Guerra-Gomes Sónia, Viana João Filipe, Nascimento Diana Sofia Marques, Correia Joana Sofia, Sardinha Vanessa Morais, Caetano Inês, Sousa Nuno, Pinto Luísa, Oliveira João Filipe
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.
Front Cell Neurosci. 2018 Nov 5;12:379. doi: 10.3389/fncel.2018.00379. eCollection 2018.
Aging is a lifelong process characterized by cognitive decline putatively due to structural and functional changes of neural circuits of the brain. Neuron-glial signaling is a fundamental component of structure and function of circuits of the brain, and yet its possible role in aging remains elusive. Significantly, neuron-glial networks of the prefrontal cortex undergo age-related alterations that can affect cognitive function, and disruption of glial calcium signaling has been linked with cognitive performance. Motivated by these observations, we explored the possible role of glia in cognition during aging, considering a mouse model where astrocytes lacked IPR2-dependent Ca signaling. Contrarily to aged wild-type animals that showed significant impairment in a two-trial place recognition task, aged IPR2 KO mice did not. Consideration of neuronal and astrocytic cell densities in the prefrontal cortex, revealed that aged IPR2 KO mice present decreased densities of NeuN neurons and increased densities of S100β astrocytes. Moreover, aged IPR2 KO mice display refined dendritic trees in this region. These findings suggest a novel role for astrocytes in the aged brain. Further evaluation of the neuron-glial interactions in the aged brain will disclose novel strategies to handle healthy cognitive aging in humans.
衰老 是一个终身过程，其特征是认知能力下降，据推测这是由于大脑神经回路的结构和功能变化所致。神经元 - 胶质细胞信号传导是大脑回路结构和功能的基本组成部分，但其在衰老过程中可能发挥的作用仍不清楚。值得注意的是，前额叶皮质的神经元 - 胶质细胞网络会发生与年龄相关的改变，这可能会影响认知功能，而胶质细胞钙信号的破坏与认知表现有关。基于这些观察结果，我们以星形胶质细胞缺乏IPR2依赖性钙信号的小鼠模型为研究对象，探讨了衰老过程中胶质细胞在认知中的可能作用。与在两次试验地点识别任务中表现出明显损伤的老年野生型动物相反，老年IPR2基因敲除小鼠没有出现这种情况。对前额叶皮质中神经元和星形胶质细胞密度的研究表明，老年IPR2基因敲除小鼠的NeuN神经元密度降低，S100β星形胶质细胞密度增加。此外，老年IPR2基因敲除小鼠在该区域的树突分支更为精细。这些发现表明星形胶质细胞在老年大脑中具有新的作用。对老年大脑中神经元 - 胶质细胞相互作用的进一步评估将揭示应对人类健康认知衰老的新策略。
