Baicalein alleviates depression-like behavior in rotenone- induced Parkinson's disease model in mice through activating the BDNF/TrkB/CREB pathway

Biomed Pharmacother. 2021 Aug:140:111556. doi: 10.1016/j.biopha.2021.111556. Epub 2021 Jun 1.

Abstract

Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the world. In addition to motor symptoms, a variety of non-motor symptoms seriously affect the life quality of PD patients. Baicalein, a flavonoid extracted from the herb Scutellaria baicalensis Georgi, exhibits anti-PD activity through alleviation of its motor symptoms. However, its effects on non-motor symptoms were barely reported. This study aimed to investigate the therapeutic effects of baicalein on PD-related depression.

Methods: After a 2-week injection of rotenone, mice with PD-related depression behavior were selected, divided into three groups, and administrated saline, baicalein, or madopar orally for four weeks. Behavior, neuroinflammation, neurotransmitters, and synaptic plasticity were evaluated.

Results: Our results showed that 4-week baicalein treatment significantly alleviated the depression-like behavior in the rotenone-induced mice model. Repeated baicalein treatment reduced α-synuclein aggregation, inhibited neuroinflammation, and maintained neurotransmitters homeostasis. Moreover, we found that baicalein treatment could remarkably protect the synaptic plasticity and activate the BDNF/TrkB/CREB pathway in the PD-related depression mice model. As traditional dopamine replacement therapy unleashed few effects on depression-like symptom amelioration and synaptic function protection, baicalein might be a more appropriate choice for PD-related depression.

Conclusions: The current results suggested that baicalein could act as a treatment for PD-related depression.

Keywords: BDNF; Baicalein; Depression; Parkinson’s disease; Rotenone.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Depression / drug therapy*
  • Depression / metabolism
  • Disease Models, Animal
  • Flavanones / pharmacology*
  • Flavonoids / pharmacology
  • Homeostasis / drug effects
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects
  • Neuroprotective Agents / pharmacology
  • Neurotransmitter Agents / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Parkinson Disease / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Rotenone / adverse effects*
  • Signal Transduction / drug effects

Substances

  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Flavanones
  • Flavonoids
  • Membrane Glycoproteins
  • Neuroprotective Agents
  • Neurotransmitter Agents
  • Rotenone
  • baicalein
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases