early brain development part two

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Early brain development part two DOMINA PETRIC, MD

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Early brain development part two

DOMINA PETRIC, MD

Growth cones

Growth cone has flat lamminar type of appearance: LAMELLA PODIUM (SHEET FLOOR).

FILOPODIA are processes that extend from the lamella podium.

Filopodia have dynamic behavior because they have ACTINS.

Growth cone is rich of mitochondria and it is very important for the axon development.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Growht cone

https://cmgm.stanford.edu

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Molecular signals for axon guidance

cell-associated molecules

diffusible molecules

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Cell-associated molecules

Those molecules are on the surface of cells or embedded in extracellular matrix.

They mediate molecular interactions between growth cones and parenchyma.

Interactions with growth cone can trigger second messenger systems in growth cones that transduce extracellular signals

into patterns of growth.

These molecules are important for stabilizing linkages between axons and glia.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Cell-associated molecules

integrins (extracellular matrix molecules)

calcium independent cell adhesion molecules (CAM) like NCAM and L1

calcium dependent cell adhesion molecules (CAM) like CADHERINS

EPHRINS and EPHRIN receptors play important role in establishing neural topography

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Diffusible molecules

Those molecules are secreted by target tissues.

They diffuse into extracellular fluids.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Diffusible molecules

• They affect growth and survival of neurons and their processes.

• TROPIC diffusible molecules guide growing axons toward or away from source.

• Tropic molecules can be chemo-attractant and chemo-repellant molecules.

• TROPHIC diffusible molecules promote survival and growth of neurons and their processes.

• In the peripheral nervous system trophic molecules match axonal innervation with target tissue.

• Production of trophic molecules is activity dependent.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Diffusible molecules can be

TROPIC: P like PATHWAY, guidance of growing axons towards or away from source.

TROPHIC: H like HEALTH, nourishment, survival and growth of neurons and their processes.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

CHEMOATTRACTION CHEMOREPULSION

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Tropic diffusible molecules

Chemo-attractanttropic molecules

Chemo-reppelanttropic molecules

Tropic diffusible molecules

NETRIN/SLIT family (netrin is chemo-attractant, slit antagonises netrin)

SEMAPHORINS (chemo-repellants)

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Trophic molecules (neurotrophins) and neurotrophin hypothesis

NEUROTROPHIN HYPOTHESIS: in development, the survival of neurons and their axonal connections

depends upon the availability of some minimal quantity of trophic factor.

Target tissues synthesize and secrete a limited quantity of trophic factor.

Survival of neuron and their specific connections depens upon successful competition among inputs for a

limited quantity of trophic factor.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Neurotrophins

In maturity, regulated secretion of trophic factors may help shape neuronal

connections in response to injury or adaptation to new patterns of neural activity.

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Neurotrophins

NERVE GROWTH FACTOR (NGF)

BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF)

NT-4/5, NT-3

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Neurotrophins

• Neurotrophin receptors are TIROSINE KINASE RECEPTORS (TRK).

Results of TRK receptors can be:

• cell survival

• neurite outgrowth and neuronal differentiation

• activity-dependent plasticity

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Neurotrophin receptor p75

p75

RhoA

Neurite growth

C-Jun

Cell death

NF-kB

Cell survival

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

Second messengers

Outcome

Literature

https://www.coursera.org/learn/medical-neuroscience/lecture: Leonard E. White, PhD, Duke University

https://cmgm.stanford.edu

HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY