The Histaminergic Signaling System Exerts a Neuroprotective Role against Neurodegenerative-Induced Processes in the Hamster

Abstract

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 (Ͼ50%) in rat striatum and cortex, whereas extremely high H 3 R levels (Ͼ80%) 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 H 1,3 R subtypes of amygdalar neurons in this hibernating model.

A sexually dimorphic distribution pattern of the novel estrogen receptor G-protein-coupled receptor 30 in some brain areas of the hamster

“…In addition, this pattern was correlated to that of both ERa and ERb as well as ERK1/2 considering the protective roles exerted by these factors against excitotoxicity events in cortical and hippocampal neurons (Nilsen & Diaz 2003). Overall, the resulting sexually dimorphic distribution pattern of GPR30 expressing neurons could nicely represent a starting point regarding its role not only on estrogen functions in the absence of ERs, but also on ischemic-like events that are evoked in hibernators during arousal (Canonaco et al 2005).…”

“…This feature is sustained by the expression of GPR30 not only in ER-enriched areas and so tends to further corroborate its critical role in the estrogen actions above all in facultative hibernators. Studies in our animal model are only at the beginning and further interests especially during the different hibernating states could prove to be useful for the unveiling of pathological processes such as ischemia that occurs during the arousal phase (Canonaco et al 2005) of this particular physiological condition.…”

Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases

“…thioperamide and ABT-239, have been revealed in in vitro and in vivo kainic acid-or 3-nitropropionic acid (3-NP)-induced neurotoxicity models [113,114]. In a previous study, upregulation of H3Rs down-regulation of H1Rs have been found to coincide with excessive neuronal damage and behavioral effects as a consequence of 3-NP-induced neurotoxicity in hamster and rat [115]. Moreover, another interesting H3R antagonist, namely JNJ-5207852, was found to ameliorate different memory deficits induced by PTZ kindling in weanling mice [116].…”

Influence of membrane surface properties on the growth of neuronal cells isolated from hippocampus

“…We used neurons isolated from hippocampus, which is an important brain area owing to its vital role in the consolidation of several forms of learning and memory and especially during the formation of declarative memories [16,17]. Hippocampal neurons, which are well known for their plasticity and regeneration properties [18], are the best-characterised model for investigating polarization that occurs spontaneously during the first days of culture [19][20][21].…”