Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment

Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment
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DOI:
10.1016/s0304-3940(96)13213-4
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发表时间:
1996-12-13
影响因子:
2.5
通讯作者:
Angulo, JA
Angulo, JA
中科院分区:
医学4区
文献类型:
--
作者:
Datta, U;Noailles, PAH;Angulo, JA

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在本研究中,我们评估了慢性治疗与咖啡因的水平上的信使RNA分子编码的酶酪氨酸羟化酶(TH)的原位杂交组织化学在腹侧被盖区(VTA)和黑质的大鼠大脑(SNc)。以20、40和80 mg/kg体重的剂量连续9天接受咖啡因的动物在SNc(比注射载体的对照组高64%)和VTA(比对照组高33%)中显示出TH mRNA水平增加。此外,同时给予非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂MK-801(0.25 mg/kg)可预防80 mg/kg咖啡因剂量下观察到的增加。这些结果表明,长期暴露于咖啡因,腺苷A2受体拮抗剂,改变的mRNA编码的速率限制酶的儿茶酚胺生物合成的表达水平。版权所有(C)1996 Elsevier Science爱尔兰有限公司
In the present study we assessed the effect of chronic treatment with caffeine on the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA) and the substantia nigra compacta (SNc) of the rat brain. Animals that received caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected controls) and the VTA (33% above controls). Moreover, the increases observed at 80 mg/kg of caffeine were prevented by concurrent administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg). These results demonstrate that chronic exposure to caffeine, an adenosine A2 receptor antagonist, alters the levels of expression of the mRNA encoding the rate limiting enzyme in catecholamine biosynthesis. Copyright (C) 1996 Elsevier Science Ireland Ltd.