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NEUROPHARMACOLOGY

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

Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, Ponte Pietro Bucci, Cosenza, Italy (M.C., M.M., R.A., G.G., T.G., An.C., R.M.F.); and Faculty of Medicin, La Sapienza University of Rome, Rome, Italy (Al.C.)

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_nR) 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_1,3R mRNA expression pattern was reported for both rodents treated with a chronic 3-NP dose as demonstrated by predominantly low H₁R mRNA levels (>50%) in rat striatum and cortex, whereas extremely high H₃R levels (>80%) characterized the lateral and central amygdala nuclei plus the striatum of hamsters. Interestingly, the H₃R antagonist (thioperamide) blocked 3-NP-dependent behaviors plus induced an up-regulation of H₁R 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_1,3R subtypes of amygdalar neurons in this hibernating model.

Address correspondence to: Marcello Canonaco, Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, Ponte P. Bucci, 87030 Arcavacata di Rende, Cosenza, Italy. E-mail: canonaco{at}unical.it

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