Dalla presenza al remoto: i progetti di PCTO (ex Alternanza Scuola Lavoro) dell'Ufficio Orientamento e URP dell'Area Campus Di Cesena e Forlì

Questo è il racconto del passaggio dalla presenza al remoto nella progettazione dei PCTO (ex Alternanza Scuola Lavoro) dell'Ufficio Orientamento e URP dell'Area Campus Cesena Forlì (Alma Mater Studiorum - Università di Bologna). Il fine è quello di condividere le strategie e attività elaborate per riuscire a mantenere vivi gli obiettivi dei PCTO nonostante la proposta delle attività da remoto, condividendo il nostro lavoro con tutti coloro che lo possano ritenere utile

Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice

Early life experiences that affect the attachment bond formation can alter developmental trajectories and result in pathological outcomes in a sex-related manner. However, the molecular basis of sex differences is quite unknown. The dopaminergic system originating from the ventral tegmental area has been proposed to be a key mediator of this process.Here we exploited a murine model of early adversity (Repeated Cross Fostering, RCF) to test how interfering with the attachment bond formation affects the VTA-related functions in a sex-specific manner.Through a comprehensive behavioral screening, within the NiH RDoC framework, and by next-generation RNA-Seq experiments, we analyzed the long-lasting effect of RCF on behavioral and transcriptional profiles related to the VTA, across two different inbred strains of mouse in both sexes.We found that RCF impacted to an extremely greater extent VTA-related behaviors in females than in males and this result mirrored the transcriptional alterations in the VTA that were almost exclusively observed in females. The sexual dimorphism was conserved across two different inbred strains in spite of their divergent long lasting consequences of RCF exposure.Our data suggest that to be female primes a sub-set of genes to respond to early environmental perturbations.This is, to the best of our knowledge, the first evidence of an almost exclusive effect of early life experiences on females, thus mirroring the extremely stronger impact of precocious aversive events reported in clinical studies in women

第792回 千葉医学会例会・第二内科例会 35.

Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed

Effects of acute ethanol exposure on class I HDACs family enzymes in wild-type and BDNF(+/-) mice

Alterations of brain-derived neurotrophic factor (BDNF) have been associated with the development of addiction to different drugs of abuse, including ethanol (EtOH). EtOH exposure activates the BDNF-signaling cascade in dorsal striatum, which in turn affects further EtOH intake. Different alcohol exposures have been widely demonstrated to modulate chromatin remodeling, affecting histone acetylation/deacetylation balance. Recently, class I histone deacetylases (HDACs) inhibition has been reported to modulate BDNF mRNA expression and to attenuate morphological and behavioral phenomena related to EtOH exposure. However, the role played by different HDAC isoforms in EtOH-induced plasticity is still unclear

Antimicrobial activity against Helicobacter pylori strains and antioxidant properties of blackberry leaves (Rubus ulmifolius) and isolated compounds

8noRubus spp. (Rosaceae) provide extracts used in traditional medicine as antimicrobial, anticonvulsant, muscle relaxant and radical scavenging agents. Resistance to antibiotics used to treat Helicobacter pylori infection as well as their poor availability in developing countries prompted us to test the antimicrobial activity of Rubus ulmifolius leaves and isolated polyphenols against two H. pylori strains with different virulence (CagA+ strain 10K and CagA(-) strain G21). The antioxidant activity (TEAC values) of the tested compounds ranged from 4.88 (gallic acid) to 1.60 (kaempferol), whilst the leaf extract gave a value of 0.12. All the isolated polyphenols as well as the leaf extract showed antibacterial activity against both of the H. pylori strains. The minimum bactericidal concentrations (MBCs) of the extract for H. pylori strains G21 and 10K, respectively, were 1200 microg/mL and 1500 microg/mL after 24h of exposure and 134 microg/mL and 270 microg/mL after 48 h exposure. Ellagic acid showed very low MBC values towards both of the H. pylori strains after 48 h (2 microg/mL and 10 microg/mL for strains G21 and 10K, respectively) and kaempferol toward G21 strain (MBC=6 microg/mL). A relationship between antimicrobial activity and antioxidant capacity was found only for H. pylori strain G21 CagA(-) strain.reservedmixedMartini, Silvia; D'Addario, C.; Colacevich, Andrea; Focardi, Silvia; Borghini, Francesca; Santucci, Annalisa; Figura, Natale; Rossi, ClaudioMartini, Silvia; D'Addario, C.; Colacevich, Andrea; Focardi, Silvia; Borghini, Francesca; Santucci, Annalisa; Figura, Natale; Rossi, Claudi

Long-term depression of striatal DA release induced by mGluRs via sustained hyperactivity of local cholinergic interneurons

: The cellular mechanisms regulating dopamine (DA) release in the striatum have attracted much interest in recent years. By in vitro amperometric recordings in mouse striatal slices, we show that a brief (5 min) exposure to the metabotropic glutamate receptor agonist DHPG (50 μM) induces a profound depression of synaptic DA release, lasting over 1 h from DHPG washout. This long-term depression is sensitive to glycine, which preferentially inhibits local cholinergic interneurons, as well as to drugs acting on nicotinic acetylcholine receptors and to the pharmacological depletion of released acetylcholine. The same DHPG treatment induces a parallel long-lasting enhancement in the tonic firing of presumed striatal cholinergic interneurons, measured with multi-electrode array recordings. When DHPG is bilaterally infused in vivo in the mouse striatum, treated mice display an anxiety-like behavior. Our results demonstrate that metabotropic glutamate receptors stimulation gives rise to a prolonged depression of the striatal dopaminergic transmission, through a sustained enhancement of released acetylcholine, due to the parallel long-lasting potentiation of striatal cholinergic interneurons firing. This plastic interplay between dopamine, acetylcholine, and glutamate in the dorsal striatum may be involved in anxiety-like behavior typical of several neuropsychiatric disorders

Down-regulation of serotonin and dopamine transporter genes in individual rats expressing a gambling-prone profile. A possible role for epigenetic mechanisms

Abstract—Gambling Disorder (GD) is characterized by excessive gambling despite adverse consequences on individual functioning. In spite of some positive findings, it is difficult to draw any conclusion on the genetics of GD. Indeed, beyond DNA sequence variation, other regulatory mechanisms (like those that engage epigenetics) may explain gene alterations in this addictive disease. Wistar male rats underwent an operant task for the evaluation of individual propensity to gamble. Few rats, after having learnt to prefer nose-poking for a large over a small food reward, were sacrificed to obtain a baseline profile of gene expression at both central and peripheral levels. In the remaining rats, probability of occurrence of large-reward delivery decreased progressively to very low levels. Thus, rats were faced with temptation to ‘‘gamble”, i.e. to nosepokefor a binge reward, whose delivery was omitted the majority of times. After 3 weeks of testing, rats showing a clear-cut profile of either gambling proneness or aversion were selected and sacrificed after the last session. A selective down-regulation of i) serotonin transporter in prefrontal cortex, ii) tyrosine hydroxylase in ventral striatum, iii) dopamine transporter in lymphocytes was evidenced in ‘‘gambler” vs ‘‘non-gambler” rats. The exposure to such operant task (compared to home-cage alone) modulated ventrostriatal but not prefrontal genes. A consistent increase of DNA methylation, in one specific CpG site at serotonin transporter gene, was evident in prefrontal cortex of ‘‘gambler” rats. Elucidation of epigenetic changes occurring during GD progression may pave the way to the development of new therapeutic strategies through specific modulation of epigenetic factors

Dynorphin/KOP and nociceptin/NOP gene expression and epigenetic changes by cocaine in rat striatum and nucleus accumbens

Cocaine induces neurochemical changes of endogenous prodynorphin-kappa opioid receptor (pDYN-KOP) and pronociceptin/orphaninFQ-nociceptin receptor (pN/OFQ-NOP) systems. Both systems play an important role in rewarding mechanisms and addictive stimulus processing by modulating drug-induced dopaminergic activation in the mesocortico-limbic brain areas. They are also involved in regulating stress mechanisms related to addiction. The aim of this study was to investigate possible changes of gene expression of the dynorphinergic and nociceptinergic system components in the nucleus accumbens (NA) and in medial and lateral caudate putamen (mCPu and lCPu, respectively) of rats, following chronic subcutaneous infusion of cocaine. In addition, the epigenetic histone modifications H3K4me3 and H3K27me3 (an activating and a repressive marker, respectively) at the promoter level of the pDYN, KOP, pN/OFQ and NOP genes were investigated. Results showed that cocaine induced pDYN gene expression up-regulation in the NA and lCPu, and its down-regulation in the mCPu, whereas KOP mRNA levels were unchanged. Moreover, cocaine exposure decreased pN/OFQ gene expression in the NA and lCPu, while NOP mRNA levels appeared significantly increased in the NA and decreased in the lCPu. Specific changes of the H3K4me3 and H3K27me3 levels were found at pDYN, pN/OFQ, and NOP gene promoter, consistent with the observed gene expression alterations. The present findings contribute to better define the role of endogenous pDYN-KOP and pN/OFQ-NOP systems in neuroplasticity mechanisms following chronic cocaine treatment. The epigenetic histone modifications underlying the gene expression changes likely mediate the effects of cocaine on transcriptional regulation of specific gene promoters that result in long-lasting drug-induced plasticity

Morpho-Functional Changes of Nigral Dopamine Neurons in an α-Synuclein Model of Parkinson's Disease

background: the accumulation of α-synuclein (α-syn) fibrils in intraneuronal inclusions called lewy bodies and lewy neurites is a pathological signature of parkinson's disease (PD). Although several aspects linked to α-syn-dependent pathology (concerning its spreading, aggregation, and activation of inflammatory and neurodegenerative processes) have been under intense investigation, less attention has been devoted to the real impact of α-syn overexpression on structural and functional properties of substantia nigra pars compacta (SNpc) dopamine (DA) neurons, particularly at tardive stages of α-syn buildup, despite this has obvious relevance to comprehending mechanisms beyond PD progression. objectives: we aimed to determine the consequences of a prolonged α-syn overexpression on somatodendritic morphology and functions of SNpc DA neurons. methods: we performed immunohistochemistry, stereological DA cell counts, analyses of dendritic arborization, ex vivo patch-clamp recordings, and in vivo DA microdialysis measurements in a 12- to 13-month-old transgenic rat model overexpressing the full-length human α-syn (Snca+/+ ) and age-matched wild-type rats. results: aged Snca+/+ rats have mild loss of SNpc DA neurons and decreased basal DA levels in the SN. residual nigral DA neurons display smaller soma and compromised dendritic arborization and, in parallel, increased firing activity, switch in firing mode, and hyperexcitability associated with hypofunction of fast activating/inactivating voltage-gated K+ channels and Ca2+ - and voltage-activated large conductance K+ channels. these intrinsic currents underlie the repolarization/afterhyperpolarization phase of action potentials, thus affecting neuronal excitability. conclusions: besides clarifying α-syn-induced pathological landmarks, such evidence reveals compensatory functional mechanisms that nigral DA neurons could adopt during PD progression to counteract neurodegeneration. © 2022 the authors. movement disorders published by wiley periodicals LLC on behalf of International parkinson and movement disorder society