Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
PLoS One. 2013 Apr 8;8(4):e59320. doi: 10.1371/journal.pone.0059320. Print 2013.
Reports indicate that PDLIM5 is involved in mood disorders. The PDLIM5 (PDZ and LIM domain 5) gene has been genetically associated with mood disorders; it's expression is upregulated in the postmortem brains of patients with bipolar disorder and downregulated in the peripheral lymphocytes of patients with major depression. Acute and chronic methamphetamine (METH) administration may model mania and the evolution of mania into psychotic mania or schizophrenia-like behavioral changes, respectively.
To address whether the downregulation of PDLIM5 protects against manic symptoms and cause susceptibility to depressive symptoms, we evaluated the effects of reduced Pdlim5 levels on acute and chronic METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming by using Pdlim5 hetero knockout (KO) mice.
The homozygous KO of Pdlim5 is embryonic lethal. The effects of METH administration on locomotor hyperactivity and the impairment of prepulse inhibition were lower in Pdlim5 hetero KO mice than in wild-type mice. The transient inhibition of PDLIM5 (achieved by blocking the translocation of protein kinase C epsilon before the METH challenge) had a similar effect on behavior. Pdlim5 hetero KO mice showed increased immobility time in the forced swimming test, which was diminished after the chronic administration of imipramine. Chronic METH treatment increased, whereas chronic haloperidol treatment decreased, Pdlim5 mRNA levels in the prefrontal cortex. Imipramine increased Pdlim5 mRNA levels in the hippocampus.
These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.
有报道称 PDLIM5 与心境障碍有关。PDLIM5（PDZ 和 LIM 域 5）基因与心境障碍有遗传关联；其在双相情感障碍患者的死后大脑中表达上调，在重度抑郁症患者的外周淋巴细胞中表达下调。急性和慢性 methamphetamine（METH）给药可能分别模拟躁狂症以及躁狂症向精神病性躁狂或精神分裂样行为改变的发展。
为了确定 PDLIM5 的下调是否能预防躁狂症状并导致易患抑郁症状，我们使用 Pdlim5 杂合 KO 小鼠评估了降低 Pdlim5 水平对急性和慢性 METH 诱导的运动过度、条件性恐惧反射抑制和强迫游泳的影响。
Pdlim5 的纯合 KO 是胚胎致死的。METH 给药对运动过度和条件性恐惧反射抑制的影响在 Pdlim5 杂合 KO 小鼠中低于野生型小鼠。PDLIM5 的瞬时抑制（通过在 METH 挑战前阻止蛋白激酶 C epsilon 的易位来实现）对行为也有类似的影响。Pdlim5 杂合 KO 小鼠在强迫游泳试验中表现出的不动时间增加，在慢性给予丙咪嗪后减少。慢性 METH 处理增加，而慢性氟哌啶醇处理减少，前额叶皮层中的 Pdlim5 mRNA 水平。丙咪嗪增加了海马中的 Pdlim5 mRNA 水平。
这些发现与人类报告的观察结果部分一致，表明 PDLIM5 参与了包括心境障碍在内的精神疾病。
