Pegueros-Maldonado Rogelio, Pech-Pool Santiago M, Blancas Jaisson J, Prado-Alcalá Roberto A, Arámburo Carlos, Luna Maricela, Quirarte Gina L
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Front Behav Neurosci. 2024 Feb 26;18:1341883. doi: 10.3389/fnbeh.2024.1341883. eCollection 2024.
Corticosterone (CORT) release during learning experiences is associated with strong memories and activity of the glucocorticoid receptor. It has been shown that lesions of the dorsal striatum (DS) of rats trained in the cued version of the Morris water maze impair memory, and that local injection of CORT improves its performance, suggesting that DS activity is involved in procedural memory which may be modulated by CORT. We trained rats in cued Morris water maze and analyzed the effect of CORT synthesis inhibition on performance, CORT levels, expression of plasticity-involved genes, such as the brain derived neurotrophic factor (BDNF), casein kinase 2 (CK2), and the serum/glucocorticoid regulated kinase 1 (SGK1), as well as the presence of phosphorylated nuclear glucocorticoid receptor in serine 232 (pGR-S232) in the DS. The inhibition of CORT synthesis by metyrapone reduced CORT levels in plasma, prevented its increment in DS and impaired the performance of cued water maze. Additionally, there was an increase of CK2 and SGK1 mRNAs expression in trained subjects, which was unrelated to CORT levels. Finally, we did not observe changes in nuclear pGR-S232 in any condition. Our findings agree with evidence demonstrating that decreasing CORT levels hinders acquisition and consolidation of the spatial version of the Morris water maze; these novel findings broaden our knowledge about the involvement of the DS in the mechanisms underlying procedural memory.
在学习过程中,皮质酮(CORT)的释放与强烈的记忆以及糖皮质激素受体的活性相关。研究表明,在莫里斯水迷宫线索版本训练中大鼠的背侧纹状体(DS)损伤会损害记忆,而局部注射CORT可改善其表现,这表明DS的活性参与了程序性记忆,且该记忆可能受CORT调节。我们在莫里斯水迷宫线索版本中训练大鼠,并分析了CORT合成抑制对其表现、CORT水平、可塑性相关基因(如脑源性神经营养因子(BDNF)、酪蛋白激酶2(CK2)和血清/糖皮质激素调节激酶1(SGK1))的表达以及DS中丝氨酸232位点磷酸化核糖皮质激素受体(pGR-S232)存在情况的影响。美替拉酮对CORT合成的抑制降低了血浆中的CORT水平,阻止了其在DS中的升高,并损害了线索水迷宫的表现。此外,训练大鼠中CK2和SGK1 mRNA表达增加,这与CORT水平无关。最后,我们在任何条件下均未观察到核pGR-S232的变化。我们的研究结果与证据相符,即降低CORT水平会阻碍莫里斯水迷宫空间版本的获取和巩固;这些新发现拓宽了我们对DS参与程序性记忆潜在机制的认识。