Electrophysiological and Molecular Insights into Thalamocortical Rhythmicity and Hippocampal Theta Oscillations

Zusammenfassung Neuronale Netzwerke sind mit verschiedenen spannungsgesteuerten Kalziumkanälen verknüpft, die eine Schlüsselrolle in der Entstehung von Oszillationen im Hippocampus, aber auch in der thalamokortikalen Rhythmizität einnehmen. Innerhalb einer Vielzahl von Oszillationen konnte gezeigte werden, dass der Cav2.3 R-typ Kalziumkanal für die hippocampale Thetaaktivität maßgeblich verantwortlich ist. Thetaoszillationen im Frequenzbereich von 4-7 Hz repräsentieren ein spezifisches Aktivitätsmuster, das für kognitive Fertigkeiten, wie dem Abrufen von Gedächtnisinhalten, unerlässlich ist. Auf pharmakologischer Ebene werden zwei Subtypen von Thetaaktivität, der Atropin resistente Typ I und das Atropin sensitive Typ II Theta, differenziert. Typ II Theta wird dabei über eine durch den Cav2.3 R-typ Kalziumkanal vermittelte, muskarinerge Signalkaskade in der hippocampalen CA1 Region generiert. Interessanterweise treten Theta Oszillationen auch während des paradoxen bzw. REM (rapid eye movement) Schlafs auf, was daraufhin deutet, dass Thetaaktivität vom zirkadianen Rhythmus abhängt. Da Cav2.3 R-typ Kalziumkanäle ebenfalls im retikulär thalamischen Kern (RTN), der in die Schlafgenerierung eingebunden ist, exprimiert werden, kann vermutet werden, dass dem Cav2.3 Kalziumkanal eine regulatorische Funktion beim Schlaf zukommt. Bislang konnte allerdings nicht geklärt werden, welche genaue Rolle Cav2.3 R-typ Kalziumkanäle im thalamokortikalen Netzwerk übernehmen. Daher analysierten wir den Cav2.3 R-typ Kalziumkanal in spontanen und pharmakologisch induzierten Schlaf von Cav 2.3-/- Mäusen und Cav 2.3+/+ Kontrolltieren. Unsere Ergebnisse zeigen eine erhöhte Anzahl an Schlafübergängen sowie eine verminderte Gesamtwachdauer bei Cav 2.3-/- Mäusen und verdeutlichen folglich die tragende Rolle des Cav2.3 R-typ Kalziumkanals in Bezug auf die Schlafmodulation. Studien belegen, dass Cav2.3-/- Mäuse auch Absence-Epilepsien ausbilden können, was die Rolle des Cav2.3 R-typ Kalziumkanals in der Epileptogenese widerspiegelt. Pathologische Veränderungen in der zentralen Rhythmizität und eine damit einhergehende erhöhte Anfallswahrscheinlichkeit können unter anderem durch Akkumulation von Aß Plaques, wie sie bei der Alzheimererkrankung auftreten, gefördert werden. Dabei zeigte sich, dass in Mausmodellen der familiären Alzheimer-Demenz (FAD) erhöhte Aß Plaquebildung mit Veränderungen in der Proteinsynthese vom BACE1 Enzym (ß-site APP cleaving enzyme 1) einhergeht. In diesem Zusammenhang ist eine gesteigerte Translation des BACE1 Enzyms unmittelbar an die 6 Phosphorylierung vom Serin an Position 51 des eukaryotischen Translationsinitiationsfaktors 2 Alpha (elF2α) gebunden. Diese Tatsache wirft die Frage auf, ob eine Runterregulierung von elF2α zu einer geringeren Anfallswahrscheinlichkeit durch verminderte Plaquebildung beiträgt und somit den kognitiven Verfall in 5XFAD Mäusen verzögern kann. Dazu untersuchten wir mögliche präventive Effekte von elF2α auf die Epileptogenese, indem wir 5XFAD Mäuse mit einer elF2αS51A Knock-in Line kreuzten, bei denen, durch eine Substitution von Serin durch Alanin an Position 51 bedingt, elF2α nicht mehr phosphoryliert werden kann. Unsere Ergebnisse zeigen einen limitierten präventiven Effekt von elF2α auf motorische und kognitive Defizite in 5XFAD Mäusen. Veränderungen im Hippocampus gehen mit elektrophysiologischen Befunden einher, welche nicht-konvulsive Statusformen epileptiformer Aktivität bei 5XFAD Tieren mit elF2αS51A Allel belegen. Weiterhin untersuchten wir, wie sich Anfallsaktivität auf die muskaringere Signalkaskade in 5XFAD Mäusen auswirkt. Wir stellten fest, dass eine verstärkte muskarinerge Signalkaskade sowohl zu neuronaler Dysrhythmie, aber auch zu einer Erhöhung von Atropin sensitiven Typ II Theta beiträgt, die als möglicher Kompensationsmechanismus zu einem dysbalancierten neuronalen System bei Morbus Alzheimer in Betracht gezogen werden kann

Subtypes of interictal depressive disorders according to ICD-10 in patients with epilepsy

Background and purpose: The purpose of the study was to evaluate the frequency of interictal depressive symptoms and different subtypes of depressive disorders according to 10th revision of the International Classification of Diseases (ICD-10) criteria in patients with epilepsy and its association with the type of epilepsy. Material and methods: 289 outpatients with epilepsy (169 females, 120 males) aged 18-82 years completed Beck Depression Inventory (BDI). Subjects who scored >11 in BDI were further evaluated by the psychiatrist according to the ICD-10 diagnostic criteria. Results: 41.9% (121) of the 289 participants scored >11 in BDI. 104 (85.9%) patients who scored >11 in BDI had comorbid mental disorders according to ICD-10 criteria. The most common were organic mood disorders (F06.3 – 31.4%), depressive episode (F32 – 22.3%) and dysthymia (F34.1 – 9.1%) There were no differences in the prevalence of depression and subtypes of depression in patients with certain epilepsy types. Depression was diagnosed before entering the study in only one third of patients with final diagnosis of depression. Conclusions: Our results confirm the prevailing view that interictal depression is common in epilepsy patients. Depression remains underrecognized and undertreated in patients with epileps

Subtypes of interictal depressive disorders according to ICD-10 in patients with epilepsy

Background and purpose The purpose of the study was to evaluate the frequency of interictal depressive symptoms and different subtypes of depressive disorders according to 10th revision of the International Classification of Diseases (ICD-10) criteria in patients with epilepsy and its association with the type of epilepsy. Material and methods 289 outpatients with epilepsy (169 females, 120 males) aged 18–82 years completed Beck Depression Inventory (BDI). Subjects who scored >11 in BDI were further evaluated by the psychiatrist according to the ICD-10 diagnostic criteria. Results 41.9% (121) of the 289 participants scored >11 in BDI. 104 (85.9%) patients who scored >11 in BDI had comorbid mental disorders according to ICD-10 criteria. The most common were organic mood disorders (F06.3 – 31.4%), depressive episode (F32 – 22.3%) and dysthymia (F34.1 – 9.1%) There were no differences in the prevalence of depression and subtypes of depression in patients with certain epilepsy types. Depression was diagnosed before entering the study in only one third of patients with final diagnosis of depression. Conclusions Our results confirm the prevailing view that interictal depression is common in epilepsy patients. Depression remains underrecognized and undertreated in patients with epilepsy

Depressogenic medications and other risk factors for depression among Polish patients with epilepsy

PURPOSE: The aim of this study was to assess the prevalence of depression among patients with epilepsy and to establish the risk factors of depression in that group, with special focus on the use of potentially depressogenic medications. PATIENTS AND METHODS: We studied 289 consecutive patients who visited epilepsy outpatient clinic (University Hospital of Krakow) and met inclusion criteria. All patients were screened with Beck Depression Inventory (BDI), and those with BDI score ≥12 were further evaluated by a psychiatrist. RESULTS: Mean age of patients was 35.7 years, and mean duration of epilepsy was 14.7 years. Idiopathic generalized epilepsy was diagnosed in 63 patients (21.8%), focal epilepsy was found in 189 subjects (65.4%), and unclassified epilepsy was diagnosed in 37 patients (12.8%). Frequent seizures (>1 per month) were reported in 107 patients (37.0%). Thirty-five patients (12.1%) reported an ongoing treatment with one or more of the predefined potentially depressogenic medication (β-blockers, combined estrogen and progestogen, corticosteroid, or flunarizine). In a group of 115 patients (39.8%) who scored ≥12 points in BDI, depression was finally diagnosed in 84 subjects (29.1%) after psychiatric evaluation. Only 20 of those patients (23.8%) were treated with antidepressant. Independent variables associated with the diagnosis of depression in the logistic regression model included frequent seizures (odds ratio [OR] =2.43 [95% confidence interval, 95% CI =1.38–4.29], P=0.002), use of potentially depression-inducing medications (OR =3.33 [95% CI =1.50–7.39], P=0.003), age (OR =1.03 [95% CI =1.01–1.05] per year], P=0.005), and use of oxcarbazepine (OR =2.26 [95% CI =1.04–4.9], P=0.038). CONCLUSION: The prevalence of depression among consecutive Polish patients with epilepsy reached 29.1%. Less than quarter of them received antidepressant treatment at the moment of evaluation. Independent variables associated with depression included age, frequent seizures, and the use of oxcarbazepine or predefined depressogenic medications

Suicidality and its determinants among Polish patients with epilepsy

Background and purpose The aim of this study was to evaluate the prevalence of suicidal ideation among Polish patients with epilepsy and to assess the potential determinants of suicidality in this cohort. Material and methods The study comprised 301 patients with epilepsy seen in the tertiary epilepsy clinic. Patients’ characteristics included demographic variables, epilepsy-related variables, as well as occurrence of comorbidities, ongoing use of any other medications, family history of epilepsy and/or depression. Beck Depression Inventory (BDI) was used to assess depressive symptoms, and question no. 9 of BDI was specifically used to reveal suicidality. Results Mean age of subjects was 35.5 years. 113 (37.5%) had frequent seizures and 96 patients (31.9%) had remission. BDI score>11 points (suggestive for depression) was found in 127 subjects. Suicidal ideation has been revealed in 30 (10.0%) out of 301 studied patients. Patients with suicidal ideation were older and more commonly reported frequent seizures. Almost all of them (93.3%) had clinically significant depressive symptoms (BDI score>11). Multivariate analysis revealed that severity of depressive symptoms (OR=1.16 per one-point increase in BDI score, 95% CI: 1.10–1.22, p<0.001) and the use of potentially depressogenic medication (OR=3.04, 95% CI: 1.04–8.89, p=0.04) were independent determinants of suicidality among studied patients. Conclusions Suicidal ideations were revealed by about 10% of studied epileptic patients who visited tertiary center for epilepsy. Independent predictors of suicidality among studied patients included depression itself and the use of potentially depressogenic medication

Suicidality and its determinants among Polish patients with epilepsy

Background and purpose The aim of this study was to evaluate the prevalence of suicidal ideation among Polish patients with epilepsy and to assess the potential determinants of suicidality in this cohort. Material and methods The study comprised 301 patients with epilepsy seen in the tertiary epilepsy clinic. Patients’ characteristics included demographic variables, epilepsy-related variables, as well as occurrence of comorbidities, ongoing use of any other medications, family history of epilepsy and/or depression. Beck Depression Inventory (BDI) was used to assess depressive symptoms, and question no. 9 of BDI was specifically used to reveal suicidality. Results Mean age of subjects was 35.5 years. 113 (37.5%) had frequent seizures and 96 patients (31.9%) had remission. BDI score>11 points (suggestive for depression) was found in 127 subjects. Suicidal ideation has been revealed in 30 (10.0%) out of 301 studied patients. Patients with suicidal ideation were older and more commonly reported frequent seizures. Almost all of them (93.3%) had clinically significant depressive symptoms (BDI score>11). Multivariate analysis revealed that severity of depressive symptoms (OR=1.16 per one-point increase in BDI score, 95% CI: 1.10–1.22, p<0.001) and the use of potentially depressogenic medication (OR=3.04, 95% CI: 1.04–8.89, p=0.04) were independent determinants of suicidality among studied patients. Conclusions Suicidal ideations were revealed by about 10% of studied epileptic patients who visited tertiary center for epilepsy. Independent predictors of suicidality among studied patients included depression itself and the use of potentially depressogenic medication

HAMMERSHUS - DOBRE PRAKTYKI I ZARZĄDZANIE TRWAŁĄ RUINĄ

Hammershus is a medieval Danish castle on the Bornholm island. In 1743 Hammershus was finally abandoned as a stronghold. The fortress was partially demolished around 1750. The ruins were put on the national historic register in 1822. From 1885, until his death in 1928, P. C. Hauberg was in charge of the extensive restoration work. After that, the castle remained a picturesque ruin. The conservation policy, which was taken from 1907, includes the purchase of land around the castle and systematic removal of the surrounding buildings. In 1969 Jørn Utzon created the concept of the information center hidden in the landscape. In 2013, his concept was implemented. The project was developed by the Danish team Arkitema, in cooperation with Buro Happold, and Ch. Harlang. The modern information center put into use in 2018. Building is removed from the ruins and hidden in the nearby slope. The protection of Hammershus Castle is subordinated to preserving its historical form - a permanent ruin. It is also conducted in the landscape sphere. The new reception center was located and designed so as to not compete with the historical ruin and landscape. The Hammershus castle management model is an example of good practice in protecting cultural heritage and historic ruins. The main point is to use the attractiveness of the historical ruins, as an object that attracts visitors.The remoteness of modern commercial functions from the monument create new possibilities for contemplating the castle ruins and contributes to strict landscape protection.Zamek Hammershus, to średniowieczna, duńska warownia na wyspie Bornholm. W ruinie od połowy XVIII w. Dewastację powstrzymano w 1822, gdy ruinę zamku uznano za zabytek. Zamek, dominujący w widokach północnego wybrzeża wyspy stał się celem wędrówek romantycznych turystów. Decydujące prace konserwatorskie przeprowadził Peter Hauberg w latach 1885 – 1928, programowo powstrzymując się od rekonstrukcji. Funkcje recepcyjne pomieszczono w zabudowaniach opodal ruin. Polityka ochronna prowadzona od 1907 r. wiązała się z wykupem terenów wokół zamku i systematycznym usuwaniem okolicznych budowli. W 1969r. koncepcję centrum informacyjnego, ukrytego w krajobrazie stworzył Jørn Utzon. W 2013 podjęto realizację jego koncepcji. Projekt opracował duński zespół Arkitema, we współpracy z Buro Happold, i Ch. Harlangiem. Nowoczesne centrum interpretacji zabytku oddane do użytku w 2018 r. jest odsunięte od ruin i ukryte w formach terenu. Ochrona zamku Hammershus jest podporządkowana zachowaniu jego historycznej formy – trwałej ruiny. Jest również prowadzona w sferze krajobrazowej. Nowe centrum recepcyjne zlokalizowano i zaprojektowano tak, by nie konkurowało z formą historyczną i krajobrazem. Model zarządzania zamku Hammershus to przykład dobrej praktyki w ochronie dziedzictwa kulturowego i zabytkowych ruin. Istotą jest wykorzystanie atrakcyjności ruiny historycznej, jako obiektu przyciągającego odwiedzających oraz oddalenie współczesnych funkcji komercyjnych od zabytku wraz ze stworzeniem nowych możliwości kontemplacji zabytku oraz rygorystyczną ochroną krajobrazu

Temperature of spring water in Polonina Wetlinska massif

The temperature of spring water reflects recharge condition, depth, and circulation time of supplying with ground water. The aim of the study was to characterize spring water temperature in Polonina Wetlinska massif and to determine the factors controlling its spatial diversity and seasonal changes. The data from field mapping in 2010 and 2011 were used along with data collected in 2012-14 by automatic data logger. Neither regularity in spatial diversity of spring water temperature was identified nor was relation with elevation and slope exposition. On the other hand a dependency between spring water temperature and type of outflow (rheocrene/bog springs) was observed, which was controlled by the heating process of groundwater in spring niche. The same mechanism controlled the higher temperature of water in springs of low discharge than observed in the most abundant ones. The temperature of monitored spring were stable throughout the year - the annual amplitude did not exceed 2^{\circ}C. Two types of thermal regime were identified

Psychiatric aspect of most common used cardiological drugs

Introduction: The count of psychiatric patients is growing. The same trend it is observed among cardiovascular diseases and metabolic like diabetes. Many people take drugs which may affect on mental state. On the one hand that drugs could have pleotropic mechanism of action which are beginning to use in treatment of psychiatry. The other hand is showed undiscovered field of impact on brain working.    Methods and Aim: Shown the psychiatric aspect, like side effects and unusual use, of the most used cardiological drugs. To do this, research of articles was done with the help of deta bases such as PubMed and Google Scholar.Results: The most used cardiological drugs are beta blockers, calcium canal blockers, ACE inhibtors, ARBs, nitrats, cilostazol, amiodarone and clonidine In this article it was shown current known about those drugs like mechanism of action and a report of psychiatric clinical trials. Beta-blockers are the most commonly used group of cardiological drugs as the one that significantly affects mental health. Their therapeutic importance has been noted in diseases such as: PTSD or stage fright. It was also long believed that they could make depression worse, but the latest research strongly contradicts this. A positive effect in the treatment of depression can also be obtained by usage of inhibitors of the RAA. Calcium channel blockers are another group of cardiac drugs that are important in the regulation of mood in bipolar disorder. To sum up, a large proportion of cardiac drugs can influence the flow of psychiatric diseases, and the use of them may be clinically desirable in patients with both - cardiac and psychiatric problems