1,721,009 research outputs found
Cannabidiol-enriched Cannabis sativa L. extract modulates inflammatory-induced human peripheral mononuclear cells response
No full textRecent studies propose non-psychotropic Cannabis sativa L. as a candidate drug having a role in the pathogenic mechanisms involved in inflammation [1]. In order to evaluate the biological effect of a chemically standardized extract of C. sativa var. carmagnola dried female inflorescences (CSE) and its main constituents, the purpose of this study was to investigate the modulation of cannabinoid receptors (CBr) and pro-inflammatory cytokines in an acute inflammatory stress in vitro model. CSE was chemically characterized by HPLC-DAD and GC. The CSE biological effect was investigated on human peripheral blood mononuclear cells (PBMC) firstly exposed to the endotoxin LPS (2, 6, 24 hours) in order to evaluate CBr and cytokines regulation. Then, cells were pre-treated with CSE and its main components at the concentration of 1 μg/ml, followed by a 2 hours stimulation with the endotoxin LPS.
CSE was found to contain cannabidiol (CBD) >20%, THC <0.6% and β-caryophyllene as principal sesquiterpene; flavonoids were found only <0.1%. Short term exposure to LPS significantly downregulated CB1r and CB2r gene expression and induced IL-1β, IL-6 and TNF-α release. CBr transcription resulted attenuat by pre-treatment with CSE, and more with CBD. Moreover, the LPS-induced release of the pro-inflammatory cytokine IL-6 was attenuated by CSE and CBD treatment.
C. sativa extract and its main constituent CBD were able to regulate the LPS-induced inflammatory PBMC response through the modulation of CBr expression. These results contribute to support the role of the non-psychotropic cannabis compounds in the management of the inflammatory mechanisms
P.1.04 Expression of histone variants H3.3 and H2a.z in the rat brain: Physiopathological and pharmacological implications
No full textIn the overall context of epigenetic modifications in charge of managing genome plasticity and dynamics [1, 2], the role of nucleosomal loading of histone variants is becoming increasingly captivating. Two replication-independent isoforms of histones H3 and H2A, namely H3.3 and H2A.Z, have caught attention because of their involvement in neuronal plasticity processes, cognitive functions and behavioral outcomes. In fact, their incorporation/eviction in nucleosomes and their turnover in neurons influence chromatin accessibility and therefore transcription. H3.3 enrichment at gene bodies and promoters of genes involved in synaptic plasticity was proved to be positively correlated with their expression, while learning-induced H2A.Z eviction in specific genes promotes gene transcription, intervening in memory consolidation processes. H3.3 is encoded by H3f3a and H3f3b independent genes, generating identical proteins, namely H3.3A and H3.3B. Notably, H3f3b gene, but not H3f3a, was proved responsive to neuronal activating stimuli as well as environmental triggers and stressful procedures [3]. H2A.Z hypervariants H2A.Z.1 and H2A.Z.2, encoded respectively by H2afz and H2afv genes, regulate both basal and stimulus-induced neuronal gene expression of independent gene sets [4]. Starting from this evidence, the purpose of this study was to characterize basal expression levels of all genes encoding for the histones variants above mentioned in rodent hippocampus and prefrontal cortex (PFC), two brain regions closely related to brain plasticity, cognition and behavior. Adult male rats (n=7) were sacrificed, their brains removed and dissected. Total RNA extraction was performed, followed by total RNA reverse transcription and Real Time PCR, where specific forward and reverse primer were used for each gene encoding for H3.3 (H3f3a and H3f3b), H2A.Z (H2afz and H2afv) and endogenous control GAPDH. Statistical analysis was performed by means of one-way ANOVA; p<0.05 was considered as a threshold for statistically significant difference. Molecular analyses revealed that, for both hippocampus and PFC, H3f3a mRNA was more expressed at the steady-state compared to H3f3b (p<0.001), as happens for H2afz mRNA, which displays higher levels than H2afv (p<0.001). Moreover, comparing hippocampal and PFC mRNA levels for each variant, H3f3a and H3f3b expression was increased in the hippocampus with respect to the prefrontal cortex (p<0.001), and a comparable outcome was showed for H2afv (p<0.001) but not for H2afz (p>0.05). Our results suggest that 1) differential basal expression levels of genes encoding for H3.3 and H2A.Z may underlie unique gene responsiveness following different stimuli, as previously hypothesized by others [3,4], and this may be crucial in highly-responsive, pathological- and environment-related tissues like hippocampus and PFC; 2) striking lower steady-state expression of H3f3b and H2afv genes might imply a major sensitivity to neuronal inputs compared to their correspondent counterparts; 3) higher expression levels in the hippocampus with respect to the PFC might underpin brain-region specific expression and function for histone variants and their isoforms. Together, these data clear the way for further studies meant at investigating stimulus-dependent regulation of H3.3 and H2A.Z gene isoforms expression and their putative involvement in the physiopathology of brain and its diseases [5]. References [1] Rigillo, G., Vilella, A., Benatti, C., Schaeffer, L., Brunello, N., Blom, J.M.C., Zoli, M., Tascedda, F., 2018. LPS-induced histone H3 phospho(Ser10)-acetylation(Lys14) regulates neuronal and microglial neuroinflammatory response. Brain Behav Immun. https://doi.org/10.1016/j.bbi.2018.09.019. [2] Ottaviani, E., Accorsi, A., Rigillo, G., Malagoli, D., Blom, J.M., Tascedda, F., 2013. Epigenetic modification in neurons of the mollusc Pomacea canaliculata after immune challenge. Brain Res. 1537, 18–26. [3] Maze, I., Wenderski, W., Noh, K.M., Bagot, R.C., Tzavaras, N., Purushothaman, I., Elsässer, S.J., Guo, Y., Ionete, C., Hurd, Y.L., Tamminga, C.A., Halene, T., Farrelly, L., Soshnev, A.A., Wen, D., Rafii, S., Birtwistle, M.R., Akbarian, S., Buchholz, B.A., Blitzer, R.D., Nestler, E.J., Yuan, Z.F., Garcia, B.A., Shen, L., Molina, H,. Allis, C.D., 2015. Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron, 87(1), 77-94. [4] Dunn, C. J., Sarkar, P., Bailey, E. R., Farris, S., Zhao, M., Ward, J. M., Dudek, S.M., Saha, R. N., 2017. Histone Hypervariants H2A.Z.1 and H2A.Z.2 Play Independent and Context-Specific Roles in Neuronal Activity-Induced Transcription of Arc/Arg3.1 and Other Immediate Early Genes. eNeuro, 4(4), ENEURO.0040–17.2017. http://doi.org/10.1523/ENEURO.0040-17.2017. [5] Benatti, C., Blom, J.M., Rigillo, G., Alboni, S., Zizzi, F., Torta, R., Brunello, N., Tascedda, F., 2016. Disease-Induced Neuroinflammation and Depression. CNS Neurol. Disord. Drug Targets 15, 414–433
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Deciphering the central immunomodulatory effects of a vortioxetine pretreatment on the LPS-induced inflammatory cascade
Full text linkRedefining operant conditioning of escape behaviour in lymnaea stagnalis
Full text linkThe escape behaviour is one of the many behavioural responses that can be operantly conditioned in a stimulus-dependent manner in both vertebrates and invertebrates. By exposing the pond snail Lymnaea stagnalis repeatedly to a negative reinforcement its natural tendency to explore its surroundings can be operantly conditioned in both adult and aged snails. When adult snails were trained with 100 mM of KCl their number of escapes was significantly decreased and the latency to first escape was significantly increased. Our behavioural protocol allowed us to investigate memory acquisition, consolidation, and retrieval in pre-and post-training sessions over different days. From the 3rd day of training the learned response was strengthened: the number of the escapes in the post-test session remained significantly reduced even when animals were presented with distilled water. Moreover, adult snails exposed to the negative reinforcement for at least 4 days started to escape significantly less than the control group also in the pre-test session. This effect became more pronounced in the following days and was accompanied by a significant increase in the latency to first escape at the beginning of the pre-test on day 6 and 7. Aged snails, instead, showed selective deficiencies when operantly conditioned: memory retention appeared only after 7 days, while memory retrieval could not be induced. This redefined paradigm can help unravelling a variety of sophisticated cognitive phenomena in L. stagnalis and could be employed also to study the basis of memory impairment occurring during neuro-aging
Modulation of neuroplasticity-related targets following stress-induced acute escape deficit
No full textUnderstanding resilience is a major challenge to improve current pharmacological therapies aimed at complementing psychological-based approaches of stress-related disorders. In particular, resilience is a multi-factorial construct where the complex network of molecular events that drive the process still needs to be resolved. Here, we exploit the acute escape deficit model, an animal model based on exposure to acute unavoidable stress followed by an escape test, to define vulnerable and resilient phenotypes in rats. Hippocampus and prefrontal cortex (PFC), two of the brain areas most involved in the stress response, were analysed for gene expression at two different time points (3 and 24 h) after the escape test. Total Brain-Derived Neurotrophic Factor (BDNF) was highly responsive in the PFC at 24-h after the escape test, while expression of BDNF transcript IV increased in the hippocampus of resistant animals 3 h post-test. Expression of memory enhancers like Neuronal PAS Domain Protein 4 (Npas4) and Activity-regulated cytoskeleton-associated protein (Arc) decreased in a time- and region-dependent fashion in both behavioural phenotypes. Also, the memory inhibitor Protein Phosphatase 1 (Ppp1ca) was increased in the hippocampus of resilient rats at 3 h post-test. Given the importance of neurotrophic factors and synaptic plasticity-related genes for the development of appropriate coping strategies, our data contribute to an additional step forward in the comprehension of the psychobiology of stress and resiliency
Investigating the interactions between multiple memory stores in the pond snail Lymnaea stagnalis
No full textThe pond snail Lymnaea stagnalis exhibits various forms of associative learning including (1) operant conditioning of aerial respiration where snails are trained not to open their pneumostome in a hypoxic pond water environment using a weak tactile stimulus to their pneumostome as they attempt to open it; and (2) a 24 h-lasting taste-specific learned avoidance known as the Garcia effect utilizing a lipopolysaccharide (LPS) injection just after snails eat a novel food substance (carrot). Typically, lab-inbred snails require two 0.5 h training sessions to form long-term memory (LTM) for operant conditioning of aerial respiration. However, some stressors (e.g., heat shock or predator scent) act as memory enhancers and thus a single 0.5 h training session is sufficient to enhance LTM formation lasting at least 24 h. Here, we found that snails forming a food-aversion LTM following Garcia-effect training exhibited enhanced LTM following operant condition of aerial respiration if trained in the presence of the food substance (carrot) they became averse to. Control experiments led us to conclude that carrot becomes a ‘sickness’ risk signal and acts as a stressor, sufficient to enhance LTM formation for another conditioning procedure
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