Multipolar Neuron



Best Known Neurotransmitters

n   Acetylcholine (ACh)

n   Norepinephrine (NE)

n   Dopamine DA)

n   Serotonin or 5-Hydroxytryptamine (5HT)

n   GABA

n   Endorphin

Acetylcholine (ACh)

n   neurons using ACh are known as “cholinergic neurons”.  Examples:

n   motor neurons

n   parasympathetic neurons

n   many CNS neurons (in cortex, basal ganglia, hippocampus, brainstem)

n   acetylcholinesterase breaks down ACh

Norepinephrine (NE)

n   aka “noradrenaline”

n   transmitter of symnpathetic synapses to organs and glands

n   also found in many CNS neurons (RF, hypothalamus)

n   action terminated by reuptake

n   closely related to DA (“catecholamines”) and both related to 5HT (monoamines)


n   primarily known as a CNS transmitter

n   transmitter in basal ganglia, limbic system & frontal cortex & parts of hypothalamus that control pituitary

n   action terminated by reuptake

Serotonin (5HT)

n   primarily known as CNS transmitter

n   found in neurons of brainstem associated with sleep & pain suppression, & in limbic system

n   action terminated by reuptake


n   best known inhibitory transmitter

n   widely distributed in CNS

n   seems necessary to keep neuron activity “in check”

Neuromuscular Junction

Myasthenia Gravis: A Neuromuscular Disease

n   abnormal muscle fatiguibility & weakness

n   progressive, usually affects muscles of head 1st

n   autoimmune disease attacking ACh receptors on muscles


Patient Asked to Look Up


Ptosis (drooping of eyelid)

n   Maybe Sleepy had MG

MG Tests

n   Intravenous administration of Tensilon (edrophonium), a short-acting anti-cholinesterse, usually produces brief improvement

n   Nerve conduction studies show normal conduction; electromyogram shows normal muscle response which decreases with each response

n   Chest xray may show thymoma

MG Treatments

n   Decrease the attack by the immune system:

    immunosuppressant drugs


    plasma exchange to remove antibodies

n   Increase ACh levels with an anti-cholinesterase drug (prevents normal breakdown of ACh, prolonging it ability to stimulate remaining ACh receptors)

Botulinum Toxin

n   Toxin produced by bacteria Clostridium botulinum or its spores, incredibly potent, easily absorbed from GI tract, and then distributed by blood everywhere except CNS

n   Intereferes with the release of ACh, causing paralysis & autonomic effects

n   Selective injections of botulinum toxin now used to treat excess muscle contraction (spasticity)


Action of Botulinum Toxin

Black Widow Spider Venom

Neurons and Glia

Glial Cells (“supporting cells”)

n   5-10X more numerous than neurons

n   make up about half of brain weight

n   several distinct types

n   growing evidence of multiple roles that glia play

Astrocytes (most common)

n    separate synapses

n    form a “limiting membrane” on outside of CNS

n    surround CNS capillaries adding to blood-brain barrier

n     transfer materials to & from neurons

n    produce growth factors

n    clean up excitatory transmitter glutamate 

n    may even communicate?

n    can multiply to form scar tissue or tumors

Astroglia or Astrocyte


n   the other large glial type (“macroglia”)

n   form myelin sheaths on CNS neurons

n   form thin coat on unmyelinated ones

n   produce nerve growth factor

n   Schwann cell is the PNS counterpart





Myelin Sheaths

Cross-section of Nerve

Axons Within Nerve


n   small glia which are mobile phagocytes

n   Recent evidence suggests they play a key role in neurodegenerative diseases - “activated” microglia may attack neurons in AIDS, Alzheimer’s, MS, etc.

n   contribute to scar tissue formation

Ependymal Cells

n   line the ventricles/canals

n   participate in CSF production

n   have cilia to help circulate CSF

n   may transport materials between CSF & neurons

Glia Clinical Notes

n   60% of brain tumors are gliomas

n   multiplying of glia to form scar tissue (“gliosis”) can irritate nearby neurons: important cause of focal epilepsies

Multiple Sclerosis: Another Autoimmune Disease

n    Immune system attacks miscellaneous myelin sheaths in CNS, causing demyelination in 250,000 in US (2/3  are women)

n    Where myelin is lost, hard plaques of scar tissue (glia & immune cells) form

n    Symptoms depend on which neurons lose myelin but always multiple symptoms (clinically diagnosed)

n    Periodic attacks (days) & then remissions (months) which progress

Loss of White Matter in MS

Demyelination Seen in MRI

What Causes MS?

n   More common in northern climates

n   For some reason B-cells attack oligodendrocytes, T-cells attack certain myelin proteins that resemble a virus.

n   Illness activating immune system can aggravate the disease

n   Less common in Blacks, Asians, Native Americans and shows some tendency to run in families (role of genetics). Identical twins have 30% concordance.



MS Treatment Approaches

n   Avoid stress & illness; treat the specific symptoms

n    Steroids & other immunosuppressant drugs to shorten attacks

n   New meds: beta-interferon, methotrexate

Consider this:

n    You’ve recently had the flu or some other infection (60%), or you’ve had a vaccination. You notice some tingling & numbness in your feet & your legs seem to be getting weaker (60% can’t walk). Over a period of hours (or up to 2 weeks) the weakness & loss of ability to move moves up your body. If it gets high enough you may not be able to breathe (20-30%) swallow, or speak & may have bilateral facial paralysis. 5% die

Guillain-Barre Syndrome

n   Rapid ascending, usually symmetrical PNS demyelination

n   Loss of motor function most obvious; some numbness & back pain possible

n   Can be a medical emergency- 25% need artificial respiration

n   Probably a temporary autoimmune disorder; majority have recently had an infection or vaccination

n   Some begin recovery within weeks, others months. 70-80% full recovery



Brain Tumors or Neoplasms

n    Usually due to abnormal growth of tissues /cells other than neurons

     ~15-20% Meningiomas - benign, encapsulated  growth of meninges

     ~60% Gliomas - infiltating, usually malignant multiplication of glial cells

   Most common – astrocytoma

   Most dangerous – glioblastoma multiforme

   Acoustic Schwannoma/neuroma - covering on 8th cranial nerve grows

     ~10-30% metastatic tumors (originate outside the brain, e.g. in lungs, breasts)

Brain Tumors continued

n   Most tumors occurring in adulthood are “supratentorial” (in cerebral hemispheres)

n   Most tumors in children are “infratentorial” (below tentorium, in brainstem). The single most common is a medulloblastoma.

n   Tumor problems: compression of brain area, infiltration, increased ICP, sometimes may impair CSF flow or endocrine controls.


n    Can be caused by bacteria, virus, fungus, or reaction to medications

n    Headache, fever, irritability, stiff neck, photophobia, nausea, possible seizures or altered cognition

n    Bacterial meningitis can progress very rapidly so is a medical emergency

n    Viral meningitis is generally less serious

n    Inflammation/swelling can lead to lasting deficits in 20-30% (impaired hearing, retardation, epilepsy)


n   Lumbar puncture to identify infection

n   Kernig’s sign

n   Brudzinki’s sign

Some Other CNS Infections

n   Viral

    May be pantropic (general infections of many tissues like mumps or herpes) or neurotropic (specific affinity for nerves).

    Example: viral encephalitis – many varieties (St. Louis, Equine, HIV) – virus spreads to brain itself with high risk of mortality or disability

    Common forms spread from animals to humans by mosquitos

Rabies – a neurotropic infection

n   Virus is picked up by nerve endings at the site of the bite & slowly(2 weeks-6 months) travels to CNS via retrograde transport. If the virus reaches the CNS before vaccination it is invariably fatal.

n   Symptoms may appear in 2 forms: “furious rabies” - hyperexcitable, irritable, muscle pain and spasms, may viciously bite at anything, or “dumb rabies” - lethargy progessing to paralysis & coma

Creutzfeldt-Jakob Disease

n   Progressive dementia and cerebellar ataxia

n   In past most cases caused by exposure to tissue (cornea or dura transplants, human growth hormone injections, contamination from previous brain surgery on infected patient). A few (5-10%) cases are familial

n   Long incubation period

n   Caused by tiny abnormal proteins (prions) which are very resistant to inactivation

Bovine Spongiform Encephalopathy (BSE)

n   Related animal diseases transmitted even through eating feed containing tissue from infected  (“mad cow disease”)

n   1996 – evidence that BSE could cause a type of CJD in humans

n   1/2001 – FDA recommends banning blood donations from those who lived in BSEcountries



n   BSE identified in these countries



Fungal (most often Candida albicans)

n   Usually in immune-compromised individuals

Infections continued

n    Parasitic Bacterial Infections


     Lyme Disease (from ticks)- untreated can cause arthritis and neurological problems like

               Bell's palsy - facial muscle droop



               tingling of extremities

               trouble with concentration *

               memory loss *

               extreme fatigue *



Tick Bite

Bull’s Eye Rash