Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain.
Neurobiol Aging. 2012 Apr;33(4):827.e1-9. doi: 10.1016/j.neurobiolaging.2011.06.011. Epub 2011 Jul 27.
This study investigated the role of the dorsomedial prefrontal cortex (dmPFC) on the activity of the hypothalamus-pituitary-adrenal axis and memory consolidation in young and aged rats. The messenger RNA (mRNA) expression of several gamma-aminobutyric acid (GABA) and glutamate receptor subunits were also evaluated in the prefrontal cortex (PFC) of young and aged rats. Microinjections of picrotoxin (GABA(A) antagonist), muscimol (GABA(A) agonist), or vehicle were performed into the dmPFC of young adult (3 months) and aged (27 months) male Wistar rats. Plasma corticosterone was measured under acute stress (30-minute restraint) conditions following microinjections. The retention of an inhibitory avoidance response was also evaluated in response of the same treatments. Picrotoxin microinjections into the dmPFC reduced the stress-induced corticosterone concentrations on young but not on aged animals. Aging did not modify the mRNA content of any of the receptor subunits analyzed. Picrotoxin into the dmPFC reduced inhibitory avoidance response in young but not aged animals. Muscimol treatment did not modify any of the parameters evaluated. These results suggest that prefrontal cortex loses its capacity to control hypothalamo-pituitary-adrenal (HPA) axis activity and the consolidation of emotional memory during aging.
本研究探讨了背内侧前额叶皮层（dmPFC）在年轻和老年大鼠下丘脑-垂体-肾上腺轴（HPA 轴）活动和记忆巩固中的作用。还评估了年轻和老年大鼠前额叶皮层（PFC）中几种γ-氨基丁酸（GABA）和谷氨酸受体亚基的信使 RNA（mRNA）表达。将苦味酸毒素（GABA(A) 拮抗剂）、muscimol（GABA(A) 激动剂）或载体微注射到年轻成年（3 个月）和老年（27 个月）雄性 Wistar 大鼠的 dmPFC 中。在微注射后进行急性应激（30 分钟束缚）条件下测量血浆皮质酮。还评估了相同处理对抑制性回避反应的保留情况。dmPFC 中的苦味酸毒素微注射降低了年轻但不降低老年动物的应激诱导的皮质酮浓度。衰老并没有改变分析的任何受体亚基的 mRNA 含量。dmPFC 中的苦味酸毒素微注射降低了年轻但不降低老年动物的抑制性回避反应。Muscimol 处理没有改变任何评估的参数。这些结果表明，前额叶皮层在衰老过程中丧失了控制下丘脑-垂体-肾上腺（HPA）轴活动和情绪记忆巩固的能力。
