TO BRIAN COLLINS:
RE: MODELS FOR PD
I AM NOT COMPLETELY CLEAR ON WHETHER THE
FOLLOWING SHEDS ANY LIGHT ON THE CREATION OF A
FEEDBACK CONTROL MODEL - IT ACTUALLY SEEMS TO
BEG THE QUESTION, WHY DO OVER-RESPONSIVE D2
RECEPTORS CAUSE TREMORS? ANYHOW:
SEE "MOTOR RESPONSE COMPLICATIONS AND THE
FUNCTION OF STRIATAL EFFERENT SYSTEMS,"
NEUROLOGY 1993: 43:S 23-27. . . . . ALSO REPORTED IN
PARKINSON'S DISEASE UPDATE, #57, 1995.
"AS PARKINSON'S DISEASE PROGRESSES, NERVE
CELLS IN THE SUBSTANTIA NIGRA CONTINUE TO
DISAPPEAR. . . . THE CELLS ARE NOT NUMEROUS
ENOUGH TO STORE DOPAMINE AND RELEASE IT
GRADUALLY . . . .GLIAL AND ENDOTHELIAL BRAIN
CELLS CONTRIBUTE TO THE PRODUCTION OF
DOPAMINE, BUT THEY CANNOT STORE DOPAMINE,
HENCE THE 'DUMPING' INTO THE SYNAPTIC CLEFT. . . "
[NORMALLY FOLLOWING RECEPTOR STIMULATION,
DOPAMINE IS PUMPED BACK INTO THE NERVE CELL
THAT CREATED IT. WHEN DOPAMINE PERSISTS IN THE
SYNAPTIC CLEFT IT LEADS TO HYPERACTIVITY]
"THERE ARE TWO MAJOR PATHWAYS FROM THE
STRIATUM TO THE INTERNAL GLOBUS PALLIDUS. . . .
THE DIRECT PATHWAY CONNECTS THE GP TO THE
STRIATUM BY MAINLY D1 RECEPTORS. . . . THE
INDIRECT PATHWAY CONNECTS THROUGH THE
EXTERNAL GP AND THE SUBTHALAMIC NUCLEUS. . . .
WITH PARKINSON'S THE D1 NEURONS ARE
UNDER-RESPONSIVE (BECAUSE OF LESS DOPAMINE),
BUT THE D2 NEURONS BECOME OVER-RESPONSIVE. . .
. . THE SUB.TH.NC. & INTERNAL GP BECOME
ABNORMALLY ACTIVATED. . . .SINCE THE GP ACTS LIKE
A BRAKE ON MOTOR ACTIVITY. . . .WITH PARKINSON'S
ITS LIKE TRYING TO DRIVE A CAR WITH THE PARKING
BRAKE ON. . . . PALLIDOTOMY PARTIALLY DESTROYS
THE BRAKE. . . . "
STEPHAN SCHWARTZ [log in to unmask]
