Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
Bipolar Disord. 2009 Nov;11(7):711-25. doi: 10.1111/j.1399-5618.2009.00752.x.
Altered glutamate transmission has been found in the medial temporal lobe in severe psychiatric illnesses, including major depressive disorder (MDD) and bipolar disorder (BD). The vesicular glutamate transporters (VGLUTs) have a pivotal role in presynaptic release of glutamate into the synaptic cleft. We investigated this presynaptic marker in major psychiatric illness by measuring transcript expression of the VGLUTs in the medial temporal lobe.
The study sample comprised four groups of 13 subjects with MDD, BD, or schizophrenia (SCZ), and a comparison group from the Stanley Foundation Neuropathology Consortium. In situ hybridization was performed to quantify messenger RNA (mRNA) expression of VGLUT 1, 2, and 3 in medial temporal lobe structures. We also examined the same areas of rats treated with antidepressants, a mood stabilizer, and antipsychotics to assess the effects of these medications on VGLUT mRNA expression.
We found decreased VGLUT1 mRNA expression in both MDD and BD in the entorhinal cortex (ERC), decreased VGLUT2 mRNA expression in MDD in the middle temporal gyrus, and increased VGLUT2 mRNA expression in SCZ in the inferior temporal gyrus (ITG). We also found a negative correlation between age and VGLUT1 mRNA expression in BD in the ERC and ITG. We did not find any changes in VGLUT mRNA expression in the hippocampus in any diagnostic group. We found decreased VGLUT1 mRNA expression in rats treated with haloperidol in the temporal cortex.
These data indicate region-specific alterations of presynaptic glutamate innervation in the medial temporal lobe in the mood disorders.
谷氨酸传递的改变已在包括重度精神疾病(如重度抑郁障碍和双相情感障碍)在内的内侧颞叶中被发现。囊泡谷氨酸转运体(VGLUTs)在谷氨酸的前突触释放到突触间隙中起着关键作用。我们通过测量内侧颞叶中 VGLUT 的转录表达来研究这个前突触标记物在主要精神疾病中的作用。
研究样本包括四组各 13 名患有 MDD、BD 或精神分裂症(SCZ)的受试者,以及来自 Stanley 基金会神经病理学联合会的对照组。通过原位杂交来定量内侧颞叶结构中 VGLUT1、2 和 3 的信使 RNA(mRNA)表达。我们还检查了接受抗抑郁药、心境稳定剂和抗精神病药治疗的大鼠的相同区域,以评估这些药物对 VGLUT mRNA 表达的影响。
我们发现 MDD 和 BD 中的 VGLUT1 mRNA 表达在齿状回(ERC)中减少,MDD 中的 VGLUT2 mRNA 表达在中颞叶中减少,SCZ 中的 VGLUT2 mRNA 表达在颞下回(ITG)中增加。我们还发现 BD 中的 ERC 和 ITG 中 VGLUT1 mRNA 表达与年龄呈负相关。我们在任何诊断组中都没有发现海马区 VGLUT mRNA 表达的变化。我们发现,在颞皮质中接受氟哌啶醇治疗的大鼠的 VGLUT1 mRNA 表达减少。
这些数据表明,在心境障碍中,内侧颞叶的前突触谷氨酸传入存在特定区域的改变。