逐渐随年龄下降。然而，在任何时间点，在基线和分心条件下的性能在AAV-trkA输注的动物和用表达针对对照蛋白质荧光素酶的shRNA的载体输注的动物之间没有差异。在24个月时进行的胆碱能测量的附加分析表明，胆碱能末梢在去极化刺激后释放乙酰胆碱的能力、皮质胆碱能纤维密度和BF胆碱能细胞大小在两组之间保持相当。与我们的预测相反，这些数据表明，发展BF trkA中断不影响注意力功能的年龄相关的变化。终身从事认知活动可能有可能挽救了对胆碱能系统的发育损伤，从而保留了老年人的注意力。
Basal forebrain (BF) cholinergic neurons innervating the cortex regulate cognitive, specifically attentional, processes. Cholinergic atrophy and cognitive decline occur at an accelerated pace in age-related neurodegenerative disorders such as Alzheimer’s disease; however, the mechanism responsible for this phenomenon remains unknown. Here we hypothesized that developmental suppression of nerve growth factor signaling, mediated via tropomyosin-related kinase A (trkA) receptors, would escalate age-related attentional vulnerability. An adeno-associated viral vector expressing trkA shRNA (AAV-trkA) was utilized to knockdown trkA receptors in postnatal rats at an ontogenetic time point when cortical cholinergic inputs mature, and the impact of this manipulation on performance was assessed in animals maintained on an operant attention task throughout adulthood and until old (24 months) age. A within-subject comparison across different time points illustrated a gradual age-related decline in attentional capacities. However, the performance under baseline and distracted conditions did not differ between the AAV-trkA-infused and animals infused with a vector expressing shRNA against the control protein luciferase at any time point. Additional analysis of cholinergic measures conducted at 24 months showed that the capacity of cholinergic terminals to release acetylcholine following a depolarizing stimulus, cortical cholinergic fiber density and BF cholinergic cell size remained comparable between the two groups. Contrary to our predictions, these data indicate that developmental BF trkA disruption does not impact age-related changes in attentional functions. It is possible that life-long engagement in cognitive activity might have potentially rescued the developmental insults on the cholinergic system, thus preserving attentional capacities in advanced age.
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影响因子：
2.8
作者：
Counts SE;Che S;Ginsberg SD;Mufson EJ
通讯作者：
Mufson EJ
影响因子：
3.4
作者：
Al-Shawi, Raya;Hafner, Angela;Cowen, Timothy
通讯作者：
Cowen, Timothy
影响因子：
3.5
作者：
Fahnestock, M;Michalski, B;Coughlin, MD
通讯作者：
Coughlin, MD
影响因子：
4.2
作者：
Haense, Cathleen;Kalbe, Elke;Heiss, Wolf-Dieter
通讯作者：
Heiss, Wolf-Dieter
影响因子：
4.2
作者：
HARTIKKA, J;HEFTI, F
通讯作者：
HEFTI, F