Telomerase Promotes Survival of Neurons in Animal Studies
June 16, 2000; Westport, CT; (Reuters Health) -- TElomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase, is expressed at high levels in the developing rodent brain and may promote survival, while down-regulation of telomerase in adults makes neurons more susceptible to apoptosis. The findings are reported in the June 2nd issue of the Journal of Molecular Neuroscience.
Dr. Mark P. Mattson of the National Institutes on Aging in Baltimore, Maryland, and colleagues measured levels of TERT in the brains of embryonic, postnatal and adult rats, as well as embryonic cultured neurons. They found that TERT was readily detectable in the brains of embryonic and postnatal rats, as well as in embryonic cultured neurons from rats and mice, but was not detectable in adults.
Using an antisense oligonucleotide to suppress TERT expression in cultured neurons from mice, the researchers found that the cells were much more susceptible to apoptosis induced by trophic factor withdrawal, glutamate, iron sulfate, and staurosporine. Necrotic death did not differ significantly in oligonucleotide-treated cultures, "suggesting that TERT can suppress apoptosis, but not necrosis." They also did the reverse experiment, in which they generated cells expressing high levels of the TERT protein and telomerase activity, and found that the cells were more resistant to apoptosis after withdrawal of neurotrophic factors.
The resistance to apoptosis appeared to be due to a reduced decrease in mitochondrial transmembrane potential, an increase in the levels of mitochondrial reactive oxygen species, and a smaller increase in caspase activity in cells overexpressing TERT compared with control clones. "Collectively, these data indicate that TERT suppresses apoptosis at a relatively early stage, prior to mitochondrial dysfunction and caspase activation," Dr. Mattson's group writes.
"Whereas TERT may serve an antiapoptotic function in neurons during brain development, lack of TERT and telomerase activity in neurons in the mature brain may contribute to their death in a variety of neurodegenerative conditions," they add. "Our demonstration of an antiapoptotic function of TERT in neurons suggests that it will be of considerable interest to determine whether increasing TERT expression in neurons in the adult brain will protect them from degeneration."
Journal of Molecular Neuroscience , Vol. 14 (June 2, 2000)