Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Von-Siebold-Strasse 5, D-37075 Göttingen, Germany.
Curr Pharm Biotechnol. 2012 Jun;13(8):1595-605. doi: 10.2174/138920112800784763.
Schizophrenia is a brain disorder associated with subtle, but replicable cerebral volume loss mostly prevalent in frontal and temporal brain regions. Post-mortem studies of the hippocampus point to a reduction of the neuropil constituting mainly of synapses associated with changes of molecules mediating plastic responses of neurons during development and learning. Derived from animal studies interventions to enhance neuroplasticity by inducing adult neurogenesis, synaptogenesis, angiogenesis and long-term potentiation (LTP) were developed and the results translated into clinical studies in schizophrenia. Out of these interventions aerobic exercise has been shown to increase hippocampal volume, elevate N-acetyl-aspartate in the hippocampus as neuronal marker, and improve short-term memory in schizophrenia. The hematopoietic growth factor erythropoetin (EPO) is involved in brain development and associated with the production and differentiation of neuronal precursor cells. A first study demonstrated a positive effect of EPO application on cognition in schizophrenia patients. In randomised controlled studies with small sample size, the efficacy of repetitive transcranial magnetic stimulation (rTMS), a biological intervention focussing on the enhancement of LTP, has been shown for the improvement of positive and negative symptoms in schizophrenia,. The putative underlying neurobiological mechanisms of these interventions including the role of neurotrophic factors are outlined and implications for future research regarding neuroprotection strategies to improve schizophrenia are discussed.
精神分裂症是一种与脑体积轻微但可复制性损失相关的脑部疾病，主要发生在前额和颞叶区域。对海马体的尸检研究表明，神经突起减少，主要由与神经元发育和学习过程中可塑性反应的分子变化相关的突触组成。从动物研究中得出的干预措施，通过诱导成年神经发生、突触发生、血管生成和长时程增强（LTP）来增强神经可塑性，并将这些结果转化为精神分裂症的临床研究。在这些干预措施中，有氧运动已被证明可以增加海马体体积、提高海马体中的 N-乙酰天冬氨酸（作为神经元标志物），并改善精神分裂症患者的短期记忆。造血生长因子促红细胞生成素（EPO）参与脑发育，并与神经元前体细胞的产生和分化有关。第一项研究表明，EPO 应用对精神分裂症患者的认知有积极影响。在随机对照研究中，重复经颅磁刺激（rTMS）作为一种关注 LTP 增强的生物学干预措施，其疗效已被证明可改善精神分裂症的阳性和阴性症状。概述了这些干预措施的潜在神经生物学机制，包括神经营养因子的作用，并讨论了针对改善精神分裂症的神经保护策略的未来研究的意义。
