The long-term effects of Δ9-tetrahydrocannabinol on microtubule dynamicity in rats

Arch Biochem Biophys. 2020 Oct 30:693:108574. doi: 10.1016/j.abb.2020.108574. Epub 2020 Sep 6.

Abstract

Studies reported that Δ9-tetrahydrocannabinol (Δ9-THC) is an essential drug as an anti-cancer, neuroprotective, anti-inflammatory, and immune-modulatory agent. However, the mechanism by which Δ9-THC causes these events remains to be elucidated. We attempted to investigate the in vivo studies of Δ9-THC on brain microtubule dynamicity, and acetylcholinesterase (AChE) activity. The microtubule polymerization, secondary and tertiary structures of α/β-tubulins, as well as the AChE activity, were evaluated in the experimental groups. The significantly lowest optical density and initial rate of polymerization was observed in THC 3 mg/kg, THC 9 mg/kg, and THC 18 mg/kg treated groups. The content of secondary and tertiary structures of α/β-tubulins was significantly affected in treated groups. The AChE activity was significantly lower in treated groups in a dose-dependent manner. These data highlight the microtubule dynamicity as a molecular target for Δ9-THC, which affects memory dysfunction. However, Δ9-THC can be inhibited the AChE activity and provide an improved therapeutics for neurodegenerative diseases.

Keywords: AChE activity; ATP (PubChem CID: 5957); GTP (PubChem CID: 6830); Memory function; Microtubule dynamicity; THC (CAS # 34675-49-5); Δ(9)-THC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Animals
  • Cholinesterase Inhibitors / pharmacology
  • Circular Dichroism
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Microtubules / drug effects*
  • Polymerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Tubulin / chemistry
  • Tubulin / drug effects
  • Tubulin / isolation & purification

Substances

  • Cholinesterase Inhibitors
  • Tubulin
  • Dronabinol
  • Acetylcholinesterase