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

1. 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