The lectin from Schinus terebinthifolia leaf (SteLL) reduces immobility of mice on the tail suspension test dependent on the monoaminergic and nitric oxide signaling.

Depression underlies a common psychiatric disorder that has been rising in the diagnosis of long-term disabilities worldwide. Natural products have been studied as an antidepressant and anxiolytic agents aiming to make available new options for the daily basis treatment of those psychological disorders. SteLL is a lectin extracted from Schinus terebinthifolia leaf that has been revealed as an antimicrobial, immunomodulatory, antitumor, and antinociceptive agent. Nonetheless, the efficacy of SteLL in the treatment of depression has not yet been explored. In view of this, the aim of this study was to investigate the effect of SteLL in an acute protocol for symptoms of depression using the tail suspension test (TST) to assess despair. Administration of SteLL (1, 2 e 4 mg/kg) significantly diminished the immobility time of animals in the TST and this anti-immobility action was dependent on the carbohydrate-recognizing domain (CRD) since the prior incubation with casein (an inhibitor of SteLL carbohydrate-binding property) blocked the effect. SteLL effect was also reversed by pre-treatment with pharmacological antagonists of α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and D1 dopamine receptor as well as by a selective inhibitor of iNOS (aminoguanidine). l-arginine, a precursor of NO, potentiated SteLL anti-immobility effect. In a subacute evaluation, the anti-immobility effect of SteLL persisted after seven days of treatment. Our findings suggest a role of SteLL in the modulation of depression mostly through monoaminergic and nitric oxide signaling.

Unveiling the pathogenesis of perineural invasion from the perspective of neuroactive molecules.

Perineural invasion (PNI) is characterized by an encounter between the cancer cells and neuronal fibers and holds an extremely poor prognosis for malignant tumors. The exact molecular mechanism behind PNI yet remains to be explored. However, it is worth-noting that an involvement of the neuroactive molecules plays a major part in this process. A complex signaling network comprising the interplay between immunological cascades and neurogenic molecules such as tumor-derived neurotrophins, neuromodulators, and growth factors constitutes an active microenvironment for PNI associated with malignancy. The present review aims at discussing the following points in relation to PNI: a) Communication between PNI and neuroplasticity mechanisms can explain the pathophysiology of poor, short and long-term outcomes in cancer patients; b) Neuroactive molecules can significantly alter the neurons and cancer cells so as to sustain PNI progression; c) Finally, careful manipulation of neurogenic pathways and/or their crosstalk with the immunological molecules implicated in PNI could provide a potential breakthrough in cancer therapeutics.

Communication of Glioma cells with neuronal plasticity: What is the underlying mechanism?

There has been a significantly rising discussion on how neuronal plasticity communicates with the glioma growth and invasion. This literature review aims to determine which neurotransmitters, ion channels and signaling pathways are involved in this context, how information is transferred from synaptic sites to the glioma cells and how glioma cells apply established mechanics of synaptic plasticity for their own increment. This work is a compilation of some outstanding findings related to the influence of the glutamate, calcium, potassium, chloride and sodium channels and other important brain plasticity molecules over the glioma progression. These topics also include the relevant molecular signaling data which could prove to be helpful for an effective clinical management of brain tumors in the future.

Synaptic GluN2B/CaMKII-α Signaling Induces Synapto-Nuclear Transport of ERK and Jacob.

A central pathway in synaptic plasticity couples N-Methyl-D-Aspartate-receptor (NMDAR)-signaling to the activation of extracellular signal-regulated kinases (ERKs) cascade. ERK-dependency has been demonstrated for several forms of synaptic plasticity as well as learning and memory and includes local synaptic processes but also long-distance signaling to the nucleus. It is, however, controversial how NMDAR signals are connected to ERK activation in dendritic spines and nuclear import of ERK. The synapto-nuclear messenger Jacob couples NMDAR-dependent Ca(2+)-signaling to CREB-mediated gene expression. Protein transport of Jacob from synapse to nucleus essentially requires activation of GluN2B-containing NMDARs. Subsequent phosphorylation and binding of ERK1/2 to and ERK-dependent phosphorylation of serine 180 in Jacob encodes synaptic but not extrasynaptic NMDAR activation. In this study we show that stimulation of synaptic NMDAR in hippocampal primary neurons and induction of long-term potentiation (LTP) in acute slices results in GluN2B-dependent activation of CaMKII-α and subsequent nuclear import of active ERK and serine 180 phosphorylated Jacob. On the contrary, no evidence was found that either GluN2A-containing NMDAR or RasGRF2 are upstream of ERK activation and nuclear import of Jacob and ERK.