Pharmacology (medical), Psychiatry and Mental health
299
Scopus Publications
Scopus Publications
Dose-dependent modulation of social and motivational behavior by lurasidone in a rat model of social defeat Eleonora Corridori, Alessia Marchesin, Camilla Amato, Veronica Begni, Sara Salviati, Carla Gambarana, Marco Andrea Riva, Simona Scheggi Progress in Neuro Psychopharmacology and Biological Psychiatry, 2026 Chronic psychosocial stress is a key risk factor for psychiatric disorders, often causing motivational and social impairments poorly responsive to conventional pharmacotherapies. The present study investigated the effects of chronic lurasidone treatment on behavioral and molecular alterations induced by prolonged social defeat (SD) stress in adult male rats. Rats underwent resident-intruder SD paradigm for approximately seven weeks and treated orally with lurasidone (1 or 3 mg/kg/day) during the final three weeks. Motivational drive was assessed using sucrose self-administration under fixed and progressive ratio schedules, while sociability was evaluated through social interaction tests. Molecular analysis quantified DARPP-32 dopaminergic response to social stimuli and gene expression [immediate early genes (Arc, c-Fos, Npas4, Zif268) and glucocorticoid-responsive genes (Sgk1, Fkbp5, Dusp1, Nr4a1)] across corticolimbic regions, including the nucleus accumbens and prefrontal cortex. SD stress caused anhedonia and social withdrawal. Treatment with lurasidone at 3 mg/kg, but not 1 mg/kg, effectively restored motivational performance, as indicated by normalized breaking points in the progressive ratio task. Both doses ameliorated the stress-induced social deficits, and DARPP-32 responses, although with different magnitudes. At the molecular level, SD disrupted activity-dependent and glucocorticoid-responsive transcription and functional coupling between brain regions. Lurasidone reinstated coordinated network activation, particularly during social stimulation, suggesting a dose- and context-dependent facilitation of neuronal plasticity. Overall, chronic lurasidone treatment counteracts stress-induced impairments in motivation and sociability through the restoration of corticolimbic network activity. Such effects may underlie its clinical efficacy in addressing negative and motivational symptoms across affective and psychotic disorders.
Sex-dependent protective effects of a ketogenic diet following prenatal stress exposure: Evidence from adolescent rats Veronica Begni, Alessia Marchesin, Rodrigo Orso, Kerstin Camile Creutzberg, Federica Precetti, Annamaria Cattaneo, Marco Andrea Riva Brain Behavior and Immunity, 2026 • Post-weaning ketogenic diet rescues prenatal-stress-induced sociability deficits. • KD lowers ’vulnerable’ PNS offspring from ∼50 % to 22 % (males) and 12 % (females). • KD modulates PFC E/I markers: increased PV/SST in males; PSD95 restored in females. • Ketosis (increased concentration of β-hydroxybutyrate) lowers PFC neuroinflammation (TNFα, IL-6, C4). • Sex-dependent KD effects on NRF2/KEAP1 redox signalling in PFC. Exposure to stress during gestation (prenatal stress, PNS) disrupts neurodevelopmental trajectories and increases vulnerability to neuropsychiatric disorders, through dysregulation of different molecular pathways. PNS-induced alterations frequently emerge during adolescence, a highly dynamic maturational period, highlighting a critical window in which therapeutic interventions may modify pathological outcomes. Here, we investigated whether a post-weaning ketogenic diet (KD) could modulate PNS-induced behavioral and molecular alterations in adolescent Sprague–Dawley rats. At weaning offspring from dams exposed to repeated restraint stress during gestation were assigned to a control diet (CD) or KD. Behavioral testing was conducted during adolescence, and prefrontal cortex (PFC) was analyzed for excitatory/inhibitory markers, redox regulators, and inflammatory mediators. PNS induced sociability deficits that were ameliorated by KD. A two-step cluster analysis identified ∼50–55 % of PNS offspring as “vulnerable,” whereas KD reduced this proportion to 22 % in males and 12 % in females. At the molecular level, KD exerted sex-dependent effects in the PFC: in males, it enhanced inhibitory interneuron markers and reduced pro-inflammatory transcripts while altering NRF2/KEAP1 redox signaling; in females, it increased NRF2 and partially restored GCLC1, while PNS selectively disrupted inhibitory and excitatory markers. Together, these findings demonstrate that post-weaning KD rescues PNS-induced social deficits and reshapes PFC molecular profiles, engaging sex-specific mechanisms of resilience. In summary, diet-based interventions during adolescence may represent a promising strategy to counteract developmental stress-related vulnerability.
Distinct Molecular Responses to Ketamine and Imipramine in Cortical and Striatal Regions Following Acute Swim Stress Veronica Begni, Floriana De Cillis, Natascha Pfeiffer, Steven Roger Talbot, Peter Gass, Annamaria Cattaneo, Marco Andrea Riva, Anne Stephanie Mallien Biomolecules, 2026 Pharmacological antidepressant treatments alter the molecular and functional reactivity of stress-sensitive neural networks. However, how classical versus rapid-acting antidepressants differentially modulate acute stress-induced transcriptional responses across brain regions remains unclear. Here, we compared imipramine and ketamine in mice exposed to acute swim stress, assessing transcriptional adaptations across the frontal cortex, hippocampus, and striatum. Swim stress induced significant widespread activation of cFOS, which led to drug-specific modulations: imipramine primarily significantly dampened cortical and striatal cFOS expression, whereas ketamine preserved stress-evoked neuronal activation. In contrast, hippocampal activation was significantly robust but largely unaffected, indicating that acute antidepressant drug effects during stress coping preferentially target cortical and striatal plasticity mechanisms. In contrast, BDNF expression was altered only within the striatal region, where imipramine attenuated the stress-related increase in BDNF expression. Statistical analysis of behavioral outcomes during the swim stress confirmed a shared facilitation of active coping, yet these similar outcomes emerged from distinct molecular programs. Together, the data demonstrate that the treatment effects of the two substances diverge mechanistically, revealing cortical and striatal transcriptional signatures of classical versus rapid-acting antidepressant action. While these findings suggest potential translational relevance for understanding distinct mechanisms, further studies in humans are required to validate these signatures and their clinical implications.
Lurasidone Sub-Chronic Treatment During Adolescence Modulates Inflammatory and Inositol-Related Metabolic Pathways in the Prefrontal Cortex of Adult Male Rats Exposed to Prenatal Stress Monica Mazzelli, Samantha Saleri, Valentina Zonca, Moira Marizzoni, Marco Andrea Riva, Veronica Begni, Annamaria Cattaneo Biomolecules, 2026 Prenatal stress (PNS) predisposes individuals to mental disorders later in life. Adolescence is a period of heightened brain plasticity and vulnerability, when many mental disorders emerge, yet pharmacological strategies remain largely underexplored. In adult PNS rats, lurasidone (LUR) has been shown to reduce PNS-induced risk; however, its effects following adolescent administration remain unclear. To investigate the long-lasting effects of PNS and their modulation following sub-chronic LUR adolescent treatment, a whole-genome expression analysis of the prefrontal cortex (PFC) of adult male PNS rats was performed. Twelve PNS and eleven control rats were randomly assigned to receive vehicle or LUR from postnatal day (PND) 35 to 49 and sacrificed at PND 50. Partek Genomics Suite and Ingenuity Pathway Analysis were used for differential expression and pathway analyses. Within the PFC, PNS induced an upregulation of pathways involved in environmental information processing and in immune system-related pathways, which was reduced after LUR, as observed by IL-8 signaling (z-scores before: 1.34 and after LUR: −2.65). In parallel, LUR administration itself modulated Inositol-related metabolic pathways. Overall, these findings suggest that LUR adolescent treatment may counteract some PNS-induced alterations, supporting adolescence as a critical window for early preventive strategies with translational relevance for stress-related neuropsychiatric disorders.
A Wide Syndrome Through a Narrow Lens—and One Uniform Pressure Marco Riva, Alfonso Fasano Movement Disorders Clinical Practice, 2026 Ethical Compliance Statement: No institutional review board or ethics committee was requested to approve the current manuscript, at it is a short essay regarding a clinical trial performed elsewhere. No author of the current manuscript was involved in the referred study. Informed patient consent was not necessary for this work. All authors have read and complied with the Journal's Ethical Publication Guidelines. We both confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial Disclosures and Conflicts of Interest: Author disclosures are available in the Supporting Information. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Data S1. Coi_disclosure. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dynamic MRI in Degenerative Cervical Myelopathy: A Systematic Review of Radiological Markers, Correlations, and Outcomes Ali Baram, Jad El Choueiri, Carlo Brembilla, Francesca Pellicanò, Lorenzo De Rossi, Leonardo Di Cosmo, Mario De Robertis, Emanuele Stucchi, Donato Creatura, Gabriele Capo, Maurizio Fornari, Marco Riva, Letterio S. Politi, Federico Pessina Journal of Clinical Medicine, 2026 Background/Objectives: Conventional static magnetic resonance imaging may underestimate the severity of cervical cord compression by failing to account for positional changes in the spinal canal. Dynamic MRI (dMRI) captures cervical motion, allowing evaluation of cord compression under physiological loading. This systematic review aimed to synthesize evidence on how dMRI modifies the assessment of spinal canal narrowing and signal change, and how these findings correlate with impairment and postoperative outcomes in degenerative cervical myelopathy. Methods: A systematic literature search was conducted across PubMed, Scopus, and Embase databases according to PRISMA guidelines. Studies evaluating the role of dMRI (flexion–extension MRI) in diagnosing or predicting outcomes of cervical degenerative pathology were included. Data were extracted on imaging protocols, diagnostic findings, quantitative parameters, and clinical outcomes. Results: Nineteen studies met the inclusion criteria. dMRI consistently revealed motion-dependent stenosis and intramedullary signal changes not visible on static imaging. Extension imaging frequently demonstrated disease progression, showing altered spinal cord area, cerebrospinal fluid (CSF) reserve, and additional compression levels. Dynamic sequences enhanced sensitivity for pathological segment detection and improved correlation with clinical severity. Preoperative dMRI findings, particularly extension-related compression and T2 hyperintensity, predicted postoperative neurological recovery and influenced surgical planning in up to one third of cases. Conclusions: Dynamic MRI provides superior diagnostic sensitivity and prognostic information compared with static imaging by revealing motion-induced spinal cord compression and microstructural alterations. It should be considered when clinical findings exceed static MRI severity or when the symptomatic level is uncertain. Standardization of protocols and large prospective studies are needed to define evidence-based clinical indications.
Inflammatory status along the brain-liver axis in animals vulnerable to prenatal stress: sex-related implications for stress-induced comorbidities Ilari D’Aprile, Giulia Petrillo, Veronica Begni, Kerstin Camile Creutzberg, Rodrigo Orso, Rodrigo Grassi-Oliveira, Marco Andrea Riva, Annamaria Cattaneo Translational Psychiatry, 2025 The prevalence of mood disorders is constantly increasing, with exposure to stress early in life (ELS) as one of the major risk factors. Recent studies reported that ELS can increase the risk for mental disorders, but also for several cardiometabolic conditions, often in comorbidity. However, biological processes underlying these negative outcomes with a sex dependent effect are still poorly understood. Here, we used the preclinical model of prenatal stress (PNS) mimicking early in life adversities to investigate the presence of an abnormal inflammatory response as a possible mechanism leading to the onset of a vulnerable phenotype for mental and metabolic disorders in the offspring. We showed that adolescent male rats, classified as vulnerable to PNS by a two-step cluster analysis, based on three different behavioral tests, have brain microglia hyperactivation in the dorsal hippocampus. We then focused on liver, as a key organ involved in the development of several metabolic disorders and strictly communicating with the brain via immune-inflammatory pathways. We found that rats showing a vulnerable behavioral phenotype also showed abnormal inflammatory response in the liver. Moreover, liver inflammation is correlated with an increased expression of leptin receptor, an important adipokine involved in several metabolic processes. Overall, this study suggests that male but not female rats exposed to PNS and showing a vulnerable phenotype are characterized by brain and liver pro-inflammatory status, pointing out the need to target the inflammatory system via pharmacological or non-pharmacological strategies to reduce the risk for both mental and physical disorders in individuals exposed to ELS.
Sex-dependent preventive effects of prenatal N-acetyl-cysteine on neuronal, emotional and metabolic dysfunctions following exposure to maternal high-fat diet in mice Chiara Musillo, Marianna Samà, Kerstin Camile Creutzberg, Veronica Begni, Barbara Collacchi, Jonida Bitraj, Ginetta Collo, Marco Andrea Riva, Alessandra Berry, Francesca Cirulli Translational Psychiatry, 2025 While a clear association between maternal obesity and an increased risk for neuropsychiatric disorders in the offspring has been described, the underlying mechanisms remain poorly understood. We hypothesised that a maternal high-fat diet (mHFD) would act as a stressor, increasing glucocorticoids, resulting in an altered redox balance and disrupted neuronal plasticity of the limbic system. Such enduring effects would impair the emotional and cognitive profile, neuroendocrine responses, and metabolic and redox homeostasis in the adult offspring. We utilised a mouse model and a translational cellular model employing human neurons derived from inducible Pluripotent Stem Cells (iPSCs) to evaluate the impact of mHFD on neurodevelopment and to test the protection afforded by the antioxidant N-acetyl-cysteine (NAC). Our approach combined behavioural and metabolic phenotyping, biochemical assays, morphological assessment, and targeted gene expression analysis. Results indicate that prenatal administration of NAC prevented anxiety-like and risk-taking behaviours, cognitive impairments and metabolic alterations in mHFD adult mouse offspring, particularly in females. These changes were accompanied by hippocampal downregulation of genes involved in neuronal plasticity, such as BDNF. Using human neurons in vitro, pre-treatment with NAC rescued the negative effects of glucocorticoids on neuronal plasticity via a BDNF-mediated mechanism. The protective effects of NAC over mHFD in females suggest that rebalancing the redox status could be exploited as an overall strategy to buffer the negative effects of early adversities on neurodevelopment.
Extracellular vesicles released by glioblastoma cancer cells drive tumor invasiveness via Connexin-43 gap junctions Matteo Tamborini, Valentino Ribecco, Elisabetta Stanzani, Arianna Sironi, Monica Tambalo, Davide Franzone, Elena Florio, Edoardo Fraviga, Chiara Saulle, Maria C Gagliani, Marco Pizzocri, Milena Mattioli, Katia Cortese, Jean X Jiang, Giuseppe Martano, Letterio S Politi, Marco Riva, Federico Pessina, Davide Pozzi, Simona Lodato, Lorena Passoni, Michela Matteoli Neuro Oncology, 2025
Understanding, predicting, and treating depression in pregnancy to improve mothers' and offspring's mental health outcomes: The HappyMums study A. Biaggi, V. Zonca, C. Anacker, V. Begni, F. Benedetti, A. Bramante, A. Braniecka, V. Brenna, M. Bulgheroni, C. Buss, L. Cavaliere, C.A.M. Cecil, A.C. Couch, D. de Barra, H. El Marroun, S. Entringer, R. Grassi-Oliveira, M. Jackowska, A. Korosi, P.J.C. Kwant, J. Lahti, K. Lekadir, I. Mansuy, F. Manuella, M. Marizzoni, U. Meyer, C. Monk, S. Nakić Radoš, C.M. Pariante, B.J.A. Pollux, K. Priestley, K. Räikkönen, J. Richetto, M.A. Riva, L.M. Rothmann, V. Simonetti, B. Vai, A.C. Vernon, M. Žutić, A. Cattaneo Brain Behavior and Immunity Health, 2025
Drug repositioning for treatment-resistant depression: Hypotheses from a pharmacogenomic study Chiara Fabbri, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Marco Andrea Riva, Cathryn M. Lewis, Alessandro Serretti Progress in Neuro Psychopharmacology and Biological Psychiatry, 2021
Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis Christoph Anacker, Annamaria Cattaneo, Ksenia Musaelyan, Patricia A. Zunszain, Mark Horowitz, Raffaella Molteni, Alessia Luoni, Francesca Calabrese, Katherine Tansey, Massimo Gennarelli, Sandrine Thuret, Jack Price, Rudolf Uher, Marco A. Riva, Carmine M. Pariante Proceedings of the National Academy of Sciences of the United States of America, 2013
Serum and plasma BDNF levels in major depression: A replication study and meta-analyses Luisella Bocchio-Chiavetto, Vincenzo Bagnardi, Roberta Zanardini, Raffaella Molteni, Maria Gabriela Nielsen, Anna Placentino, Caterina Giovannini, Luciana Rillosi, Mariacarla Ventriglia, Marco A. Riva, Massimo Gennarelli World Journal of Biological Psychiatry, 2010
BDNF Val66Met polymorphism and protein levels in Amniotic Fluid Annamaria Cattaneo, Luisella Bocchio-Chiavetto, Roberta Zanardini, Eleonora Marchina, Daniela Bellotti, Elena Milanesi, Stefania Moraschi, Francesca Calabrese, Sergio Barlati, Marco Andrea Riva, Massimo Gennarelli BMC Neuroscience, 2010
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