Histamine Receptor Expression, Hippocampal Plasticity and Ammonia in Histidine Decarboxylase Knockout Mice
Histamine Receptor Expression, Hippocampal Plasticity and Ammonia in Histidine Decarboxylase Knockout Mice
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DOI：
10.1007/s10571-011-9730-1
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Sergeeva, Olga A.
中科院分区：
文献类型：
--
作者：
Chepkova, Aisa;Yanovsky, Evgenij;Sergeeva, Olga A.
组胺产生酶组氨酸脱羧酶（HDC）的基因切除导致探索行为和依赖于校园的学习的改变。我们研究了HDC基因敲除小鼠（HDC KO）脑组胺缺乏如何影响海马兴奋性、突触可塑性和组胺受体表达。以下方面无显著变化：基础突触传递，长时程增强（LTP）在Schaffer侧支突触，组胺诱导的短暂变化，在CA 1锥体细胞兴奋性，H1和H2受体mRNA的表达被发现在海马切片从HDC KO小鼠。然而，当与WT小鼠相比时，HDC KO小鼠表现出：1.组胺对LTP的增强作用更强; 2.氨对LTP的损害更强，3.组胺对群体峰值无持久的增强作用，4. H3受体mRNA表达降低; 5. H3受体激动作用对群体峰值的增强作用较小。在下丘脑结节乳头状核（神经元组胺的起源）中的平行测量表明，HDC KO小鼠中H3受体的表达增加，而无组胺的“组胺能”神经元的自发放电及其对H3受体激动剂（R）-α-甲基组胺的反应无任何变化。我们的结论是，神经元组胺的情况下，在海马突触传递和可塑性与H3受体的表达改变的微妙变化的结果。
Genetic ablation of the histamine producing enzyme histidine decarboxylase (HDC) leads to alteration in exploratory behaviour and hippocampus-dependent learning. We investigated how brain histamine deficiency in HDC knockout mice (HDC KO) affects hippocampal excitability, synaptic plasticity, and the expression of histamine receptors. No significant alterations in: basal synaptic transmission, long-term potentiation (LTP) in the Schaffer collateral synapses, histamine-induced transient changes in the CA1 pyramidal cell excitability, and the expression of H1 and H2 receptor mRNAs were found in hippocampal slices from HDC KO mice. However, when compared to WT mice, HDC KO mice demonstrated: 1. a stronger enhancement of LTP by histamine, 2. a stronger impairment of LTP by ammonia, 3. no long-lasting potentiation of population spikes by histamine, 4. a decreased expression of H3 receptor mRNA, and 5. less potentiation of population spikes by H3 receptor agonism. Parallel measurements in the hypothalamic tuberomamillary nucleus, the origin of neuronal histamine, demonstrated an increased expression of H3 receptors in HDC KO mice without any changes in the spontaneous firing of "histaminergic" neurons without histamine and their responses to the H3 receptor agonist (R)-alpha-methylhistamine. We conclude that the absence of neuronal histamine results in subtle changes in hippocampal synaptic transmission and plasticity associated with alteration in the expression of H3 receptors.