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The article informs that High-grade glioma represents a challenge for the medical community worldwide. The new World Health Organization classification tried to explain the biological behavior of these tumors, analyzing their metabolic and genetic pathways. The anatomical factors like neuronal and glial subtypes, lateralized gene-expression, spatiotemporal committed stem cells and extracellular composition explain the biological diversity of gliomas and predict their invasiveness.

The article offers information on micro environmental changes and immune escape during the glioblastoma time course. Topics include information on Glioblastoma multiforme (GBM) which is the most prevalent and malignant primary brain tumor; heterogeneous clinical presentation, parenchymal diffusion, and tumor-host interactions; and immune escaping strategies of glioma cells.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1 protein. In the present study, we used a conditional transgenic mouse model of SCA1 to investigate very early molecular and morphological changes related to the behavioral phenotype. In mice with neural deficits detected by rotarod performance, and simultaneous spatial impairments in exploratory activity and uncoordinated gait, we observed both significant altered expression and patchy distribution of excitatory amino acids transporter 1. The molecular changes observed in astroglial compartments correlate with changes in synapse morphology; synapses have a dramatic reduction of the synaptic area external to the postsynaptic density. By contrast, Purkinje cells demonstrate preserved structure. In addition, severe reactive astrocytosis matches changes in the glial glutamate transporter and synapse morphology. We propose these morpho-molecular changes are the cause of altered synaptic transmission, which, in turn, determines the onset of the neurological symptoms by altering the synaptic transmission in the cerebellar cortex of transgenic animals. This model might be suitable for testing drugs that target activated glial cells in order to reduce CNS inflammation. [ABSTRACT FROM PUBLISHER]

Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region.Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 µM. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide. [ABSTRACT FROM AUTHOR]

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The article discusses a study conducted to characterize the time-related changes in the Glioblastoma multiforme (GBM) landscape, using a syngeneic mouse model of primary GBM. It is noted that the proliferating elements triggered astrocyte activation surrounding the GBM cells. The study emphasized the role of functional changes in the microenvironment during the GBM progression.

Changes in corticospinal excitability have been well documented in the preparatory period before movement, however their mechanisms and physiological role have not been entirely elucidated. We aimed to investigate the functional changes of excitatory corticospinal circuits during a reaction time (RT) motor task (thumb abduction) in healthy subjects (HS). 26 HS received single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). After a visual go signal, we calculated RT and delivered TMS at three intervals (50, 100, 150 ms) within RT and before movement onset, recording motor evoked potentials (MEP) from the abductor pollicis brevis (APB) and the task-irrelevant abductor digiti minimi (ADM). We found that TMS increased MEPAPB amplitude when delivered at 150, 100 and 50 ms before movement onset, demonstrating the occurrence of premovement facilitation (PMF). MEP increase was greater at the shorter interval (MEP50) and restricted to APB (no significant effects were detected recording from ADM). We also reported time-dependent changes of the RT and a TMS side-dependent effect on MEP amplitude (greater on the dominant side). In conclusion, we here report changes of RT and side-dependent, selective and facilitatory effects on the MEPAPB amplitude when TMS is delivered before movement onset (PMF), supporting the role of excitatory corticospinal mechanisms at the basis of the selective PMF of the target muscle during the RT protocol. This work was supported by grants from the Italian Minister of University and Research (MUR) (PRIN2017-2017XJ38A4_003-to GC and 5-year special funding (https://www.miur.gov. it/dipartimenti-di-eccellenza) to MB and MT). [ABSTRACT FROM AUTHOR]

How the network around ROS protects against oxidative stress and Parkinson's disease (PD), and how processes at the minutes timescale cause disease and aging after decades, remains enigmatic. Challenging whether the ROS network is as complex as it seems, we built a fairly comprehensive version thereof which we disentangled into a hierarchy of only five simpler subnetworks each delivering one type of robustness. The comprehensive dynamic model described in vitro data sets from two independent laboratories. Notwithstanding its five-fold robustness, it exhibited a relatively sudden breakdown, after some 80 years of virtually steady performance: it predicted aging. PD-related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the collapse, while antioxidants or caffeine retarded it. Introducing a new concept (aging-time-control coefficient), we found that as many as 25 out of 57 molecular processes controlled aging. We identified new targets for "life-extending interventions": mitochondrial synthesis, KEAP1 degradation, and p62 metabolism. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients' prognosis and correct surgical/radiotherapy planning. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BoNT), a presynaptic inhibitor of acetylcholine (Ach) release at the neuromuscular junction (NMJ), is a successful and safe drug for the treatment of several neurological disorders. However, a wide and recent literature review has demonstrated that BoNT exerts its effects not only at the "periphery" but also within the central nervous system (CNS). Studies from animal models, in fact, have shown a retrograde transport to the CNS, thus modulating synaptic function. The increasing number of articles reporting efficacy of BoNT on chronic neuropathic pain (CNP), a complex disease of the CNS, demonstrates that the central mechanisms of BoNT are far from being completely elucidated. In this new light, BoNT might interfere with the activity of spinal, brain stem, and cortical circuitry, modulating excitability and the functional organization of CNS in healthy conditions. Botulinum toxins efficacy on CNP is the result of a wide and complex action on many and diverse mechanisms at the basis of the maladaptive plasticity, the core of the pathogenesis of CNP. This systematic review aims to discuss in detail the BoNT's mechanisms and effects on peripheral and central neuroplasticity, at the basis for the clinical efficacy in CNP syndromes. [ABSTRACT FROM AUTHOR]

Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time‐lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration. Then, we reconstructed the dynamic fusion–fission–mitophagy cycling of mitochondria in a computer model, integrating these processes into a single network mechanism. Both the computational model and the simulations are able to reproduce the proposed mechanism in terms of mitochondrial dynamics, levels of reactive oxygen species (ROS), mitophagy, and mitochondrial quality, thus providing a computational tool for the interpretation of the experimental data and for future studies aiming to detail further the action of NGF on mitochondrial processes. We also show that changes in these mitochondrial processes are intertwined with a metabolic function of NGF in differentiation: NGF directs a profound metabolic rearrangement involving glycolysis, TCA cycle, and the pentose phosphate pathway, altering the redox balance. This metabolic rewiring may ensure: (a) supply of both energy and building blocks for the anabolic processes needed for morphological reorganization, as well as (b) redox homeostasis. [ABSTRACT FROM AUTHOR]