dc.description.abstract | At date, a plethora of evidence regarding adverse morpho-functional and neurobiological
aspects provoked by environmental stressors has been considered. Following exposure to
stress factors, the activation of both specific neurosignaling mechanisms and molecular
pathways account for the modulation of complex adaptative processes in animal targets. In
this context, the aim of the present work is to analyze the neuroprotective role of
histaminergic system and heat shock proteins towards environmental neurotoxicants such as
heavy metals and pesticides in the Teleost Thalassoma pavo. Such environmental stressors
account for significative alterations on motor and feeding behaviors, which are tightly
correlated to neurodegenerative processes in key brain regions. In this work, the molecular
characterization of H2R and H3R permits to demonstrate a conservation of specific
sequences, which appear to be determinant for the function of such subtypes in
phylogenetically distant Vertebrates. Moreover, the inactivation of H2R and H3R, via the
application of selective antagonists (Cimetidine and Thioperamide, respectively), induces in
Thalassoma pavo abnormal behaviors and trascriptional alterations, suggesting a clear
physiological role of this neuronal system in our model. The expression pattern of
histaminergic system results to be highly modified following exposure to environmental
stressors in a region-dependent manner. In particular, the heavy metals induce
downregulations of H2R mRNA in some brain regions such as mesencephalon, which is
involved in the regulation of motor activities. On the other hand, both heavy metal and
pesticides account for an increasement of H3R trascriptional levels in hypothalamic and
telencephalic areas. From the concomitant exposure to histaminergic antagonists and
environmental stressors, it was possible to demonstrate that H2R blockade is responsible for
enhanced stressors-dependent neurotoxic effects. On the contrary, the inhibition of H3R
activities accounts for an amelioration of both abnormal motor behaviors and neuronal
damage induced by such environmental stressors. Consistent with the effects on
histaminergic system, heavy metals and pesticides also promote the activation of cellular
defence processes through the stimulation of heat shock proteins trascription, i.e. HSP90 e
HSP70. The histaminergic antagonists are able to influence heat shock proteins expression,
inducing a heterogeneous pattern of HSP90 trascription levels, while in the case of HSP70
an enhanced expression is typical of all encephalic areas. The results of the present work
demonstrate, for the first time in an aquatic Vertebrate, a possible interactions between
histaminergic system-dependent neurosignaling activities and HSPs network, which could be
represent an important neurophysiological mechanism operating during neuronal stress
conditions. | en_US |