Department of Medical Technology, Kawasaki University of Medical Welfare, Okayama, 701-0193, Japan; Department of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama, 700-8558, Japan.
Life Science Research Center, University of Toyama, Toyama, 930-0194, Japan.
Neurochem Int. 2018 Jan;112:59-70. doi: 10.1016/j.neuint.2017.11.001. Epub 2017 Nov 7.
Cognitive function declines with age. Such function depends on γ-oscillation in the frontal cortex. Pyramidal neurons, and the parvalbumin-expressing interneurons (PV neurons) that control them, are important for the generation of γ-oscillation. The mechanism by which cognitive function declines is unclear. Perineuronal nets (PNNs) mainly surround the soma and proximal dendrites and axon segments of PV neurons in the cerebral cortex. Previous evidence indicates that PNNs inhibit neural plasticity. If this is true, an increase in the number of neurons surrounded by PNNs or in the thickness or density of the PNNs around neurons could decrease plasticity in the cortex. To determine if an aging-related change in cortical PNNs occurs, we examined the influence of aging on PV neurons and whether Wisteria floribunda agglutinin-positive PNNs differ depending on the cortical area. The results showed that the number of PV neurons/mm did not change in many areas of the cortex as mice aged. In contrast, the number of neurons in the sensory cortex surrounded by PNNs increased as mice aged. Thus, with age, PNN density increases in some cortical areas but not in others. In addition, the expression level of PV protein in PV neurons decreased with aging in the whole cortex. We suggest that decreased expression of PV protein impairs fast spiking in PV neurons. We propose that PNNs surround more neurons as age increases. This aging-related increase in PNNs decreases plasticity in the cerebral cortex and reduces cognitive function. The first step in investigating this proposal would be to determine if PNN density increases with age.
认知功能随年龄增长而下降。这种功能依赖于额叶皮层中的γ-振荡。控制 γ-振荡的锥体神经元和表达钙结合蛋白 Parvalbumin 的中间神经元(PV 神经元)对于 γ-振荡的产生非常重要。认知功能下降的机制尚不清楚。周围神经毡(PNNs)主要围绕大脑皮层中 PV 神经元的胞体和近端树突及轴突节段。先前的证据表明 PNNs 抑制神经可塑性。如果这是真的,那么被 PNNs 包围的神经元数量增加,或者 PNNs 围绕神经元的厚度或密度增加,都可能会降低皮层的可塑性。为了确定皮质 PNNs 是否会发生与衰老相关的变化,我们研究了衰老对 PV 神经元的影响,以及 Wisteria floribunda agglutinin 阳性 PNNs 是否因皮质区域而异。结果表明,随着小鼠年龄的增长,许多皮层区域的 PV 神经元/mm 数量没有变化。相比之下,随着小鼠年龄的增长,被 PNNs 包围的感觉皮层中的神经元数量增加。因此,随着年龄的增长,一些皮质区域的 PNN 密度增加,而另一些则没有。此外,整个皮层中 PV 神经元中 PV 蛋白的表达水平随年龄增长而降低。我们认为,PV 蛋白表达的降低会损害 PV 神经元的快速放电。我们提出,随着年龄的增长,PNNs 会包围更多的神经元。这种与年龄相关的 PNNs 增加会降低大脑皮层的可塑性,并降低认知功能。研究这一假说的第一步将是确定 PNN 密度是否随年龄增长而增加。