Project promoter: Tallinn University of Technology

Slides:



Advertisements
Similar presentations
Parkinson’s disease (PD) is one of the most common chronic progressive neurodegenerative diseases. PD has a prevalence of 1.2 million people in Europe.
Advertisements

Cellular Mechanisms of Learning
1 Activity-dependent Development (2) Hebb’s hypothesis Hebbian plasticity in visual system Cellular mechanism of Hebbian plasticity.
Topic 1: It’s My Body Part 2: Nervous System. Human Organ Systems SkeletalMuscular CirculatoryImmune RespiratoryDigestive ExcretoryReproductive NervousEndocrine.
AMPAKINE Compounds for the Treatment of Rett Syndrome
THE NERVOUS SYSTEM. Brain WHAT PARTS DO YOU KNOW THAT ARE IN THE NERVOUS SYSTEM? Spinal Cord Peripheral Nerves.
By Desmond Hanan THE NERVOUS SYSTEM. WHAT DOES IT DO? The nervous system is the part of the body that is in charge of data processing and controls an.
Molecular mechanisms of memory. How does the brain achieve Hebbian plasticity? How is the co-activity of presynaptic and postsynaptic cells registered.
Chapter The anatomy of a neuron. The mechanisms of impulse transmission in a neuron. The process that leads to release of neurotransmitter, and.
Nervous System.
BIPN 148 Lecture 15. Calcium regulation of gene expression.
Mechanisms for memory: Introduction to LTP Bailey Lorv Psych 3FA3 November 15, 2010.
The Generation and Survival of Nerve Cells
Slide 1 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Bear: Neuroscience: Exploring.
Nervous Systems Three Main Functions: 1. Sensory Input 2. Integration 3. Motor Output.
Figure 23.1 Growth cones guide axons in the developing nervous system.
Intro to the Nervous System Lesson 2. The Nervous Systems  The nervous system regulates body processes and structures to help maintain homeostasis. Its.
Nervous System
Physiology and Behavior: Neurotransmission
Ch  Nearly all multicellular organisms have communication systems  Specialized cells carry messages from one cell to another.  NERVOUS SYSTEM.
NETWORK INTERACTIONS IN SZ – THERAPEUTIC IMPLICATIONS
By: Dustin Horn.
The importance of international research cooperation:
Neurobiological Theories of Mental Disorders
CHAPTER 48 NERVOUS SYSTEMS.
Neurons and Nervous Systems
BDNF Seminar Spring 2010 Maneeshi Prasad Jan 29th 2010.
BIOLOGY AND CRIMINAL BEHAVIOR
Memory, Learning and BDNF gene expression
Contributions of BDNF to the Maturation of Cortical Inhibitory Circuits Ali Hamodi.
Early brain development part two
Cell Communication Chapter 11.
THE NERVOUS SYSTEM Xiaoming Zhang Department of Human Anatomy
Carl W. Cotman, Nicole C. Berchtold  Trends in Neurosciences 
Brain Extracellular Matrix in Health and Disease
Copyright Pearson Prentice Hall
Nitric Oxide (NO) and How it Regulates Motor Function
Nervous System and The Brain
Ch. 7: Neurons: Matter of the Mind Ch. 8: The Nervous System
Neuron Function.
Nervous System and The Brain
Neuron Structure & Function
Neurons, Synapses, and Signaling
Learning, Memory, Language
Ms. Scribner’s Biology class
Acetylation Unleashes Protein Demons of Dementia
Developmental neuroplasticity
Chapters 48 & 49 Campbell Biology – 9th ed.
Communication in the Nervous System
Memory Gateway to Learning.
Long term potentiation and depression
Knowledge Organiser – Homeostasis and the Human Nervous System
Cell Communication.
How does an axon grow? Compare the processes of axonal regeneration in peripheral and central nervous system. Dr Sanjay Manohar University of Oxford
THE NERVOUS SYSTEM.
Psychiatric Disorders: Diagnosis to Therapy
The Autistic Neuron: Troubled Translation?
Nervous System Communication
Psychology (9th edition) David Myers
Bonnie E Lonze, David D Ginty  Neuron 
The Nervous System.
Brain Function for Law-Neuro
Psychiatric Disorders: Diagnosis to Therapy
The Biological Basis of Behavior
Volume 88, Issue 5, Pages (December 2015)
Bridging animal and human models of exercise-induced brain plasticity
Neuroscience: Exploring the Brain, 3e
Volume 20, Issue 1, Pages R31-R36 (January 2010)
Dendritic Tau in Alzheimer’s Disease
Homeostatic Systems and Drugs
Presentation transcript:

Activity-dependent regulation of BDNF and Arc: master genes in synaptic plasticity Project promoter: Tallinn University of Technology Principal investigator: Tõnis Timmusk Donor project partner: University of Bergen Principal investigator: Clive R. Bramham Laulasmaa 21.09.2017

Examples of the Variety of Nerve Cell Morphologies Found in the Human Nervous System PN01012.JPG

Neurotrophic hypothesis

In vertebrates, ~50% neurons are lost during development In vertebrates, ~50% neurons are lost during development. Most of neurons die around the time when the targets are innervated Viktor Hamburger 1900-2001 Rita Levi-Montalcini 1909-2012 Joined Wash.U: 1934 1947

Lab of Molecular Neurobiology at TUT: gene regulation and signaling in the nervous system Model organisms: mice and men Genes: neurotrophic factors and their receptors Diseases: neuropsychiatric and neurodegenerative Potential drugs: neurotrophic factors

Why is the project needed? Modifiability of neuronal connectivity by formation of new synapses, and alteration of the strength and stability of existing synapses, is regarded as the main cellular basis for memory and long-term behavioral adaptations. The genes encoding neurotrophin BDNF and activity-regulated cytoskeleton-associated protein ARC are considered to be the master genes of synaptic plasticity. Knowledge about the regulatory mechanisms of BDNF and ARC gene is important both for understanding of molecular basis of learning and memory and for finding new drug targets for the treatment of several nervous system diseases.

Neurodegenerative diseases and neurotrophic factors BDNF GDNF, NRTN, BDNF, CDNF caudate nucleus and putamen substantia nigra HD normal PD normal hippocampus and cerebral cortex 6-OHDA GDNF CDNF spinal cord NGF, BDNF GDNF, BDNF normal AD Stephen Hawking normal ALS

What is the objective of the project? We aim to understand how synapses, the junctions across which a nerve impulse passes from an axon terminal to another neuron, function. More specifically, to study: (1) Regulation of BDNF gene transcription by its receptor TrkB signaling (2) Regulation of BDNF and Arc translatability by membrane depolarization and TrkB signaling BDNF hypothesis of synaptic consolidation. C.R. Bramham, E. Messaoudi / Progress in Neurobiology 76 (2005)

What did the project achieve? The results of the present research proposal about the regulatory mechanisms of BDNF and Arc genes will help to better understand the development and functioning of nervous system. Dysregulation of BDNF levels and/or its receptor TrkB activity are accompanied by and are believed to lead to several pathologies, particularly nervous system diseases like neuro-degenerative, psychiatric and cognitive diseases. It is widely accepted that signaling of BDNF is involved in the mechanism of action of many drugs and that the BDNF protein could be a powerful drug. Knowledge about the regulatory mechanisms of BDNF gene could also lead to the development of drugs for treatment of patients suffering from these diseases. The project has had positive impact on the internationalization of R&D and higher education.

The role of the Norwegian partner in the project The role of the Norwegian partner in the project. What will the partnership achieve? Prof. Clive Bramham lab at University of Bergen possesses complementary high-level expertise and infrastructure as compared to Prof. Timmusk lab at Tallinn University of Technology, which covers a broad spectrum from molecular and cellular processes to assessment of synaptic plasticity and behavior of model animals. The coordinated application of this human capacity and methodological arsenal has facilitated integrative studies, leading to better understanding of the complexity of the brain. Prof. Clive Bramham lab was involved in many projects, particularly in electrophysiology and in vivo studies. Electrophysiology expertise is totally lacking in Estonian science and therefore this project has allowed Estonian scientists to learn methods of this important field of neuroscience. It is also expected, that members of Timmusk lab will carry out postdoctoral training in this field in Prof. Clive Bramham lab.

Publication 1 in Journal of Neurochemistry

Publication 2 in Journal of Neuroscience

Other publications   1. Nair RR, Patil S, Tiron A, Kanhema T, Panja D, Schiro L, Parobczak K, Wilczynski G, Bramham CR. Dynamic Arc SUMOylation and Selective Interaction with F-Actin-Binding Protein Drebrin A in LTP Consolidation In Vivo. Front Synaptic Neurosci. 2017 May 10;9:8. 2. Koppel I., Jaanson K., Klasche A., Tuvikene J., Tiirik T., Pärn A., Timmusk T. Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation. Glia, 2017, in press. 3. Nikolaienko O, Eriksen MS, Patil S, Bito H, Bramham CR. Stimulus-evoked ERK-dependent phosphorylation of activity-regulated cytoskeleton-associated protein (Arc) regulates its neuronal subcellular localization. Neuroscience. 2017 Sep 30;360:68-80.