Brain
This organ is composed of 10^11-12 neurons with 10^14 synapses. It has a high respiratory rate (20% of total O2 consumption) but only takes up 2% of the adult body mass. This energy is primarily derived from glucose, but, in starving conditions, can be ke
Glucose
This is the primary fuel source of the brain in normal conditions.
Aspartate (300x) and Glutamate (150x)
These amino acids have higher concentration in the brain than in blood plasma because they serve as neutrotransmitters in addition to protein synthesis.
GABA
This is the chief inhibitory neurotransmitter in the CNS. It plays a role in regulating neuronal excitability throughout the nervous system especially in controlling muscle tone.
Myelin
Glycerolipids and sphingolipids are much more common in the CNS (10-12%) than in the blood (5%) because of the presence of this structure.
Glycerolipid
Structure
: glycerol base + Acyl groups (1, 2 position) + Polar head group (3 position)
Most common in brain: Phosphatidylethanolamine, Phosphatidylcholine, Phosphatidylserine
Sphingolipid
These lipids are imp, esp in brain where they're abundant. Structural component of cellular membranes.
Structure
: Base= sphingosine (long chain, N-containing; -OH groups); Ampiphatic: polar head group + 2 nonpolar fatty acyl tails
Types
: Sphingophosphol
Sphingophospholipids
This lipid group includes the
Sphingomyelins
, which are most prevalent in brain; enriched in myelin.
Sphingoglycolipids
This lipid group has sugar/carb attached
o Cerebrosides
- glucocerebroside ()
- galactocerebroside ()
Glucocerebroside
This sphingoglycolipid is a precursor of globosides and gangliosides.
Galactocerebroside
This cerebroside is a common component of brain lipids; precursor of sulfatides.
Globoside
This type of sphingolipid is derived from glucocerebroside. It includes the addition of neutrally charged sugars.
Ganglioside
This type of sphingolipid is derived from glucocerebroside. It includes the addition of negatively charged sugars.
Ceremide
This molecule is a fundamental backbone structure within sphingophospholipid and sphingoglycolipids
Storage disease
This type of disease can include disorders in BREAKDOWN of sphingolipids. Once you've synthesized sphingolipids, they go through normal turnover. This type of disease is caused by a defect in an enzyme that facilitates this turnover/breakdown.
Tay-Sachs Disease
#1
: This is a sphingolipid storage disease:
Symptom
: Blindness, MR,
muscles weak, death at ages 3-5.
Sph, Lip Accumulating
: Ganglioside GM2 (accumulates in cells including nerve cells in brain, especially in early brain development)
Enzyme Deficiency
:
Gaucher's Disease
#2
: This is a sphingolipid storage disease:
Symptom
: Type I,II, III have Liver & spleen enlarge, MR; Type II and III have neurological symptoms -> brain damage.
Sph, Lip Accumulating
: Glucocerebroside (accumulate in lyosomes, esp in macrophages)
Enzyme
Krabbe's Disease
#4
: This is a sphingolipid storage disease:
Symptom
: demyelination,
MR; cause of leukodystrophy (imperfect myelin); death by age 2
Sph, Lip Accumulating
: Galactocerebroside
Enzyme Deficiency
: b-galactocerebrosidase
treatment
: none effective
Neimann-Pick Disease
#3
: This is a sphingolipid storage disease:
Symptom
: MR, liver and
spleen enlarge
Sph, Lip Accumulating
: Cer-phosphochole (sphingomyelin) -Types A (infantile) has <1% activity -> liver enlargement and brain damage; Type B has 10% activity -> live longe
Neuron
This is a specialized cell that functions to receive, conduct, and transmit signals.
Body (soma)
This part of the neuron is defined by the presence of:
- PM controls movement of ions
- nucleus and nucleolous
- Ribosomes (free and membrane-bound/rER; Nissl substance)
- Golgi-package secretory proteins
- Endosomes/Lysosomes
- Mitochondria (need lots of
Axon
This part of the neuron is defined by the presence of neurofilaments; extensive crosslinks; NO protein synthesis
Dendrite
This part of the neuron is defined by the presence of protein synthesis and active ribosomes (base of spines).
Microtubules
Polymeric arrangement of tubulin subunits; 25nm diameter
ALL parts of neurons
MAPs: ex. tau protein (Alzheimers)
TRACKS for axonal transport
Neurofilaments
Intermediate filaments; 10nm diameter
Major cytoskeletal element in axon; Form extensive crosslinks
Polypeptide subunits: NF-H; NF-M; NF-L
Note: In Glia, GFAT is a cytoskeletal structure that does NOT have extensive cross-links.
Microfilaments
Actin filaments; 5-9nm
Found predominantly at leading edge of growth cones, presynaptic terminals, and just under plasma membrane
Aterograde
Red
: This type of axonal transport moves from the
soma ? terminal
via
kinesin
n*. It includes fast transport (50-400 mm/day) of vesicles, mitochondria, and slow transport (.2-8 mm/day) of cytosolic protein, cytoskeletal elements.
Retrograde
Blue
: This type of axonal transport moves from the
terminal ? soma
via
dynein
in
only fast transport
t* (50-400 mm/day) that recycles endosomes.
Electrical Synapse (gap junctions)
� Allows direct electrical coupling
� Most rapid form of transmission
� Bi-directional
� Connexons forming channels between 2 cells; 35Ang or 3.5nm
Chemical Synapse
� Transmit electrical signal INDIRECTLY
� 1 direction only
� sends mediator from pre- to post-synaptic cell
� slower
Glial cell
� Physical support for neurons
� Produce neurotrophic factors
� Direct migrating neurons to correct targets
� Produce myelin
� Serve as brain's immune cells
� Clean up synapse; maintain neuronal signaling capacity
� Participate in BBB
� Communicate: some
CNS Glial cell
This group of cells includes:
Oligodendrocytes
(form myelin)
Microglia
(brain "immune" cells)
Ependymal cell
(line ventricles, circulate CSF w/ cilia)
Astrocytes
(most plentiful and diverse CNS glial cell; development, BBB, maintain synaptic env, communic
PNS glial cell
This group of cells includes:
Schwann cells
(form myelin, but not all myelinate)
Astrocyte
This type of CNS glial cell has end feet that surround brain capillaries & induce tight junctions between endothelial cells, preventing free movement. It functions to help create the blood brain barrier.
Blood Brain Barrier
This restriction stops many blood substrates from crossing into the brain. It is made in part by collaboration between astrocytes and endothelial cells.
What can pass through:
� Lipophilic compounds (<500 Daltons)
� Stuff that has transporters (glucose, A
Oligodendrocyte
This cell type is a CNS glial cell that mediates myelination of multiple axons in the CNS.
Schwann cell
This cell type is a PNS glial cell that mediates myelination of only one axon in the PNS.
Charco-Marie-Tooth Disease
Pathology
: Inherited neurological disorder of the
PNS
. Defined by slowly progressive degeneration of muscle movement in foot, lower leg, hands and forearms
� Genetic heterogeneity
� 1/2500 in US
Guillain-Barre Disorder
Pathology
: Acute inflammatory demyelinating disorder;
Autoimmune disorder of
PNS
� Weakness in legs and arms, often a few weeks after viral symptoms.
� 1/100,000
Prognosis
: Almost all pts recover completely after time on respirator
Multiple Sclerosis (MS)
Pathology
:Autoimmune disorder of
CNS
� Begins w/ visual impairments followed by muscle weakness
� Onset at 20-40 yrs, more common in females
� Often show remissions
Treatment
: steroids, interferons (Betaseron, Rebif or Avonex - ex. Avonex balances the e