Neurotrophic factors
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This document discusses neurotrophic factors, which are growth factors that influence neuron proliferation, differentiation, survival, and death. The neurotrophic factor hypothesis proposes that neurons require specific neurotrophic factors for survival, and neurons without adequate access to these factors die by apoptosis. The major neurotrophins discussed are NGF, BDNF, NT-3, and NT-4, which bind to specific receptors on neurons. Neurotrophins are involved in cell survival, proliferation, differentiation, learning and memory, and synaptic plasticity. Reduced levels of BDNF in mice lead to abnormal behavior and early death. BDNF levels are also reduced in neurodegenerative diseases. New strategies for delivering neurotrophins in a
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1). The reticular formation is an ill-defined region in the brainstem comprising neurons and fibers that extends from the spinal cord to the thalamus. It is involved in arousal, attention, sleep-wake cycles, and autonomic functions.
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Neurotransmitters are chemical messengers that transmit signals between neurons. The document discusses the history and criteria for classifying a substance as a neurotransmitter. Neurotransmitters are classified based on their chemical nature as amino acids, amines, or others. They are also classified based on their function as either excitatory or inhibitory. The document describes examples from each group and where they are secreted in the body. It further explains the processes of transport, release, inactivation, and reuptake of neurotransmitters at the synapse.
Adult Neurogenesis
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Neurotrophic factors
- 2. Introduction Neurotrophic factors are a unique family of growth factors that influence the proliferation, differentiation, survival, and death of neuron and non-neuronal cells. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 as a family implies also mediate high-order activities, such as learning, memory, and behavior, along with cell survival.
- 3. Neurotrophic Factor Hypothesis Neurotrophic Factor Hypothesis was first formulated by Viktor Hamburger, Rita Levi-Montalcini and their colleagues in 1940s. Cells of developing neurons produce only a limited amount of a neurotrophic factor, that is taken up by the nerve terminals. Neurotrophic factors bind to specific receptors and are transported to the neuronal cell, where they promote neuronal survival. Neurons without access to adequate amounts of these factors die by apoptosis.
- 4. Neurotrophins isolated are : Nerve growth factor (NGF) Trk A brain-derived neurotrophic factor (BDNF) Trk B NT-3 Trk C NT - 4/5 Trk B (trk = tyrosine kinase ) Receptor
- 6. Functions of Neurotrophins : ● Cell survival ● Proliferation ● Differentiation ● Migration of interneurons ● Development ● Learning and memory ● Synaptic plasticity (ability of synapses to strengthen or weaken depending upon their act.)
- 7. Localisation of Neurotrophins They are present in many regions of CNS including the : ● Hippocampus ● Cerebral cortex ● Cerebellum ● Hypothalamus ● Substantia nigra ● Amygdala ● Spinal cord
- 8. Neurotrophins and Behavior These experiments were done on a BDNF+/- mice. Mice in which BDNF levels are reduced by approximately one-half, showed abnormal behaviour In the absence of normal levels of BDNF, mice exhibit enhanced aggressiveness, hyperactivity. It was also a cause for early postnatal death
- 9. Why that happened ? 1. BDNF encourages neurogenesis in several parts of the rat brain, such as thalamus, and hypothalamus 2. It increases the number of granule cells 3. In the absence of it, there was impaired development of the layers of the cerebellar cortex 4. Hence it dies because BNDF is crucial to Prenatal development + postnatal survival (i.e. memory & brain functioning)
- 10. BDNF and neurodegenerative diseases ● Selective reduction of BDNF in the hippocampus has been reported in Alzheimer’s disease ● Decreased BDNF protein has been demonstrated in Parkinson’s disease ● Recent work has implicated BDNF in Huntington’s disease as well ● In addition to its role in pre natal development, BDNF is also important post natally functioning in memory formation, survival of adult NPCs 23
- 11. Introduction of artificial neurotrophins First, it has become clear that the physical delivery of sufficient quantities of neurotransmitters is a major obstacle. Second, because neurotrophins have multiple effects on neuronal activity, indiscriminate “flooding” of the CNS with neurotrophic factors will likely lead to side effects such as abnormal behaviour SO new strategies are introduced which include more regulated application of neurotrophins through stereotactic injection
- 12. References.. ● https://www.sacklerinstitute.org/cornell/CBGB/publications/Lee,%20Chao%20(in% 20press).pdf ● https://www.slideshare.net/theanatomist/role-of-brain-derived-neurotrophic-factor- bdnf-in-neurodevelopment ● https://en.wikipedia.org/wiki/Neurotrophic_factors ● www.umich.edu