Valuskova Paulina, Farar Vladimir, Janisova Katerina, Ondicova Katarina, Mravec Boris, Kvetnansky Richard, Myslivecek Jaromir
a Institute of Physiology, 1st Faculty of Medicine , Charles University , Prague , Czech Republic.
b Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine , Charles University , Prague , Czech Republic.
Stress. 2017 Jan;20(1):36-43. doi: 10.1080/10253890.2016.1263836. Epub 2016 Dec 6.
Brain acetylcholinesterase (AChE) variant AChE expression increases with acute stress, and this persists for an extended period, although the timing, strain and laterality differences, have not been explored previously. Acute stress transiently increases acetylcholine release, which in turn may increase activity of cholinesterases. Also the AChE gene contains a glucocorticoid response element (GRE), and stress-inducible AChE transcription and activity changes are linked to increased glucocorticoid levels. Corticotropin-releasing hormone knockout (CRH-KO) mice have basal glucocorticoid levels similar to wild type (WT) mice, but much lower levels during stress. Hence we hypothesized that CRH is important for the cholinesterase stress responses, including butyrylcholinesterase (BChE). We used immobilization stress, acute (30 or 120 min) and repeated (120 min daily × 7) in 48 male mice (24 WT and 24 CRH-KO) and determined AChE, AChE and BChE mRNA expression and AChE and BChE activities in left and right brain areas (as cholinergic signaling shows laterality). Immobilization decreased BChE mRNA expression (right amygdala, to 0.5, 0.3 and 0.4, × control respectively) and AChE mRNA expression (to 0.5, 0.4 and 0.4, × control respectively). AChE mRNA expression increased (1.3, 1.4 and 1.8-fold, respectively) in the left striatum (Str). The AChE activity increased in left Str (after 30 min, 1.2-fold), decreased in right parietal cortex with repeated stress (to 0.5 × control). BChE activity decreased after 30 min in the right CA3 region (to 0.4 × control) but increased (3.8-fold) after 120 min in the left CA3 region. The pattern of changes in CRH-KO differed from that in WT mice.
脑乙酰胆碱酯酶（AChE）变体AChE的表达会随着急性应激而增加，并且这种增加会持续较长时间，尽管此前尚未探究过其时间、品系和脑区差异。急性应激会短暂增加乙酰胆碱的释放，这反过来可能会增加胆碱酯酶的活性。此外，AChE基因包含一个糖皮质激素反应元件（GRE），应激诱导的AChE转录和活性变化与糖皮质激素水平升高有关。促肾上腺皮质激素释放激素基因敲除（CRH-KO）小鼠的基础糖皮质激素水平与野生型（WT）小鼠相似，但在应激期间水平要低得多。因此，我们推测CRH对胆碱酯酶应激反应很重要，包括丁酰胆碱酯酶（BChE）。我们对48只雄性小鼠（24只WT和24只CRH-KO）施加急性（30或120分钟）和重复（每天120分钟×7天）的固定应激，然后测定左右脑区的AChE、AChE和BChE mRNA表达以及AChE和BChE活性（因为胆碱能信号显示出脑区差异）。固定应激降低了BChE mRNA表达（右杏仁核分别降至对照的0.5、0.3和0.4倍）和AChE mRNA表达（分别降至对照的0.5、0.4和0.4倍）。左纹状体（Str）中的AChE mRNA表达增加（分别为1.3、1.4和1.8倍）。AChE活性在左Str中增加（30分钟后为1.2倍），在右顶叶皮质中随着重复应激而降低（降至对照的0.5倍）。右CA3区在30分钟后BChE活性降低（降至对照的0.4倍），但左CA3区在120分钟后增加（3.8倍）。CRH-KO小鼠的变化模式与WT小鼠不同。
