Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Schizophr Bull. 2024 Jan 1;50(1):120-131. doi: 10.1093/schbul/sbad078.
Treatment of schizophrenia remains a major challenge. Recent studies have focused on glutamatergic signaling hypoactivity through N-methyl-D-aspartate (NMDA) receptors. Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The aim of this study was to investigate the efficacy of LIPUS against psychiatric symptoms and anxiety-like behaviors.
Rats assigned to 4 groups were pretreated with or without LIPUS for 5 days. The open field and prepulse inhibition tests were performed after saline or MK-801 (0.3 mg/kg) administration. Then, the neuroprotective effects of LIPUS on the MK-801-treated rats were evaluated using western blotting and immunohistochemical staining.
LIPUS stimulation of the prefrontal cortex (PFC) prevented deficits in locomotor activity and sensorimotor gating and improved anxiety-like behavior. MK-801 downregulated the expression of NR1, the NMDA receptor, in rat medial PFC (mPFC). NR1 expression was significantly higher in animals receiving LIPUS pretreatment compared to those receiving only MK-801. In contrast, a significant increase in c-Fos-positive cells in the mPFC and ventral tegmental area was observed in the MK-801-treated rats compared to those receiving only saline; this change was suppressed by pretreatment with LIPUS.
This study provides new evidence for the role of LIPUS stimulation in regulating the NMDA receptor and modulating c-Fos activity, which makes it a potentially valuable antipsychotic treatment for schizophrenia.
精神分裂症的治疗仍然是一个主要挑战。最近的研究集中在通过 N-甲基-D-天冬氨酸（NMDA）受体的谷氨酸能信号传递活性低下。低强度脉冲超声（LIPUS）改善了地卓西平（MK-801）治疗的大鼠的行为缺陷和神经病理学。本研究旨在探讨 LIPUS 对精神症状和焦虑样行为的疗效。
将大鼠分为 4 组，用或不用 LIPUS 预处理 5 天。在给予盐水或 MK-801（0.3mg/kg）后进行旷场和前脉冲抑制测试。然后，使用 Western 印迹和免疫组织化学染色评估 LIPUS 对 MK-801 治疗大鼠的神经保护作用。
LIPUS 刺激前额叶皮层（PFC）可防止运动活动和感觉运动门控缺陷，并改善焦虑样行为。MK-801 下调了大鼠内侧前额叶皮质（mPFC）中 NMDA 受体 NR1 的表达。与仅接受 MK-801 的动物相比，接受 LIPUS 预处理的动物的 NR1 表达明显更高。相反，与仅接受盐水的大鼠相比，MK-801 治疗的大鼠的 mPFC 和腹侧被盖区中的 c-Fos 阳性细胞显著增加；这种变化被 LIPUS 预处理所抑制。
本研究为 LIPUS 刺激调节 NMDA 受体和调节 c-Fos 活性的作用提供了新的证据，使其成为一种有价值的治疗精神分裂症的潜在抗精神病药物。
