Y. Muller et al., THYROID-HORMONE PROMOTES BCL-2 EXPRESSION AND PREVENTS APOPTOSIS OF EARLY DIFFERENTIATING CEREBELLAR GRANULE NEURONS, International journal of developmental neuroscience, 13(8), 1995, pp. 871-885
Programmed cell death is a basic cellular process that has aroused muc
h interest in recent years. Like immune cells, cultures of cerebellar
granule neurons are very homogeneous and provide a unique opportunity
for quantifying by flow cytometry one form of programmed cell death in
the CNS, the apoptosis, and for studying its regulation by neurotroph
ic factors. We found that thyroid hormone promoted postmitotic surviva
l by preventing the apoptosis of newly formed and early differentiated
granule neurons in a dose-dependent manner. This regulation could be
through the protein bcl-2, which is known to prevent cell death. This
protein was present at ail stages of granule neuron differentiation an
d appeared to be developmentally regulated. It was underexpressed in a
poptotic granule neurons. The protein content of the cerebellum in hyp
othyroid rats was drastically reduced. In contrast, thyroid hormone ca
used a marked dose-dependent increase in the amounts of this protein i
n granule neuron cultures. The possibility that thyroid hormone may be
directly or indirectly required to promote cell survival is discussed
, in terms of the hormone control of the local delivery of neurotrophi
ns, such as NGF and NT-3, as well as the expression of their low affin
ity receptors, gp75. We suggest that thyroid hormone has a permissive
action on the developing CNS.