Marinos G Sotiropoulos, Eleni Poulogiannopoulou, Foteini Delis, Christina Dalla, Katerina Antoniou, and Nikolaos Kokras. 2021. “Innovative screening models for the discovery of new schizophrenia drug therapies: An integrated approach.” Expert Opin Drug Discov.Abstract
: Schizophrenia is a severe psychiatric disorder affecting millions of people worldwide. However, available treatment options do not fully address the disease. Whereas current antipsychotics may control psychotic symptoms, they seem notoriously ineffective in improving negative and cognitive symptoms or in preventing functional decline. As the etiology of schizophrenia eludes us, the development of valid animal models for screening new drug targets appears to be a strenuous task. Areas covered In this review, the authors present the key concepts that validate animal models of schizophrenia, as well as the different screening approaches for novel schizophrenia treatments. The models covered are either based on major neurotransmitter systems or neurodevelopmental, immune and genetic approaches. Expert opinion Sadly, due to inertia, research focuses on developing "anti-psychotics", instead of "anti-schizophrenia" drugs that would tackle the entire syndrome of schizophrenia. Whereas no perfect model may ever exist, combining different experimental designs may enhance validity, as the over-reliance on a single model is inappropriate. Multi-model approaches incorporating vulnerability, the "two-hit" hypothesis and endophenotypes offer a promise for developing new strategies for schizophrenia treatment. Forward and reverse translation between preclinical and clinical research will increase the probability of success and limit early or late-stage failures in drug development.
Aikaterini Dedeilia and Marinos G Sotiropoulos. 2020. “Achieving 'impossible' career goals: antimentoring and uncalled-for landmines in the pursuit of happiness and equal opportunity.” Postgrad Med J.
Nikolaos Kokras, Eleni Poulogiannopoulou, Marinos G Sotiropoulos, Rafaella Paravatou, Eleni Goudani, Maria Dimitriadou, Electra Papakonstantinou, George Doxastakis, Despina N Perrea, George Hloupis, Apostolis Angelis, Aikaterini Argyropoulou, Anthony Tsarbopoulos, Alexios-Leandros Skaltsounis, and Christina Dalla. 2020. “Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Extract in Female Mice.” Molecules, 25, 21.Abstract
The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals' overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.
Stefanos Karamaroudis, Eleni Poulogiannopoulou, Marinos G Sotiropoulos, Thomas Kalantzis, and Elizabeth O Johnson. 2020. “Implementing Change in Neuroanatomy Education: Organization, Evolution, and Assessment of a Near-Peer Teaching Program in an Undergraduate Medical School in Greece.” Anat Sci Educ, 13, 6, Pp. 694-706.Abstract
In light of the current shifts in medical education from traditional lectures to more active teaching modalities, a peer-teaching program was introduced to a compulsory, second-year neuroanatomy course. A cross-sectional survey of 527 medical students in the six-year medical program of the National and Kapodistrian University of Athens was administered. The primary aim of the survey, which was distributed to second- through sixth-year medical students, who had completed the neuroanatomy course, was to assess student perception of peer teachers (PTs). Across the five years assessed, students increasingly acknowledged the contribution of PTs to their learning (P < 0.001). Attributes of PTs (e.g., contribution to learning, motivation, effective usage of material, and team environment) were significantly related to the student's opinion of the importance of laboratory activities (P < 0.001). Students who received "average" final grades scored the importance of laboratory exercises, and by inference PTs, significantly lower than students who received "excellent" final grades (P < 0.05). The amount of training that PTs had received was also significantly related to student perceptions of a PT's contribution. Better trained PTs were associated with significantly higher scores regarding learning, motivation, and positive environment compared to less trained PTs (P < 0.05). The results of the present study show that peer-teaching was well received by students attending the neuroanatomy course. While the results express the evolution of the program across the years, the findings also show that learners believed that PTs and the laboratory program contributed significantly to their understanding of neuroanatomy.
Marinos G Sotiropoulos. 2020. “Impostor syndrome: a calling for a career in medical education?” Postgrad Med J.
Aikaterini Dedeilia, Marinos G Sotiropoulos, John Gerrard Hanrahan, Deepa Janga, Panagiotis Dedeilias, and Michail Sideris. 2020. “Medical and Surgical Education Challenges and Innovations in the COVID-19 Era: A Systematic Review.” In Vivo, 34, 3 Suppl, Pp. 1603-1611.Abstract
The aim of this systematic review was to identify the challenges imposed on medical and surgical education by the COVID-19 pandemic, and the proposed innovations enabling the continuation of medical student and resident training. A systematic review on the MEDLINE and EMBASE databases was performed on April 18th, 2020, and yielded 1288 articles. Sixty-one of the included manuscripts were synthesized in a qualitative description focused on two major axes, "challenges" and "innovative solutions", and two minor axes, "mental health" and "medical students in the frontlines". Shortage of personal protective equipment, suspension of clinical clerkships and observerships and reduction in elective surgical cases unavoidably affect medical and surgical education. Interesting solutions involving the use of virtual learning, videoconferencing, social media and telemedicine could effectively tackle the sudden cease in medical education. Furthermore, trainee's mental health should be safeguarded, and medical students can be involved in the COVID-19 clinical treatment if needed.
Marinos G Sotiropoulos and Tanuja Chitnis. 2020. “Opposing and potentially antagonistic effects of BMP and TGF-β in multiple sclerosis: The "Yin and Yang" of neuro-immune Signaling.” J Neuroimmunol, 347, Pp. 577358.Abstract
Bone Morphogenetic Proteins (BMP) and Transforming Growth Factor-beta (TGF-β) are cytokines with similar receptors and messengers. They are important for immune cell function, with BMPs exerting mainly proinflammatory but also anti-inflammatory effects, and TGF-β suppressing inflammation. Patients with Multiple Sclerosis exhibit BMP overactivity and suppressed TGF-β signaling. This dysregulated signaling participates in the crosstalk between infiltrating immune cells and glia, where BMP inhibits remyelination. Reciprocal antagonism between the two pathways takes place via a variety of mechanisms. Although this antagonism has not been studied in the setting of Multiple Sclerosis, it could inform further research and treatment discovery.
Marinos G Sotiropoulos. 2020. “The Patient I Didn't Like.” JAMA Neurol, 77, 1, Pp. 11-12.
Nikolaos Kokras, Chrysoula Dioli, Rafaella Paravatou, Marinos G Sotiropoulos, Foteini Delis, Katerina Antoniou, Theodora Calogeropoulou, Ioannis Charalampopoulos, Achille Gravanis, and Christina Dalla. 2020. “Psychoactive properties of BNN27, a novel neurosteroid derivate, in male and female rats.” Psychopharmacology (Berl), 237, 8, Pp. 2435-2449.Abstract
RATIONALE: Νeurosteroids, like dehydroepiandrosterone (DHEA), play an important role in neurodegeneration and neural protection, but they are metabolized in androgens, estrogens, or other active metabolites. A newly developed synthetic DHEA analog, BNN27 ((20R)-3β,21-dihydroxy-17R,20-epoxy-5-pregnene), exerts neurotrophic and neuroprotective actions without estrogenic or androgenic effects. OBJECTIVES: This study aimed to investigate potential anxiolytic or antidepressant properties of BNN27. METHODS: Male and female adult Wistar rats were treated with BNN27 (10, 30, or 90 mg/kg, i.p.) and subjected to behavioral tests measuring locomotion, exploration, and "depressive-like" behavior (open field, light/dark box, hole-board, and forced swim tests). The hippocampus and prefrontal cortex were collected for glutamate and GABA measurements, and trunk blood was collected for gonadal hormone analysis. RESULTS: Acute high-dose BNN27 reduced locomotion and exploratory behavior in both sexes. Intermediate acute doses (30 mg/kg) of BNN27 reduced exploration and testosterone levels only in males, and enhanced progesterone levels in both sexes. Notably, with the present design, BNN27 had neither anxiolytic nor antidepressant effects and did not affect estrogen levels. Interestingly, acute administration of a low BNN27 dose (10 mg/kg) increased glutamate turnover, GABA, and glutamine levels in the hippocampus. The same dose also enhanced glutamate levels in the prefrontal cortex of males only. Sex differences were apparent in the basal levels of behavioral, hormonal, and neurochemical parameters, as expected. CONCLUSIONS: BNN27 affects locomotion, progesterone, and testosterone levels, as well as the glutamatergic and GABAergic systems of the hippocampus and prefrontal cortex in a sex-dependent way.
Marinos G. Sotiropoulos. 2020. “Impostor syndrome: a calling for a career in medical education?” Postgrad Med J. Publisher's Version
Nikolaos Kokras, Marinos G Sotiropoulos, Eleni Poulogiannopoulou, and Christina Dalla. 2019. “Maternal and Infant Pharmacokinetics of Psychotropic Medications During Pregnancy and Lactation.” In Perinatal Psychopharmacology, Pp. 17–35. Springer.