Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice

Kim A. Staats, Lawrence Van Helleputte, Ashley R. Jones, André Bento-Abreu, Annelies Van Hoecke, Aleksey Shatunov, Claire Simpson, Robin Lemmens, Tom Jaspers, Kiyoko Fukami, Yoshikazu Nakamura, Robert H. Brown, Philip Van Damme, Adrian Liston, Wim Robberecht, Ammar Al-Chalabi, Ludo Van Den Bosch

Research output: Contribution to journalArticle

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Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease, resulting in selective motor neuron degeneration and paralysis. Patients die approximately 3-5years after diagnosis. Disease pathophysiology is multifactorial, including excitotoxicity, but is not yet fully understood. Genetic analysis has proven fruitful in the past to further understand genes modulating the disease and increase knowledge of disease mechanisms. Here, we revisit a previously performed microsatellite analysis in ALS and focus on another hit, PLCD1, encoding phospholipase C delta 1 (PLCδ1), to investigate its role in ALS. PLCδ1 may contribute to excitotoxicity as it increases inositol 1,4,5-trisphosphate (IP3) formation, which releases calcium from the endoplasmic reticulum through IP3 receptors. We find that expression of PLCδ1 is increased in ALS mouse spinal cord and in neurons from ALS mice. Furthermore, genetic ablation of this protein in ALS mice significantly increases survival, but does not affect astrogliosis, microgliosis, aggregation or the amount of motor neurons at end stage compared to ALS mice with PLCδ1. Interestingly, genetic ablation of PLCδ1 prevents nuclear shrinkage of motor neurons in ALS mice at end stage. These results indicate that PLCD1 contributes to ALS and that PLCδ1 may be a new target for future studies.

Original languageEnglish (US)
Pages (from-to)11-17
Number of pages7
JournalNeurobiology of Disease
Volume60
DOIs
StatePublished - Dec 1 2013

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Phospholipase C delta
Amyotrophic Lateral Sclerosis
Survival
Motor Neurons
Inositol 1,4,5-Trisphosphate Receptors
Nerve Degeneration
Inositol 1,4,5-Trisphosphate
Paralysis
Endoplasmic Reticulum
Neurodegenerative Diseases
Microsatellite Repeats
Spinal Cord

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

Staats, K. A., Van Helleputte, L., Jones, A. R., Bento-Abreu, A., Van Hoecke, A., Shatunov, A., ... Van Den Bosch, L. (2013). Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice. Neurobiology of Disease, 60, 11-17. https://doi.org/10.1016/j.nbd.2013.08.006

Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice. / Staats, Kim A.; Van Helleputte, Lawrence; Jones, Ashley R.; Bento-Abreu, André; Van Hoecke, Annelies; Shatunov, Aleksey; Simpson, Claire; Lemmens, Robin; Jaspers, Tom; Fukami, Kiyoko; Nakamura, Yoshikazu; Brown, Robert H.; Van Damme, Philip; Liston, Adrian; Robberecht, Wim; Al-Chalabi, Ammar; Van Den Bosch, Ludo.

In: Neurobiology of Disease, Vol. 60, 01.12.2013, p. 11-17.

Research output: Contribution to journalArticle

Staats, KA, Van Helleputte, L, Jones, AR, Bento-Abreu, A, Van Hoecke, A, Shatunov, A, Simpson, C, Lemmens, R, Jaspers, T, Fukami, K, Nakamura, Y, Brown, RH, Van Damme, P, Liston, A, Robberecht, W, Al-Chalabi, A & Van Den Bosch, L 2013, 'Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice', Neurobiology of Disease, vol. 60, pp. 11-17. https://doi.org/10.1016/j.nbd.2013.08.006
Staats KA, Van Helleputte L, Jones AR, Bento-Abreu A, Van Hoecke A, Shatunov A et al. Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice. Neurobiology of Disease. 2013 Dec 1;60:11-17. https://doi.org/10.1016/j.nbd.2013.08.006
Staats, Kim A. ; Van Helleputte, Lawrence ; Jones, Ashley R. ; Bento-Abreu, André ; Van Hoecke, Annelies ; Shatunov, Aleksey ; Simpson, Claire ; Lemmens, Robin ; Jaspers, Tom ; Fukami, Kiyoko ; Nakamura, Yoshikazu ; Brown, Robert H. ; Van Damme, Philip ; Liston, Adrian ; Robberecht, Wim ; Al-Chalabi, Ammar ; Van Den Bosch, Ludo. / Genetic ablation of phospholipase C delta 1 increases survival in SOD1G93A mice. In: Neurobiology of Disease. 2013 ; Vol. 60. pp. 11-17.
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