The histaminergic signaling system exerts a neuroprotective role against neurodegenerative-induced processes in the hamster

被引:31
作者
Canonaco, M
Madeo, M
Alò, R
Giusi, G
Granata, T
Carelli, A
Canonaco, A
Facciolo, RM
机构
[1] Univ Calabria, Dept Ecol, Comparat Neuroanat Lab, I-87030 Cosenza, Italy
[2] Univ Roma La Sapienza, Fac Med, Rome, Italy
关键词
D O I
10.1124/jpet.105.088153
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The neurotoxic 3-nitropropionic acid (3-NP), a freckled milk vetch-derived inhibitor of mitochondrial enzymatic processes that is capable of mimicking the typical pathological features of neurodegenerative disorders, behaved in a differentiated manner in a hibernating rodent (hamster) with respect to a nonhibernating rodent (rat). Treatment of the two rodents with both an acute and chronic 3-NP dose supplied deleterious neuronal effects due to distinct histamine receptor (H n R) transcriptional activities, especially in the case of the rat. In hamsters, these treatment modalities accounted for overall reduced global activity in a freely moving environment and overt motor symptoms such as hindlimb dystonia and clasping with respect to the greater abnormal motor behaviors in rats. This behavioral difference appeared to be strongly related to qualitative fewer neuronal alterations and, namely, lesser crenated cell membranes, swollen mitochondria, and darkened nuclei in hamster brain areas. Moreover, a mixed H 1,3 R mRNA expression pattern was reported for both rodents treated with a chronic 3-NP dose as demonstrated by predominantly low H 1 R mRNA levels (> 50%) in rat striatum and cortex, whereas extremely high H 3 R levels (> 80%) characterized the lateral and central amygdala nuclei plus the striatum of hamsters. Interestingly, the H 3 R antagonist (thioperamide) blocked 3-NP-dependent behaviors plus induced an up-regulation of H 1 R levels in mainly the above-reported hamster amygdalar nuclei. Overall, these results show, for the first time, that a major protective role against neurodegenerative events appears to be strongly related to the expression activity of H1,3R subtypes of amygdalar neurons in this hibernating model.
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页码:188 / 195
页数:8
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