Basal forebrain magnocellular cholinergic systems are damaged in mice following neonatal hypoxia-ischemia.
Basal forebrain magnocellular cholinergic systems are damaged in mice following neonatal hypoxia-ischemia.
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DOI：
10.1002/cne.25263
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发表时间：
2022-06
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影响因子：
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新生儿缺氧缺血性脑病（HIE）可导致终身神经功能障碍。尽管使用治疗性低温，记忆缺陷和执行功能仍然受到严重影响。从基底前脑到新皮质和海马的胆碱能神经传递是高级皮质功能的中心。我们通过光学显微镜检查了基底前脑，并报告了新生小鼠缺氧缺血（HI）后，出生后40天（P），同侧内侧隔核（MSN）胆碱乙酰转移酶阳性（ChAT）+神经元的丢失。在同侧Meynert基底核（nbM）和纹状体中没有ChAT+神经元的丢失。同侧纹状体和nbM ChAT+神经元异常，ChAT，萎缩和圆齿状体，和畸形出现树突的免疫反应性改变。使用具有3D重建的共聚焦图像，HI小鼠中的nbM ChAT+树突短于假手术（p=0.0001）。MSN中ChAT+神经元的丢失与同侧海马区的丢失直接相关。在nbM和纹状体中，异常ChAT+神经元的百分比分别与同侧大脑皮质和纹状体面积的损失相关。乙酰胆碱酯酶（AChE）活性在相邻的同侧大脑皮层和海马区增加，增加与皮层和海马区的损失呈线性相关。在同侧nbM的大神经元中，组织蛋白酶D+溶酶体的数量和大小增加。新生儿HI后，在整个主要胆碱能系统中发现异常的前脑面积损失的数量。在nbM内也有组织蛋白酶D+颗粒的上调。胆碱能神经病理学可能是新生儿脑损伤后学习、记忆和执行功能永久性障碍的基础。小鼠胆碱能系统：新生儿HIE后表现为执行功能差，记忆力和学习能力下降。我们检查了胆碱能系统，以确定是否有病理可能有助于这些功能的结果。与正常对照组相比，新生儿HI后P10，MSN、nbM和纹状体ChAT神经元的永久性磨损消失，ChAT+神经元呈锯齿状，具有较短的营养不良树突。在nbM中也存在增加和更大的溶酶体。在受损的同侧皮质内，AChE活性异常增加。我们推测新生儿HI后胆碱能系统的永久性损伤是导致这些不良神经功能结局的原因。
Neonatal hypoxic-ischemic encephalopathy (HIE) causes lifelong neurologic disability. Despite the use of therapeutic hypothermia, memory deficits and executive functions remain severely affected. Cholinergic neurotransmission from the basal forebrain to neocortex and hippocampus is central to higher cortical functions. We examined the basal forebrain by light microscopy and report loss of choline acetyltransferase-positive (ChAT)+ neurons, at postnatal day (P) 40, in the ipsilateral medial septal nucleus (MSN) after neonatal hypoxia-ischemia (HI) in mice. There was no loss of ChAT+ neurons in the ipsilateral nucleus basalis of Meynert (nbM) and striatum. Ipsilateral striatal and nbM ChAT+ neurons were abnormal with altered immunoreactivity for ChAT, shrunken and crenated somas, and dysmorphic appearing dendrites. Using confocal images with 3D reconstruction, nbM ChAT+ dendrites in HI mice were shorter than sham (p=0.0001). Loss of ChAT+ neurons in the MSN directly correlated with loss of ipsilateral hippocampal area. In the nbM and striatum, percentage of abnormal ChAT+ neurons correlated with loss of ipsilateral cerebral cortical and striatal area, respectively. Acetylcholinesterase (AChE) activity increased in adjacent ipsilateral cerebral cortex and hippocampus and the increase was linearly related to loss of cortical and hippocampal area. Numbers and size of cathepsin D+ lysosomes increased in large neurons in the ipsilateral nbM. After neonatal HI, abnormalities were found throughout the major cholinergic systems in relationship to amount of forebrain area loss. There was also an upregulation of cathepsin D+ particles within the nbM. Cholinergic neuropathology may underlie the permanent dysfunction in learning, memory, and executive function after neonatal brain injury. Mouse cholinergic systems: Poor executive function and decreases in memory and learning are seen after neonatal HIE. We examined the cholinergic systems to determine if there is pathology there that could contribute to these functional outcomes. In contrast to normal, after neonatal HI on P10, loss of permanent attrition of ChAT neurons in the MSN, nbM and striatum is found. ChAT+ neurons are crenated with shorter dystrophic dendrites. Increased and larger lysosomes are also present in the nbM. Within the injured ipsilateral cortex, AChE activity is abnormally increased. We hypothesize that permanent injury to the cholinergic systems after neonatal HI is responsible for these poor neurologic outcomes.
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影响因子：
3.3
作者：
Ginsberg, SD;Martin, LJ
通讯作者：
Martin, LJ
DOI：
10.1017/s1355617708080053
发表时间：
2008-01-01
影响因子：
2.6
作者：
Edgin, Jamie O.;Inder, Terrie E.;Woodward, Lianne J.
通讯作者：
Woodward, Lianne J.
影响因子：
3.7
作者：
Fayzullina S;Martin LJ
通讯作者：
Martin LJ
影响因子：
6
作者：
Chang, Qing;Martin, Lee J.
通讯作者：
Martin, Lee J.
影响因子：
6.1
作者：
Carloni, Silvia;Buonocore, Giuseppe;Balduini, Walter
通讯作者：
Balduini, Walter