Castillo-Gómez Esther, Varea Emilio, Blasco-Ibáñez José Miguel, Crespo Carlos, Nacher Juan
Neurobiology Unit, BIOTECMED, Cell Biology Department, Universitat de València, 46100 Burjassot, Spain.
Neurobiology Unit, BIOTECMED, Cell Biology Department, Universitat de València, 46100 Burjassot, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, 46010 Valencia, Spain; CIBERSAM, Centro de Investigación Biomédica en Red Salud Mental, 28029 Madrid, Spain.
Neural Plast. 2016;2016:1615363. doi: 10.1155/2016/1615363. Epub 2016 Mar 23.
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found.
内侧前额叶皮质（mPFC）中的多巴胺D2受体（D2R）是精神分裂症病因学和治疗学中的关键因素。这些受体的过度激活会导致mPFC功能障碍。用D2R激动剂进行长期治疗会改变与神经元结构可塑性、突触功能和抑制性神经传递相关的分子表达，而这些在精神分裂症中也会发生改变。这些变化依赖于神经细胞黏附分子（PSA-NCAM）多唾液酸化形式的表达，PSA-NCAM是一种与可塑性相关的分子，但关于D2R和PSA-NCAM对兴奋性神经传递以及mPFC锥体神经元结构的影响，目前尚不清楚，而这两个特征在精神分裂症中也会受到影响。为了评估这些参数，我们在用内切酶N酶解去除PSA后，用PPHT（一种D2R激动剂）对成年大鼠进行了长期治疗。两种处理均降低了锥体神经元顶端树突的棘密度，而不影响其抑制性神经支配。内切酶N还降低了囊泡谷氨酸转运体-1的表达。这些结果表明，D2R和PSA-NCAM是调节mPFC兴奋性神经元结构可塑性的重要因素。这与我们对精神分裂症神经生物学基础的理解相关，在精神分裂症中已发现锥体神经元的结构改变以及D2R和PSA-NCAM的表达改变。
