Gangliosides (GA) are highly concentrated in the brain, particularly in the gray matter of the cerebral cortex. They carry most of the sialic acid in the central nervous system and play important roles in neural development, neuronal growth, message transmission between neurons, and myelination of neurons. Abnormal metabolism of sphingolipids like GA can cause several neurological disorders characterized by mental retardation and neurological deficits. The lipid content of myelin is much higher than that of gray and white matter, with more cerebrosides and cholesterol. GA levels increase with brain development and are thought to be important for optimal neuronal function.

1. Brain Lipids
Dr. Geeta Jaiswal

2. Gangliosides (GA)of the Brain
The brain and central nervous
system (CNS) contains
considerable levels of GA
In infancy (10% of the total lipid
mass of the brain is GA).
GA also carry the majority of
the sialic acid within the CNS.

3.  Within the CNS, Gangliosides(GA)
are found in the highest
concentrations in the Cerebral
Cortex of the brain’s Grey Matter
 (15 times that of other organs such
as the liver, lungs and spleen).
 3 times more GA in Grey Matter
than White Matter.
 The Grey Matter is responsible for
higher thought, learning and
memory

4. Functions of Gangliosides in
brain
 Gangliosides: are components of
the central nervous system,
including the brain.
 Gangliosides: are components of
brain neurons.
 Gangliosides carry most of the
Sialic acid within the brain.
 GA are naturally found in breast
milk, and therefore thought to be
important for optimal development

5.  GA are highly concentrated in the
brain, where they may play a role
in assisting in important neuronal
functions.
 Brain development/growth is
associated with an increase in brain
Gangliosides concentration
 GA are thought to play an
important role in intestinal
immunity development in the
neonate

6. In Neural development
 As already mentioned, studies have
shown that dietary GA are able to be
taken up by the body and incorporated
into the brain in the same way as GA
that are formed within the body.
 i.e. the content of GA in the developing
retina increases rapidly with increasing
dietary GA intake; the same has been
found for nerve cells.
 Brain GA is found within nerve cells in
Grey Matter, and are therefore thought
to assist in the important functions of

7. 2. Neuronal growth & message
transmission
 GA are required for normal axonal and dendritic
(projections from the neuron) development and growth
within neurons.
 As they increase the number of neurons they therefore
are also involved in synapse (space between neurons)
formation.

8.  A lack of sufficient gangliosides has
been shown to result in a striking
loss of new axons and dendrites.
 GA are also thought to be important
for message transmission by
controlling neurotransmitter release.
 Neurotransmitters are required to
keep the signals going (i.e. to jump
the ‘gaps’ between neurons).
 As neurons successfully fire, one to
the next, they create a circuit that
can process new information.

9. An example of a type of GA: GM1

10. Myelination
Gangliosides play
important
functions in
myelination of the
central and
peripheral nervous

11. Myelination is important
for……..1. The major function of myelin membranes
in the brain is to insulate axons (the body
of the neuron) and provide high
conductivity of messages within the brain,
essentially allowing the message to travel
faster.
2. High conductivity is important for
neuronal communication, which is
essential for brain functions.
3. Myelin insulates the axon and helps the
message travel faster between neurons –
ultimately resulting in faster

12. nucleus of Schwann cell
cytoplasm of axon The cell membranes
are compressed
together to form a
tightly packed layer of
myelin which is rich in a
particular type of
membrane
 It acts as an insulator
to prevent the
movement of ions
across the cell
membrane and so acts
as an insulator which
speeds up the speed of
transmission of nerve
impulses

13. Many neurones also have a myelin sheath around the axon – called
myelinated neurones.It is formed by specialised cells called Schwann
cells which wrap around the axon

14. Myelin: Insulating the neuron

16. Myelin sheath
Bundle of nerve fibres
Connective tissue coat of nerve
TS of Nerve

17. What is the function of myelin
sheath?
 Myelin sheath makes the conduction
of nerve impulse faster by
SALTATORY CONDUCTION.
 In this type of conduction the
impulse jumps through the NODES
OF RANVIER and so the chances of
leakage is also minimized.

18. WHITE AND GREY MATTER
OF BRAIN
The central nervous system is
composed of white matter and
gray matter.
White matter is so named
because the density of lipid-rich
myelinated axons gives the tissue
a white appearance.
Grey matter contains perikaryons
(less lipid) and appears darker.

19. The grey and
white matter is
easily identified
in this image

20. Brain
Red and green
arrows indicate
grey matter
layers
white matter

21. Are lipids the source of energy in
nervous tissue?
 No lipids do not provide energy to the
brain cells or nervous tissue as BETA
OXIDATION of fatty acids do not take
place in nervous tissue.
 So how the neurons get
energy???????
 They gets the energy from the ketone
bodies that is b-hydroxybutyric acid
acetoacetic acids and branched chain
amino acid like VALINE in case of
starvation.

22. Disorders Associated with Abnormal Sphingolipid Metabolism
Disorder Enzyme Deficiency Accumulating Substance Salient Features
Tay-Sachs
disease
Hexoseaminidase A GM2 ganglioside
Incidence 1 in 6000 births .infantile form:
rapidly progressing mental retardation,
blindness, early mortality 3 -4 yrs
Sandhoff
disease
HexoseaminidaseA
and B
Globoside
Infantile form- Neurological deficit and
mental retardations.Same Symptoms as
Tay Sachs
Tay-Sachs AB
variant
GM2 activator
deficiency
GM2 activator
(GM2A)
GM2 ganglioside
infantile form: same symptoms as Tay-
Sachs
Gaucher
disease
Acid β-glucosidase
(glucocerebrosidase)
Glucocerebrosides
hepatosplenomegaly, mental retardation in
infantile form, long bone degeneration
Fabry disease α-galactosidase A Ceramide trihexosesides Kidney failure, skin rashes. Death by 5 yrs
Niemann-Pick
diseases
Types A and B
Type C
sphingomyelinase
NPC1 protein
sphingomyelins
LDL-derived cholesterol
type A is severe disorder with
heptosplenomegaly, severe neurological
involvement leading to early death, type B
only visceral involvement

23. Krabbe disease;
globoid cell
leukodystrophy
(GLD)
galactocerebrosidase galactocerebrosides
mental retardation,
myelin deficiency
GM1gangliosidosis β-galactosidase-1 GM1 gangliosides
mental retardation,
skeletal
abnormalities,
hepatomegaly
Metachromatic
leukodystrophy;
sulfatide lipodosis
arylsulfatase A sulfatides
mental retardation,
metachromasia of
nerves
Fucosidosis α-fucosidase
pentahexosylfucoglyc
olipid
cerebral
degeneration,
thickened skin,
muscle spasticity
Farber
lipogranulomatosis
acid ceramidase ceramides
hepatosplenomegaly,
painful swollen joints
Disorder
Enzyme
Deficiency
Accumulating
Substance
Symptoms

24. Lipid Content of Grey and White Matter
 Grey matter, white matter, and
myelin were isolated from the frontal
lobes of humans aged 10 months, 6
yr, 9 yr, and 55 yr and the lipid
compositions of each were
determined.
 Myelin had a much higher lipid
content (78-81% of the dry weight)
than white matter (49-66%) or grey
matter (36-40%).

25. Myelin Content
 Myelin contained much higher molar
percentages of cerebroside and
cerebroside sulfate
 Slightly higher molar percentages of
cholesterol, and lower molar
percentages of ethanolamine
glycerophosphatides and choline
glycerophosphatides than grey matter.
 The molar percentages of serine
glycerophosphatides and sphingomyelin
were about the same in each tissue.

26. The Aldehyde content of
Glycerophosphatides
 Expressed as molar percentage of
the total lipoidal residues in each
lipid, were as follows:
 Ethanolamine glycerophosphatides
from myelin 40-50%;
 Ethanolamine glycerophosphatides
from grey matter 21-27%;

27.  serine glycerophosphatides from
myelin 21-36%;
 serine glycerophosphatides from grey
matter 0.3-3.8%.
 Choline glycerophosphatides from
either tissue contained only traces of
aldehydes.
 The extra-myelin portion of white matter
had a lipid composition that was very
similar to that of myelin, but quite
different from that of grey matter.

28. THANK YOU