Neural progenitor cells existing in the developing and adult brain retain the capacity
to self renew and to produce the major cell types of the brain opening new strategies
for restorative therapy of neuropsychiatric disorders. These cells can be grown in
vitro while retaining the potential to differentiate into nervous tissue. A primary
target for neurorestoration is Parkinson's disease, characterized by a continuous
loss of the dopaminergic neurons in the substantia nigra pars compacta leading to
dopamine depletion in the striatum and subsequent clinical symptoms including bradykinesia,
rigidity and tremor. We established a protocol for isolation, long-term expansion
and dopaminergic differentiation of rodent and human mesencephalic neural progenitor
cells. Here we perform functional studies using electrophysiological techniques on
midbrain neurons derived from rodent mesencephalic progenitor cells. We could show
that these cells express A-type currents as well as TEA-sensitive delayed rectifier
potassium channels as well as ttx-sensitive sodium currents, and fire action potentials.
Furthermore, we detect a slowly activating hyperpolarization-activated inward cation
current (Ih), which is specific for dopaminergic neurons among present midbrain neurons.
Finally, we measured the response to various concentrations of GABA, glutamate or
N-methyl-D-aspartate. The characteristics of GABA-induced currents were typical for
GABAA receptors. Nine out of 10 cells expressing glutamate-induced currents also showed
functional NMDA receptors with amplitudes of approx. 27% of the mean glutamate amplitude.
Our results demonstrate that differentiated mesencephalic progenitors exhibit some
major morphological and functional characteristics of dopaminergic neurons. Therefore,
these neural progenitor cells might be suitable for regenerative therapeutic approaches
in Parkinson's disease.
