Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological condition

Spectral Efficiency of Random Time-Hopping CDMA

Traditionally paired with impulsive communications, Time-Hopping CDMA (TH-CDMA) is a multiple access technique that separates users in time by coding their transmissions into pulses occupying a subset of $N_\mathsf{s}$ chips out of the total $N$ included in a symbol period, in contrast with traditional Direct-Sequence CDMA (DS-CDMA) where $N_\mathsf{s}=N$. This work analyzes TH-CDMA with random spreading, by determining whether peculiar theoretical limits are identifiable, with both optimal and sub-optimal receiver structures, in particular in the archetypal case of sparse spreading, that is, $N_\mathsf{s}=1$. Results indicate that TH-CDMA has a fundamentally different behavior than DS-CDMA, where the crucial role played by energy concentration, typical of time-hopping, directly relates with its intrinsic "uneven" use of degrees of freedom.Comment: 26 pages, 13 figure

Latent Tuberculosis Infection among Healthcare Students and Postgraduates in a Mediterranean Italian Area: What Correlation with Work Exposure?

Background: Tuberculosis screening is part of the standard protocol for evaluating the risk of infection in healthcare workers. The aim of this study was to evaluate the prevalence of latent tuberculosis infection (LTBI) among students attending various healthcare profession degree courses and postgraduate medical courses at the School of Medicine of the University of Palermo, Italy, and assess the possible professional origin of infection. Methods: In total, 2946 students (2082 undergraduates and 864 postgraduates) took part in a screening program for LTBI between January 2014 to April 2019 using the tuberculin skin test (TST). Students with a positive TST result underwent a Quantiferon-TB test (QFT). Results: Among the 2082 undergraduates, 23 (1.1%) had a positiveTST;theresultwasconfirmedwithQFTfor13(0.62%)ofthem. Amongthe864postgraduate students,24(2.78%)hadapositiveTSTandonly18(2.08%)showedapositiveQTF.Latenttuberculosis infectionsweresignificantlymorefrequentamongpostgraduatesthanundergraduates(2.08% > 0.62%, p < 0.0001). There was a higher number of subjects previously vaccinated for TB (18.87% > 0.24%, p < 0.0001), and of vaccinated subjects found positive for TST and QTF (66.67% > 7.69%, p = 0.001) in the postgraduate group. Conclusion: Latent TB is relatively low among medical school students in our geographic area. Nevertheless, this infectious disease must be regarded as a re-emerging biohazard for which preventive strategies are required to limit the risk of infection, especially among exposed workers

Regulation of mRNA transport, localization and translation in the nervous system of mammals (Review).

Post-transcriptional control of mRNA trafficking and metabolism plays a critical role in the actualization and fine tuning of the genetic program of cells, both in development and in differentiated tissues. Cis-acting signals, responsible for post-transcriptional regulation, reside in the RNA message itself, usually in untranslated regions, 5' or 3' to the coding sequence, and are recognized by trans-acting factors: RNA-binding proteins (RBPs) and/or non-coding RNAs (ncRNAs). ncRNAs bind short mRNA sequences usually present in the 3'-untranslated (3'-UTR) region of their target messages. RBPs recognize specific nucleotide sequences and/or secondary/tertiary structures. Most RBPs assemble on mRNA at the moment of transcription and shepherd it to its destination, somehow determining its final fate. Regulation of mRNA localization and metabolism has a particularly important role in the nervous system where local translation of pre-localized mRNAs has been implicated in developing axon and dendrite pathfinding, and in synapse formation. Moreover, activity-dependent mRNA trafficking and local translation may underlie long-lasting changes in synaptic efficacy, responsible for learning and memory. This review focuses on the role of RBPs in neuronal development and plasticity, as well as possible connections between ncRNAs and RBPs

Abdominal acupuncture for non-responding TMD patients: a retrospective observational study in general practice

Background: Pain related to Temporomandibular Disorders (TMD) is severe, negatively affecting patients' quality of life, and often resistant to conventional treatments. Abdominal Acupuncture (AA) is known to be particularly effective for pain, especially chronic and musculoskeletal pain, but it is still poorly studied and never investigated in TMD patients. Objectives: To analyze the efficacy of AA for the treatment of patients with subacute and chronic pain related to TMD and non-responding to previous conventional therapies (occlusal splint, medications, physical therapy). Methods: Twenty-eight patients, 24 F and four M (mean age 49.36 years), were recruited from January 2019-February 2021. All patients underwent AA treatment: two sessions per week for four weeks, for a total of eight sessions. At the beginning of therapy (T0) and at the end of the cycle (T1) the following data were evaluated: maximum mouth opening (MMO); cranio-facial pain related to TMD (verbal numeric scale, VNS); pain interference with normal activities and quality of life of patients (Brief Pain Inventory, BPI); oral functioning (Oral Behavior Checklist, OBC); impression of treatment effectiveness (Patients' Global Impression of Improvement, PGI-I Scale). Statistical comparison of data before and after the AA treatment was performed by Wilcoxon's signed-rank test (significance level p < 0.05). Results: The MMO values were significantly improved after one cycle of AA (p = 0.0002). In addition, TMD-related pain had a statistically significant decline following AA treatment (all p < 0.001). Patients' general activity and quality of life (BPI) were described as improved following a course of AA, with statistically significant values for all aspects considered (all p < 0.05). Conclusion: Abdominal acupuncture resulted in effective treatment of subacute/chronic-resistant pain related to TMD, capable of improving mandibular function and facial pain, and reduced the interference of pain affecting patients' quality of life

Fundamental Limits of Low-Density Spreading NOMA with Fading

Spectral efficiency of low-density spreading non-orthogonal multiple access channels in the presence of fading is derived for linear detection with independent decoding as well as optimum decoding. The large system limit, where both the number of users and number of signal dimensions grow with fixed ratio, called load, is considered. In the case of optimum decoding, it is found that low-density spreading underperforms dense spreading for all loads. Conversely, linear detection is characterized by different behaviors in the underloaded vs. overloaded regimes. In particular, it is shown that spectral efficiency changes smoothly as load increases. However, in the overloaded regime, the spectral efficiency of low- density spreading is higher than that of dense spreading

Genomic and non-genomic mechanisms of action of thyroid hormones and their catabolite 3,5-diiodo-l-thyronine in Mammals

Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their eects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic eects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic eects), THs also have non-genomic eects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic eects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic eects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug

Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions

All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes. In addition, non-canonical histone proteins (also known as histone variants), the synthesis of which is not directly linked with DNA replication, are used to mark specific regions of the genome. Here, we will discuss the role of the H3.3 histone variant, with particular attention to its loading into chromatin in the mammalian nervous system, both in physiological and pathological conditions. Indeed, chromatin modifications that mark cell memory seem to be of special importance for the cells involved in the complex processes of learning and memory

Lactate as a Metabolite and a Regulator in the Central Nervous System

More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood-Brain Barrier

: The blood-brain barrier (BBB) is a fundamental structure that protects the composition of the brain by determining which ions, metabolites, and nutrients are allowed to enter the brain from the blood or to leave it towards the circulation. The BBB is structurally composed of a layer of brain capillary endothelial cells (BCECs) bound to each other through tight junctions (TJs). However, its development as well as maintenance and properties are controlled by the other brain cells that contact the BCECs: pericytes, glial cells, and even neurons themselves. Astrocytes seem, in particular, to have a very important role in determining and controlling most properties of the BBB. Here, we will focus on these latter cells, since the comprehension of their roles in brain physiology has been continuously expanding, even including the ability to participate in neurotransmission and in complex functions such as learning and memory. Accordingly, pathological conditions that alter astrocytic functions can alter the BBB's integrity, thus compromising many brain activities. In this review, we will also refer to different kinds of in vitro BBB models used to study the BBB's properties, evidencing its modifications under pathological conditions