Laboratory of Neurobiology, Centro de Investigaciones Medico Sanitaria (CIMES), University of Malaga, Malaga, Spain.
Department of Medicine, University of Malaga, Malaga, Spain.
FASEB J. 2019 Nov;33(11):11804-11820. doi: 10.1096/fj.201900429RR. Epub 2019 Jul 31.
Memory deficits affect a large proportion of the human population and are associated with aging and many neurologic, neurodegenerative, and psychiatric diseases. Treatment of this mental disorder has been disappointing because all potential candidates studied thus far have failed to produce consistent effects across various types of memory and have shown limited to no effects on memory deficits. Here, we show that the promotion of neuronal arborization through the expression of the regulator of G-protein signaling 14 of 414 amino acids (RGS14) not only induced robust enhancement of multiple types of memory but was also sufficient for the recovery of recognition, spatial, and temporal memory, which are kinds of episodic memory that are primarily affected in patients or individuals with memory dysfunction. We observed that a surge in neuronal arborization was mediated by up-regulation of brain-derived neurotrophic factor (BDNF) signaling and that the deletion of BDNF abrogated both neuronal arborization activation and memory enhancement. The activation of BDNF-dependent neuronal arborization generated almost 2-fold increases in synapse numbers in dendrites of pyramidal neurons and in neurites of nonpyramidal neurons. This increase in synaptic connections might have evoked reorganization within neuronal circuits and eventually supported an increase in the activity of such circuits. Thus, in addition to showing the potential of RGS14 for rescuing memory deficits, our results suggest that a boost in circuit activity could facilitate memory enhancement and the reversal of memory deficits.-Masmudi-Martín, M., Navarro-Lobato, I., López-Aranda, M. F., Delgado, G., Martín-Montañez, E., Quiros-Ortega, M. E., Carretero-Rey, M., Narváez, L., Garcia-Garrido, M. F., Posadas, S., López-Téllez, J. F., Blanco, E., Jiménez-Recuerda, I., Granados-Durán, P., Paez-Rueda, J., López, J. C., Khan, Z. U. RGS14 treatment induces memory enhancement and rescues episodic memory deficits.
记忆缺陷影响了很大一部分人群，与衰老以及许多神经退行性和精神疾病有关。这种精神障碍的治疗一直令人失望，因为迄今为止研究的所有潜在候选药物都未能在各种类型的记忆中产生一致的效果，并且对记忆缺陷的影响也有限。在这里，我们表明，通过表达 414 个氨基酸的 G 蛋白信号调节因子 14（RGS14）促进神经元树突分支不仅会强烈增强多种类型的记忆，而且足以恢复识别，空间和时间记忆，这是在患者或记忆功能障碍个体中主要受影响的情景记忆。我们观察到，神经元树突分支的激增是通过上调脑源性神经营养因子（BDNF）信号介导的，而 BDNF 的缺失既消除了神经元树突分支的激活，也消除了记忆增强。BDNF 依赖性神经元树突分支的激活使锥体神经元的树突和非锥体神经元的神经突中的突触数量增加了近 2 倍。这种突触连接的增加可能引发了神经元回路内的重组，最终支持了这些回路活性的增加。因此，除了显示 RGS14 具有挽救记忆缺陷的潜力外，我们的研究结果还表明，增加回路活动可以促进记忆增强和记忆缺陷的逆转。-Masmudi-Martín，M.，Navarro-Lobato，I.，López-Aranda，M. F.，Delgado，G.，Martín-Montañez，E.，Quiros-Ortega，M. E.，Carretero-Rey，M.，Narváez，L.，Garcia-Garrido，M. F.，Posadas，S.，López-Téllez，J. F.，Blanco，E.，Jiménez-Recuerda，I.，Granados-Durán，P.，Paez-Rueda，J.，López，J. C.，Khan，Z. U. RGS14 治疗可增强记忆并挽救情景记忆缺陷。
