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Increased neuronal activity restores circadian function in Drosophila models of C9orf72-ALS/FTD - PubMed

3 days ago
  • #neuronal activity
  • #circadian rhythm
  • #ALS/FTD
  • Circadian rhythm disruptions are common in neurodegenerative diseases, including ALS and FTD.
  • The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD.
  • Drosophila models expressing pathogenic dipeptides (PR or GR) or GGGGCC repeats showed circadian deficits.
  • Circadian rhythmicity and period length were altered based on repeat number, dosage, expression pattern, and age.
  • Lower levels of the neuropeptide PDF, reduced projection complexity, and decreased neuronal activity were observed in PDF-expressing neurons.
  • Increased neuronal activity rescued mild circadian dysfunction across different models and ages.
  • The study highlights the role of reduced neuronal activity in C9orf72-ALS/FTD circadian deficits.