Altered light-dark phase-dependent behavioral responses and suprachiasmatic nucleus pathology in an α-synuclein rat model of Parkinson’s disease

Jun 19, 2026NPJ Parkinson's disease

Changes in daily activity patterns and internal clock problems in a rat model of Parkinson's disease

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Abstract

Behavioral testing revealed robust phase-dependent modulation of exploratory activity and other behaviors in wild-type rats, which was absent in α-synuclein-overexpressing rats.

  • α-synuclein-overexpressing rats showed no phase-dependent modulation in exploratory activity, locomotion, sucrose preference, and olfaction-guided feeding.
  • Histological analyses indicated reduced cell density and increased α-synuclein accumulation in the suprachiasmatic nucleus of α-synuclein rats.
  • Altered cellular composition was observed in the suprachiasmatic nucleus, including changes in neuronal, orexinergic, and microglial markers.
  • A positive correlation was found between α-synuclein load and the counts of Orexin A fibers and Iba1 cells, suggesting a link to neuroinflammation.
  • These findings indicate that α-synuclein rats exhibit early suprachiasmatic nucleus pathology and a lack of phase-dependent behavioral changes.

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Full Text

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