Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, México; Laboratorio de Fisiología de la Conducta, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México.
Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, México.
Neuroscience. 2019 Jan 1;396:36-45. doi: 10.1016/j.neuroscience.2018.11.006. Epub 2018 Nov 16.
Schizophrenia is a neurodevelopmental disorder identified by psychotic episodes, as well as cognitive deficits. There are reports of multiple alterations in the brain in schizophrenia, such as fewer dendritic spines with shape abnormalities in cortical and subcortical areas. A correlation has been established between shape and function in dendritic spines; and as the main site of excitatory synapses, the dendritic spine pathology represents a potential target for novel therapeutic tools in schizophrenia. Neonatal ventral hippocampus lesion (nVHL) in the rat has been extensively used to examine some of the pathophysiological mechanisms of schizophrenia since it mimics several behaviors, as well as abnormalities in morphological corticolimbic neurons. Thus, in this report, we determined the effects of the nVHL on locomotor behavior and memory in postpubertal rats. Also, we explored the density and the dynamics of the dendritic spines in the pyramidal neurons of layers 3 and 5 of the prefrontal cortex (PFC) and basolateral amygdala (BLA), and also in the nucleus accumbens (NAcc) medium spiny neurons (MSN). We found that nVHL rats have exhibited both hyperlocomotion and memory deficits. nVHL also reduced the number of dendritic spines and decreased the proportion of mature spines in these neurons. In conclusion, nVHL triggers behavioral abnormalities in postpubertal rats that can be associated not only with the lack of dendritic spines but also with distortion of these structures in corticolimbic neurons. Hence, the nVHL can be useful to explore the mechanisms of the dendritic spine pathology and its implications for schizophrenia.
精神分裂症是一种神经发育障碍，其特征是出现精神病发作和认知缺陷。有报道称，精神分裂症患者的大脑存在多种改变，例如皮质和皮质下区域的树突棘数量减少且形态异常。树突棘的形态和功能之间存在相关性；作为兴奋性突触的主要部位，树突棘病理学代表了精神分裂症新型治疗工具的潜在靶点。新生大鼠腹侧海马损伤（nVHL）在大鼠中被广泛用于研究精神分裂症的一些病理生理机制，因为它可以模拟多种行为以及皮质边缘神经元的形态异常。因此，在本报告中，我们确定了 nVHL 对青春期后大鼠运动行为和记忆的影响。此外，我们还研究了前额叶皮层（PFC）和外侧杏仁核（BLA）以及伏隔核（NAcc）中的锥体神经元以及中间神经元树突棘的密度和动态。我们发现 nVHL 大鼠表现出过度活跃和记忆缺陷。nVHL 还减少了这些神经元中树突棘的数量，并降低了成熟树突棘的比例。总之，nVHL 会引发青春期后大鼠的行为异常，这些异常不仅与树突棘缺失有关，还与皮质边缘神经元中这些结构的扭曲有关。因此，nVHL 可用于探索树突棘病理学的机制及其对精神分裂症的影响。
