Uehara Takashi, Sumiyoshi Tomiki, Seo Tomonori, Matsuoka Tadasu, Itoh Hiroko, Kurachi Masayoshi
Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan ; Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians University of Munich, Nußbaumstraße 7, 80336 Munich, Germany.
ISRN Psychiatry. 2012 Jul 8;2012:947149. doi: 10.5402/2012/947149. Print 2012.
The number of parvalbumin (PV)-positive γ -aminobutyric acid (GABA) neurons is decreased in the brain of rats transiently exposed to MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in the neonatal stage (Uehara et al. (2012)). T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate] is a neuroprotective agent synthesized for the treatment of psychiatric disorders characterized by cognitive disturbances, such as dementia. We herein sought to determine whether T-817MA, haloperidol (HPD), or risperidone (RPD) would ameliorate the decrease in the number of PV-positive GABA neurons in the medial prefrontal cortex (mPFC) and hippocampus of the model animals. Rats were treated with MK-801 (0.2 mg/kg/day) or vehicle on postnatal days (PD) 7-10, and the number of PV-positive neurons in the mPFC and hippocampus were measured on PDs 63. T-817MA (20 mg/kg), HPD (1 mg/kg), or RPD (1 mg/kg) were administered during PDs 49-62. Fourteen-day administration of T-817MA reversed the decrease in the number of PV-positive neurons in the above brain regions of rats given MK-801, whereas HPD and RPD were ineffective. These results indicate that T-817MA provides a novel pharmacologic strategy to enhance cognitive function in patients with schizophrenia.
在新生期短暂暴露于N-甲基-D-天冬氨酸（NMDA）受体阻滞剂MK-801的大鼠脑中，小清蛋白（PV）阳性γ-氨基丁酸（GABA）神经元的数量会减少（上原等人，2012年）。T-817MA [1-{3-[2-(1-苯并噻吩-5-基)乙氧基]丙基}氮杂环丁烷-3-醇马来酸盐]是一种合成的神经保护剂，用于治疗以认知障碍为特征的精神疾病，如痴呆症。我们在此试图确定T-817MA、氟哌啶醇（HPD）或利培酮（RPD）是否能改善模型动物内侧前额叶皮质（mPFC）和海马体中PV阳性GABA神经元数量的减少。在出生后第7至10天，给大鼠注射MK-801（0.2 mg/kg/天）或溶剂，在出生后第63天测量mPFC和海马体中PV阳性神经元的数量。在出生后第49至62天给予T-817MA（20 mg/kg）、HPD（1 mg/kg）或RPD（1 mg/kg）。连续14天给予T-817MA可逆转给予MK-801的大鼠上述脑区中PV阳性神经元数量的减少，而HPD和RPD则无效。这些结果表明，T-817MA为增强精神分裂症患者的认知功能提供了一种新的药理学策略。
