Distribution
of the HD protein, Huntingtin, does not explain selective neuronal
vulnerability
Pattern
of Cell Loss:
atrophy
begins in tail of caudate
atrophy
gradually spreads toward head of caudate
atrophy
within the caudate head spreads from dorsal medial surface, laterally
and ventrally
most
medial and ventral structures (nucleus accumbens) are spared
Brain
Weight:
basal
ganglia weight is approximately 50 grams
brain
weight loss in HD is several hundred grams
unclear
exactly which cortical cells and regions also atrophy
Striatal
Neuron Changes in HD:
Lost:
GABA
projection neurons
GABA/enkelaphlin
to the lateral globus pallidum (GP)
GABA/substance
P (SP) and dynorphin (DYN) to the medial GP and substantia nigra
pars reticulata
Relatively
Spared:
large
acetylcholine (Ach) interneurons
GABA
interneurons
somatostatin
(SS)/neuropeptide Y (NPY) neurons which also contain nitric oxide
Pathological
Correlates to Clinical Characteristics
GABA
/ ENK > GABA / SP
Cell
loss in adult-onset HD
GABA
/ ENK = GABA / SP
Cell
loss in juvenile-onset HD
GABA
/ ENK projects to the lateral globus pallidum
Chorea
GABA
/ SP projects to the medial globus pallidum
Dystonia,
Rigidity
Wide
distribution and high expression of the HD protein in:
layer
4 of the occipital and temporal cortex
lateral
nucleus of the amygdala
dentate
gyrus of the hippocampus
The
presence of the HD protein alone does not cause the selective
vulnerability of neurons in the basal ganglia
Since
the presence of the HD protein alone does not cause the selective
vulnerability of neurons in the basal ganglia, there must be
other factos involved in cell loss
Current
research on mechanisms of energy depletion may determine what
other factors contribute to HD pathology
