Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Clinical and experimental evidence suggest that the activation of the nicotinic acetylcholine receptor (nAChR) could be protective for PD. In this study, we investigated the neuroprotective capacity of nicotine in a rat PD model. Considering that iron metabolism has been implicated in PD pathophysiology and nicotine has been described to chelate this metal, we also studied the effect of nicotine on the cellular labile iron pool (LIP) levels. Rotenone (1 μg) was unilaterally injected into the median forebrain bundle to induce the degeneration of the nigrostriatal pathway. Nicotine administration (1 mg/K, s.c. daily injection, starting 5 days before rotenone and continuing for 30 days) attenuated the dopaminergic cell loss in the SNpc and the degeneration of the dopaminergic terminals provoked by rotenone, as assessed by immunohistochemistry. Furthermore, nicotine partially prevented the reduction on dopamine levels in the striatum and improved the motor deficits, as determined by HPLC-ED and the forelimb use asymmetry test, respectively. Studies in primary mesencephalic cultures showed that pretreatment with nicotine (50 μM) improved the survival of tyrosine hydroxylase-positive neurons after rotenone (20 nM) exposure. Besides, nicotine induced a reduction in the LIP levels assessed by the calcein dequenching method only at the neuroprotective dose. These effects were prevented by addition of the nAChRs antagonist mecamylamine (100 μM). Overall, we demonstrate a neuroprotective effect of nicotine in a model of PD in rats and that a reduction in iron availability could be an underlying mechanism.
The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (InsP6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL “debris” at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium InsP6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.
Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato. Hydatids are bladder-like structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly by mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites and draining lymph nodes in infected humans. These observations raise the question of whether LL materials circulate systemically, and if so how they are dealt with by the hosts. We previously reported that LL mucins are bound by a recombinant version of the lectin receptor Clec4F. In rodents, Clec4F is expressed only in Kupffer cells, the liver macrophages exposed to the vascular space. In this article, we show that Kupffer cells take up LL mucins in vivo in a manner dependent on the mucin glycans and Clec4F. In mice harbouring intraperitoneal infections, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. It seems likely that the composition of the LL was adjusted through evolution so that LL debris were taken up by the major phagocytes of the rodent liver, which is the ancestral infection site for Echinococcus larvae. However, our data reveal that Kupffer cells act as a sink for LL materials even when the parasite grows in sites other than the liver, as it happens in natural E. granulosus infections.
Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato , with E. granulosus sensu stricto being the main infecting species. Hydatids are bladderlike structures that attain large sizes within various internal organs of livestock ungulates and humans.
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