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Purpose of the study: We aimed to investigate whether m-calpain (a Ca2+-dependent neutral cysteine protease) is released from synaptosomes.Materials and methods: This research was carry on Wistar m...

In recent years, there has been discussion that essential tremor (ET) might be a neurodegenerative disease. Indicators of inflammation are considered as possible biomarkers of neurodegeneration. In this connection, the aim of our study was to identify the relationship between serum inflammation markers and clinical features in ET, including the severity of tremor, cognitive decline, depression.The serum interleukin-1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were measured in 90 ET patients and 90 healthy control people of the corresponding age and gender. Fahn-Tolosa-Marin scale was used for the severity of the tremor. Cognitive function was assessed using the MoCA. Affective symptoms were measured by the Beck Depression Inventory.ET patients had significantly lower serum TNF-α (Our findings demonstrate that neuroinflammation makes a certain contribution to the development of ET.

Some mechanisms of neuronal degeneration in endotoxinemia are already well described, but need to be detailed. In this study, we tested the effect of a single intraperitoneal injection of a LPS sub-septic dose (1 mg/kg of animal weight) on calpain activity in the striatum and hippocampus. We showed, that in the hippocampus the day after LPS administration an increase in production of IL-1β and TNF-α mRNA, followed by elevated mRNA expression and activity of µ- and m-calpains without signs of microglia activation is observed. In striatal cells, the day after LPS injection an increase in expression of IL-1β, TNF-α, IBA-1, m-calpain and calpastatin mRNA is revealed, which only intensifies over time. The elicited changes are accompanied by a decrease in motor behavior, which can be considered as a sign of sickness behavior. In the hippocampus, 180 days after LPS administration expression of TNF-α, content and activity of µ-calpain are increased. In the striatum, elevation in expression of TNF-α, IBA-1, µ- and m-calpain mRNA, with hyperactivation of only m-calpain, is observed. Significantly reduced motor activity can be a consequence of LPS-induced neuronal death. A long-lasting endotoxin activates microglia that damage neurons via proinflammation cytokines and calpain hyperactivation. The endotoxin hypothesis of neurodegeneration is unproven, but if correct, then neurodegeneration may be reduced by decreasing endotoxin-induced neuroinflammation and m-calpain hyperactivation. Therefore, the drugs, that decrease endotoxin-induced neuroinflammation and differently inhibit µ- or m-calpain, can be used to prevent or reduce the severity of neurodegeneration.

Prolonged exposure to manganese (Mn) may lead to toxic effects on the central nervous system (CNS). The mechanisms underlying neuronal death from exposure to Mn are not well understood but undoubtedly involve inflammatory processes. The aim of this study was to explore the effects of long-lasting intranasal Mn exposure in rats focusing on inflammatory processes and catecholamine (dopamine, norepinephrine) levels in the striatum and hippocampus. It was found that intranasal administration by instillation of MnCl2 solution once a day for 90 days leads to impaired movement and gait. We also observed that Mn concentration increased in the hippocampus (by 30 %) and in the striatum (by 220 %), dopamine (24 %) and DOPAC (35 %) were reduced in the striatum, and dopamine (190 %) and DOPAC (220 %) levels increased with simultaneously norepinephrine reduction (30 %) in the hippocampus. Observation of cytokine mRNA revealed increased expression of both assayed cytokines (IL-1β and TNF-α) in the hippocampus. There was a 3-fold increase in the expression of IBA-1 mRNA, 2-fold increase in NFκB mRNA, and dramatic reduction in IkB mRNA in the striatum. Taken together, intranasal exposure to a high dose of MnCl2 induces neuroinflammation and neurotransmission disturbance, but the effects are specific for each studied brain region.

The main obstacle to the use of many therapeutic peptides in practice is their rapid destruction by extracellular peptidases. Earlier we have found that active in the extracellular medium of mammalian brain exopeptidases are unable to break the bonds formed by β-alanine. We have designed several modified forms of opioid peptide enkephalin (Tyr-Gly-Gly-Phe-Met; Enk) with end βAla: ModEnk1 (βAla-Tyr-Gly-Gly-Phe-Met-βAla), ModEnk2 (βAla-Tyr-Gly-Gly-Phe-NH2), ModEnk3 (βAla-Tyr-Gly-Phe-NH2). These modifications are much more stable than Enk in the suspension of isolated axonal endings (synaptosomes) that mimics the brain extracellular medium. ModEnk1-3 have been tested in standard "pain" experiment "tail flick" on rats using intranasal peptide administration. ModEnk1 and ModEnk2 (but not ModEnk3) have fully preserved pain-relieving properties of Enk, but their efficiency was maintained for much longer. Compared to ModEnk1, ModEnk2 is more stable and provides longer analgesia because it is less accessible for endopeptidases. They are potent non-toxic analgesics.

Review of Prostitution: Herstellungsweisen einer anderen Welt by Martina Low and Renate Ruhne