Physical activity sustains memory retrieval in dopamine-depleted mice previously treated with L-Dopa

Behav Brain Res. 2019 Sep 2:369:111915. doi: 10.1016/j.bbr.2019.111915. Epub 2019 Apr 16.

Abstract

The neurodegenerative disorder Parkinson's disease affects motor abilities as well as cognition. The gold standard therapy is L-Dopa, which mainly restores motor skills. Therefore, we require additional interventions to sustain cognitive functions in Parkinson's disease. The lifestyle intervention "physical activity" improves adult hippocampal neurogenesis and memory but so far, its impact has not been investigated in rodent models for Parkinson's disease previously treated with the standard therapy. We hereby asked whether physical activity serves as a pro-neurogenic and -cognitive stimulus in dopamine-depleted mice previously treated with L-Dopa. Therefore, we injected dopamine-depleted mice with L-Dopa/Benserazide followed either by exercise or by a sedentary lifestyle. We analysed adult hippocampal neurogenesis histologically and assessed spatial memory in the Morris water maze. Furthermore, we investigated the hippocampal and striatal monoaminergic cross-talk. Physical activity prevented memory decline and was linked to a slower dopamine turnover but did not enhance neurogenesis in dopamine-depleted mice previously treated with L-Dopa. In conclusion, physical activity did not develop its full pro-neurogenic potential in mice previously treated with L-Dopa but sustained spatial cognition in Parkinson's disease.

Keywords: Hippocampal neurogenesis; L-Dopa; MPTP; Memory; Spatial cognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology*
  • Benserazide / adverse effects
  • Benserazide / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Drug Combinations
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Levodopa / adverse effects
  • Levodopa / pharmacology*
  • MPTP Poisoning / pathology
  • MPTP Poisoning / physiopathology
  • MPTP Poisoning / psychology
  • MPTP Poisoning / therapy*
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Random Allocation
  • Sedentary Behavior

Substances

  • Antiparkinson Agents
  • Drug Combinations
  • benserazide, levodopa drug combination
  • Green Fluorescent Proteins
  • Levodopa
  • Benserazide
  • Dopamine