Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus

Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus
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DOI:
10.1016/j.neuroscience.2005.02.021
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发表时间:
2005-01-01
期刊:
影响因子:
3.3
通讯作者:
Srivastava, LK
Srivastava, LK
中科院分区:
医学3区
文献类型:
--
作者:
Flores, G;Alquicer, G;Srivastava, LK

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大鼠新生儿海马腹侧(nVH)病变导致成年后出现许多与精神分裂症类似的行为和认知异常,包括对压力和精神兴奋剂的高反应性以及工作记忆、感觉运动门控和社会互动的缺陷。nvh损伤动物的前额皮质(PFC)和伏隔核(NAcc)的分子和神经化学变化表明这些结构在新生儿病变后发生了发育重组。为了确定nVH病变是否导致神经元形态学改变,我们研究了nVH病变对PFC锥体神经元和NAcc中棘神经元树突结构和脊柱密度的影响。在出生后第7天对Sprague-Dawley幼崽进行双侧伊博素酸诱导的VH病变(P7);P70时,采用改良高尔基-考克斯染色法测定神经元形态。结果表明,nVH损伤大鼠第3层锥体神经元基底树突和分支长度及树突棘密度明显降低。NAcc中棘神经元的树突棘密度下降,但树突长度和树突化没有明显变化。这些数据与在精神分裂症患者PFC中观察到的数据相当,表明VH兴奋性投射的发育丧失可能导致PFC和NAcc神经元可塑性的改变,从而可能导致这些动物的行为改变。(c) 2005年由Elsevier Ltd代表IBRO出版。
Neonatal ventral hippocampal (nVH) lesions in rats result in adult onset of a number of behavioral and cognitive abnormalities analogous to those seen in schizophrenia, including hyperresponsiveness to stress and psychostimulants and deficits in working memory, sensorimotor gating and social interaction. Molecular and neurochemical alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. To determine whether nVH lesions lead to neuronal morphological changes, we investigated the effect of nVH lesion on dendritic structure and spine density of pyramidal neurons of the PFC and medium spiny neurons of the NAcc. Bilateral ibotenic acid-induced lesion of the VH was made in Sprague-Dawley pups at postnatal day 7 (P7); and at P70, neuronal morphology was quantified by modified Golgi-Cox staining. The results show that length of basilar dendrites and branching and the density of dendritic spines on layer 3 pyramidal neurons were significantly decreased in rats with nVH lesions. Medium spiny neurons from the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. The data, comparable to those observed in the PFC of schizophrenic patients, suggest that developmental loss of excitatory projections from the VH may lead to altered neuronal plasticity in the PFC and the NAcc that may contribute to the behavioral changes in these animals. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.