Limits...
Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.

Eitan E, Tichon A, Gazit A, Gitler D, Slavin S, Priel E - EMBO Mol Med (2012)

Bottom Line: Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents.The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated.Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Show MeSH

Related in: MedlinePlus

Attenuation of motor neuron loss by AGS-499 treatment in the lumbar SC of SOD1 Tg miceA,B. Photomicrographs of Nissl-stained sections derived from the ventral horn of the lumbar SC from untreated mice at the age of 70 days, vehicle-treated and AGS-499-treated mice at the age of 100 days.C. Quantification of number of motor neurons per section was performed by counting motor neurons from serial micrographs (n = 10 from each animal) taken from the T10-L5. The results are shown as mean ± s.e.m.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3376858&req=5

fig07: Attenuation of motor neuron loss by AGS-499 treatment in the lumbar SC of SOD1 Tg miceA,B. Photomicrographs of Nissl-stained sections derived from the ventral horn of the lumbar SC from untreated mice at the age of 70 days, vehicle-treated and AGS-499-treated mice at the age of 100 days.C. Quantification of number of motor neurons per section was performed by counting motor neurons from serial micrographs (n = 10 from each animal) taken from the T10-L5. The results are shown as mean ± s.e.m.

Mentions: Motor neuron survival was assessed morphologically by Nissl staining of lumbar SC sections (L5-T10; Fig 7A) derived from SOD1 Tg mice at the age of 100 days, treated with vehicle or AGS-499 (6 mg/kg) starting at 70 days of age. Similar sections derived from untreated SOD1 Tg mouse at 70 days of age were also examined for assessing the number of motor neurons prior the beginning of the treatment. The representative micrographs in Fig 7B show that a significant loss in motor neurons in the lumbar SC is observed at the age of 100 days as compared to the pre-symptomatic stage of 70 days. At the age of 100 days, a substantial attenuation in motor neuron loss in the AGS-499-treated mice was observed as compared to the vehicle-treated mice. Counting the number of motor neurons in 10 sections from each animal revealed that the mean number of motor neurons per section in vehicle-treated animals was 26.7 ± 1.96 and 43.6 ± 4.26 in AGS-499-treated mice, an increase of 60% in motor neuron survival (Fig 7C).


Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.

Eitan E, Tichon A, Gazit A, Gitler D, Slavin S, Priel E - EMBO Mol Med (2012)

Attenuation of motor neuron loss by AGS-499 treatment in the lumbar SC of SOD1 Tg miceA,B. Photomicrographs of Nissl-stained sections derived from the ventral horn of the lumbar SC from untreated mice at the age of 70 days, vehicle-treated and AGS-499-treated mice at the age of 100 days.C. Quantification of number of motor neurons per section was performed by counting motor neurons from serial micrographs (n = 10 from each animal) taken from the T10-L5. The results are shown as mean ± s.e.m.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376858&req=5

fig07: Attenuation of motor neuron loss by AGS-499 treatment in the lumbar SC of SOD1 Tg miceA,B. Photomicrographs of Nissl-stained sections derived from the ventral horn of the lumbar SC from untreated mice at the age of 70 days, vehicle-treated and AGS-499-treated mice at the age of 100 days.C. Quantification of number of motor neurons per section was performed by counting motor neurons from serial micrographs (n = 10 from each animal) taken from the T10-L5. The results are shown as mean ± s.e.m.
Mentions: Motor neuron survival was assessed morphologically by Nissl staining of lumbar SC sections (L5-T10; Fig 7A) derived from SOD1 Tg mice at the age of 100 days, treated with vehicle or AGS-499 (6 mg/kg) starting at 70 days of age. Similar sections derived from untreated SOD1 Tg mouse at 70 days of age were also examined for assessing the number of motor neurons prior the beginning of the treatment. The representative micrographs in Fig 7B show that a significant loss in motor neurons in the lumbar SC is observed at the age of 100 days as compared to the pre-symptomatic stage of 70 days. At the age of 100 days, a substantial attenuation in motor neuron loss in the AGS-499-treated mice was observed as compared to the vehicle-treated mice. Counting the number of motor neurons in 10 sections from each animal revealed that the mean number of motor neurons per section in vehicle-treated animals was 26.7 ± 1.96 and 43.6 ± 4.26 in AGS-499-treated mice, an increase of 60% in motor neuron survival (Fig 7C).

Bottom Line: Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents.The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated.Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Show MeSH
Related in: MedlinePlus