Neuropsychopharmacology Application and Research Center - Neurochemistry Laboratory (NPFUAM - NKL) was established at the beginning of 2018 within NPFUAM at Üsküdar University, which has the vision of a thematic university in the field of neuroscience.
The Neurochemistry Laboratory within NPFUAM, one of the few centers in the field of neuropsychopharmacology in the world and the only center in this field in our country, has taken the vision and goals of NPFUAM one step further and focused on understanding the neurochemical balance in the central nervous system for both etiological and pharmacological purposes and mapping neurochemical systems in the mammalian brain.
Vision
The main vision of NPFUAM NKL is to understand the chemical structure and function of the brain from micro to macro level, from intracellular molecular pathways and molecular systems that elicit neural function at the single cell level, to neurotransmitters that enable communication between neurons and the systems that these neurotransmitters form in the brain. More specifically, a neurochemical mapping of regions and subsystems that are prominent in neurodevelopmental disorders is the focus of the laboratory.
Objectives
The main goal of NPFUAM-NKL is to investigate the neurochemical mechanisms of neural disorders such as Alzheimer's, schizophrenia, autism, epilepsy, anxiety, depression and sleep disorders in order to investigate their origins and develop pharmacological applications.
Current studies conducted at NPFUAM-NKL focus on neurodevelopmental processes and disorders related to these processes.
Methods
Current studies at NPFUAM-NKL are based on in vivo models of neural disorders developed at NPFUAM. In this way, studies conducted at NPFUAM-NKL are associated with various behavioral and physiological phenotypes, providing a broader picture of the disorders studied.
Facilities and methods available in the laboratory:
- Preparation of frozen sections from fixed or fresh tissue samples,
- Tissue morphology and pathology examinations with basic histological staining (Hematoxylin-Eosin, Nissl staining, etc.)
- Investigation of neurochemical markers by immunohistochemistry and mapping in the whole brain,
- Chemical content analysis of tissue samples by thin layer chromatography
- Transparency and isolation of whole extracellular matrix in brain sections
- Examination of markers in cell culture models by immunocytochemistry
- Model generation based on experimental results with computational neuroscience and bioinformatics techniques
Current Studies Conducted at NPFUAM-NKL
Behavioral symptoms in a sleep deprivation model and the orexinergic system in adult neurogenesis
Support: TUBITAK 3501 Career Development Program (117S353)
Project Team:
Executor: Prof. Dr. Lecturer Member Pınar Öz
Advisor: Prof. Dr. Tayfun Uzbay
Graduate Students: Gül Öncü, Seda Özdamar
The first part of our study was based on the sleep deprivation model and behavioral investigations developed at NPFUAM and the second part was based on immunohistochemical investigations performed at NPFUAM-NKL.
It is known that new neuron production continues in two main regions of the adult brain [subventricular zone (SVZ) and hippocampal subgranular zone (SGZ)]. The proliferation, differentiation and migration behaviors of adult neural stem cells are disrupted by sleep deprivation and the SGZ becomes an interesting target region considering its role in long-term memory. Seventy-two hours of REM deprivation is a widely accepted model for modeling psychotic disorders in rats.
In our study, we first investigate the relationship between changes in hippocampal adult neurogenesis in healthy rats and the pre-stimulus-mediated inhibition (PMRI) response, which is considered an endophenotype in disorders such as schizophrenia. In the second stage, the effect of the orexinergic system on this relationship is examined, and in the third stage, the role of the orexinergic system in the sleep deprivation- adult neurogenesis- OSAI triangle is examined.
Biologically-derived scaffold design by isolation of whole extracellular matrix from rat hippocampus for use in neural stem cell cultures
Project Team:
Executor: Prof. Dr. Lecturer Prof. Dr. Pınar Öz
Researcher Prof. Dr. Lecturer. Prof. Dr. Zeynep Kanlıdere
Undergraduate Student Nurdan Çam
Primary neural stem cell cultures derived from the adult hippocampus play an important role for studying neurogenesis processes in this environment and developing pharmacological applications. Three-dimensional scaffolds prepared by isolating the physical structure of the microenvironment that regulates adult neurogenesis in vivo and guiding biomarkers can be used to create a realistic environment for studying the processes in vitro. For this purpose, the first preliminary studies on the isolation, characterization and in vitro testing of all ESM from various brain regions, primarily hippocampal regions, and from both fixed and fresh tissue were carried out at NPFUAM NKL in 2018 and have reached the project design stage. Studies are ongoing.
Future Studies Planned at NPFUAM-NKL
Research to identify genetic and biochemical factors, i.e. biomarkers, associated with neurological disease
Developed in rats and mice at NPFUAM
- Models of neurodevelopmental disorders induced by valproic acid
- 72 hours REM sleep disturbance model
- Model of depression with forced swimming test
- Models of OSAI disorder with pharmacological applications
- Stereotaxic lesion and microinjection-generated surgical models
- Addiction models
- Epilepsy models
Detailed research on neurotransmitter systems and genetic/epigenetic markers in in vivo models such as in vivo models is planned.
In addition,
- Our laboratory will also be able to support human studies with detailed neurochemical analysis of blood or tissue samples.
- Studies in which similar neurochemical analyses will be performed in cellular models developed in vitro are planned.
- We plan to conduct in silico studies on receptor-ligand interactions and proteomic analysis of data obtained from broad-based databases or experimental methods.
Investigation of peptide and oligonucleotide-based drugs to treat neurological diseases
The obstacles to the success of peptide and oligonucleotide-based drugs are their inability to cross the blood brain barrier and their degradation by nucleases. Our aim is to use synthetic peptides and oligonucleotides with altered chemical structures so that peptides and oligonucleotides can cross the blood brain barrier in neurological research.
Antisense oligonucleotide technology is another area of research. Antisense oligonucleotides hybridize with mRNA and inhibit protein expression. We aim to investigate new generation antisense oligonucleotides prepared with chemical modifications that can cross the blood brain barrier and are resistant to nucleases on neurological diseases. Contact Laboratory Supervisor: Prof. Dr. Lecturer. Prof. Dr. Pınar Öz E-mail: pinar.oz@uskudar.edu.tr
