Probes for INS

In 2017, the World Health Organization (WHO) confirmed a new entity, Epstein Barr virus (EBV) + Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS). Traces of EBV transcripts were described in lymphomas, including DLBCL, that were diagnosed as EBV negative by conventional methods. The aim of this study was to detect viral genome by qPCR, as well as LMP1 and EBNA2 transcripts, with a more sensitive method in DLBCL cases from Argentina. Fourteen cases originally considered as EBV negative expressed LMP1 and/or EBNA2 transcripts. In addition, LMP1 and/or EBNA2 transcripts were also observed in bystander cells. However, EBERs+ cells cases by conventional ISH showed higher numbers of cells with LMP1 transcripts and LMP1 protein. In the cases that were EBERS- in tumor cells but with expression of LMP1 and/or EBNA2 transcripts, the viral load was below the limit of detection. This study provides further evidence that EBV could be detected in tumor cells by more sensitive methods. However, higher expression of the most important oncogenic protein, LMP1, as well as increased viral load, are only observed in cases with EBERs+ cells by conventional ISH, suggesting that traces of EBV might not display a key role in DLBCL pathogenesis.

The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb1 receptors (Cb1Rs), Cb2 receptors (Cb2Rs) in the brain have started to attract considerable interest in recent years. With indisputable evidence showing the wide-distribution of Cb2Rs in the brain of different species, they are no longer considered just peripheral receptors. However, in contrast to Cb1Rs, the functionality of central Cb2Rs remains largely unexplored. Here we review recent studies on hippocampal Cb2Rs. While conflicting results about their function have been reported, we have made significant progress in understanding the involvement of Cb2Rs in modulating cellular properties and network excitability. Moreover, Cb2Rs have been shown to be expressed in different subregions of the hippocampus, challenging our prior understanding of the endocannabinoid system. Although more insight into their functional roles is necessary, we propose that targeting hippocampal Cb2Rs may offer novel therapies for diseases related to memory and adult neurogenesis deficits.

Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti-inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds.

Cocaine use disorder (CUD) is a significant public health issue that generates substantial personal, familial, and economic burdens. Still, there are no FDA-approved pharmacotherapies for CUD. Cocaine-dependent individuals report anxiety during withdrawal, and alleviation of anxiety and other negative affective states may be critical for maintaining drug abstinence. However, the neurobiological mechanisms underlying abstinence-related anxiety in humans or anxiety-like behavior in rodents are not fully understood. This review summarizes investigations regarding anxiety-like behavior in mice and rats undergoing cocaine abstinence, as assessed using four of the most common anxiety-related assays: the elevated plus (or its derivative, the elevated zero) maze, open field test, light-dark transition test, and defensive burying task. We first summarize available evidence that cocaine abstinence generates anxiety-like behavior that persists throughout protracted abstinence. Then, we examine investigations concerning neuropeptide, neurotransmitter, and neuromodulator systems in cocaine abstinence-induced anxiety-like behavior. Throughout, we discuss how differences in sex, rodent strain, cocaine dose and dosing strategy, and abstinence duration interact to generate anxiety-like behavior.

Cumulative evidence has pointed out cannabinoid CB2 receptors (CB2r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB2r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: “Receptor, Cannabinoid, CB2” AND “Alcohol-Related Disorders” AND “human/or patients”; “Receptor, Cannabinoid, CB2” AND “Alcohol” OR “Ethanol” AND “rodents/or mice/or rats”. Pharmacological approaches demonstrated that the activation or blockade of CB2r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB2r in brain areas of the reward system. In addition, mice lacking CB2r (CB2KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CNR2 alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CNR2 and an increased risk for developing AUD. This review provides evidence that CB2r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB2r ligands may prove useful for the treatment of AUD in humans.