Dear All,

We cordially invite you to the Ph.D. Seminar, which will be held on May 13, 2022 at 10.30 in the CN Conference Room (1st floor). The program includes 6 presentations:

1. Patrycja Dzianok
2. Jakub Wojciechowski
3. Maria Kulesza

Break (5-10 min)

4. Ewa Bączyńska
5. Karolina Nizińska-Smolińska
6. Paulina Pilanc-Kudlek

Information regarding speakers together with abstracts can be found below.

The seminar will be held in a hybrid mode. Link to the meeting

https://zoom.us/j/98063467206?pwd=RXFlbUUxRStmYnNlTnR1aFRTSHZGUT09

With best regards,

Anna Filipek & Anna Nowicka

Patrycja Dzianok

Laboratory of Emotions Neurobiology

Supervisor: Dr hab. Ewa Kublik

Auxiliary promoter: Dr Katarzyna Jurewicz

Title: Genetic variations in the APOE and PICALM Alzheimer’s disease risk-genes may be associated with health and cognitive functions in non-demented healthy adults

Abstract:

Alzheimer disease (AD) is the most common dementia causing global medical and social burden. Faster and more reliable diagnostic tests are needed just as much as effective therapies. AD results from a complex interplay of genetic, environmental and lifestyle factors. To understand this interplay, and find early biomarkers predicting cognitive decline, we must combine genomics within depth phenotyping of patients and non-symptomatic carriers of AD risk-genes.

For that reason, we invited healthy, middle-aged participants and collected a vast database with demographic, psychological, and genetic data (APOE/PICALM) along with medical blood tests and neuroimaging (high-density EEG and fMRI) data from resting state, attention related task (MSIT+) and memory related task (Sternberg).

Our current results show multiple differences between the groups carrying different genetic burdens, indicating that AD risk genes influence cognitive functions, psychosocial functioning, and health markers already in middle-aged healthy individuals. Further longitudinal studies are needed to confirm the observed associations.

Jakub Wojciechowski
Laboratory of Emotions Neurobiology
Supervisor I: Dr hab. Mateusz Gola
Supervisor II: Dr hab. Ewa Kublik

Title: Appetitive Conditioning and Extinction in CSBD Patients - fMRI study

Abstract:
The prevalence of problematic pornography use (PPU) in both adults and adolescents is increasing however there in no consensus whether it is strictly compulsive or addictive behavior. The latest ICD-11 finally included PPU under Compulsive Sexual Behavior Disorder (CSBD) unit, however the conditioning process in those patients seems to be altered, similar to addiction. Our study focused on the Ventral Striatum (VS) and Amygdala, which are part of the reward system, and their functional magnetic resonance (fMRI) activation during appetitive instrumental
conditioning and extinction in tasks with both erotic and monetary rewards.
Age-matched CSBD patients and healthy control subjects (n=32 in each group) participated in the study. In addition to measuring fMRI brain activity and reaction times in tasks, subjects also rated their arousal and valence toward cues before and after conditioning.
Preliminary results suggest that conditioning process is indeed altered in CSBD patients on both behavioral and functional level, although in a puzzling way. Supported by NCN Grant  2016/21/N/HS6/02635.

Maria Kulesza

Laboratory of Brain Imaging

Supervisor: Dr hab. Artur Marchewka, prof. IBD

Auxiliary promoter: Dr Marek Wypych

Title: Neural processing of emotionally charged autobiographical memories in women with major depressive disorder and borderline personality disorder

Abstract:
Our past experiences and knowledge about ourselves are stored in autobiographical memory (AM). Due to their emotional and sensory details, we are able to recall and relieve them. Previous studies showed a network of brain regions involved in AM recall in healthy populations, such as the limbic system, prefrontal, and occipital cortices.
AM recall may be disturbed in several clinical disorders, such as depression (MDD) or borderline personality disorder (BPD), where patients have difficulties with emotion regulation and processing the self. Some studies showed that patients recall fewer details and tend to recall more negative experiences.
Here, I compared the neural processing of sad (SM) and happy memories (HM) in women with MDD, BPD, and healthy control (HC) who were asked to recall and rate the memories during an fMRI session. Subjective emotional state after AMs was less positive in the BPD group than in HC. Moreover, within the MDD and HC groups, SMs were less vivid than HMs.
The main effect of recall showed robust activations across the AM recall network. The main effect of emotion revealed greater activations within this network in SMs. Functional connectivity analysis revealed increased connectivity between the left amygdala and right parietal operculum for SMs in the MDD group when compared to BPD. This could indicate that amygdala plays a different role in depression than in BPD.

Break  (5-10 min)

Ewa Bączyńska

Laboratory of Cell Biophysics

Supervisor: Prof. dr hab. Jakub Włodarczyk

Auxiliary promoter: Dr Monika Bijata

Title: Role of the 5-HT₇ receptor in the development of depressive-like behavior

Abstract:

Depression is a global medical problem frequently leading to suicides. It is assumed that depressive symptoms occur as a result of aberrant excitatory synaptic plasticity developed after chronic stress. Recently discovered a new 5-HT₇ serotonin receptor-dependent signaling pathway leads to aberrant structural and functional synaptic plasticity in the hippocampal neurons in vitro. It was shown that reactivity of the 5-HT₇ serotonin receptor (5-HT₇R) is strongly regulated by stress hormones, and possibly may underlie depressive symptoms. Using a combination of behavioral, biochemical, and imaging methods, we verified whether the 5-HT₇R is involved in the development of depressive-like behavior. Our results showed that activation of the 5-HT₇R leads to the development of depressive-like behavior in mice and that the 5-HT₇R-dependent signaling pathway is specifically activated in the hippocampus of anhedonic animals and associated with the structural remodeling of dendritic spines. The stress-resilient animals after chronic stress did not display the aforementioned alterations. Our results indicate the 5-HT₇R crucial role in the development of depressive phenotype and reveal an alternative direction for drug discovery in which mechanisms will promote stress resilience.

Karolina Nizińska-Smolińska

Laboratory of Epileptogenesis

Supervisor: Prof. dr hab. Katarzyna Łukasiuk

Title:  The role of Methyl-CpG binding domain 3 (MBD3) in epileptogenesis

Abstract: 

Epilepsy is a neurological disorder induced by a pathophysiologic process that is not fully understood. 30% of epilepsies are evoked by an insult to the brain which is followed by a latency period (epileptogenesis) before the appearance of spontaneous seizures. During epileptogenesis and epilepsy, several molecular and cellular changes occur, including alterations in gene and protein expression. MBD3 protein is a reader of DNA methylation marks that play an important role in epileptogenesis.

To determine changes in MBD3 protein level in the rat brain after seizure, we used rat model of acute seizure evoked by intraperitoneal injection of pentylenetetrazol (PTZ). Changes in Mbd3 expression and MBD3 protein level were examined in the hippocampus, entorhinal and somatosensory cortex. We observed an increased level of MBD3 protein in the entorhinal cortex 4h after PTZ injection.

In the next part we decided to test the hypothesis that modification of Mbd3 expression affects acute seizures. AAV viruses to increase (AAV-SYN-MBD3-GFP) and decrease (AAV-sh(MBD3)-GFP) Mbd3 expression were injected bilaterally (0,4µl) to the basolateral amygdala (BLA). Behavioral tests were performed 2 weeks after injection. Next, we performed PTZ test with EEG recording. Our results showed the reduction of MBD3 prolonged latency time to evoke acute seizure.

Paulina Pilanc-Kudlek

Laboratory of Molecular Neurobiology

Supervisor: Prof. dr hab. Bożena Kamińska-Kaczmarek

Auxiliary promoter: Dr Aleksandra Ellert-Miklaszewska

Title: Reprogramming of myeloid cells in the microenvironment of gliomas as a new therapeutic strategy          

Abstract:

Glioblastoma (GBM) is the most common and aggressive brain cancer, for which the current therapies are not effective and most tumors recur within few months. Immunotherapy using immune checkpoint inhibitors (CPI) aims to restore antitumor immune response. However, GBM patients respond poorly to immunotherapies as GBM is immunologically a “cold” tumor with low infiltration of functional T and natural killer (NK) cells. We aim to develop new strategies to reactivate antitumor immune responses in GBM and sensitize this tumor to CPI. These strategies infer targeting glioma-associated brain-resident microglia and recruited peripheral myeloid cells (GAMs), which contribute to the immunosuppressive tumor microenvironment (TME). Using a mouse glioma model, we applied two approaches: i) blocking the activity of arginase 1 (Arg1) with OAT-1746- a novel, potent and selective small molecule inhibitor, and ii) interfering with a protumoral action of glioma-derived osteopontin (Spp1) using a short integrin-blocking peptide. Expression of Arg1 is a defining feature of immunosuppressive GAMs and leads to depletion of L-arginine, a nutrient required for T cells and NK cells proliferation, while activation of integrin receptors by glioma-derived Spp1 is one of factors responsible for the protumorigenic switch of GAMs. Tumor growth was evaluated using MRI and immunosorting of GAMs combined with RNAseq transcriptomic profiling and multiparametric flow cytometry analysis allowed for characterization of immune infiltrates in the glioma TME. In both proposed strategies, targeting immunosuppressive GAMs as an adjuvant to CPI led to augmented antitumor activity that was due to boosting of both innate and adaptive immune responses.