Rivastigmine ameliorates botulinum-induced hippocampal damage and spatial memory impairment in male rats

Neurotoxicology. 2023 Sep:98:29-38. doi: 10.1016/j.neuro.2023.07.004. Epub 2023 Jul 26.

Abstract

Botulinum toxin (Botox) is widely used in beauty industry and its long-term consequences can be a matter of concern. The hippocampal cholinergic system plays a significant role in memory and learning that could be affected by Botulinum toxin. However, to date, the effect of Botox on memory system has been controversial. This survey aimed to examine the effects of Botox on spatial memory, and biochemical and histological parameters of the hippocampus in male rats by using Rivastigmine (R) as a cholinesterase inhibitor that is more selective for the central nervous system (CNS). Thirty-five male Wistar rats (200-250 g) were distributed into seven groups: Sham, Botox A (3, 6, and 15 IU intramascularly) and Botox A (3, 6, and 15 IU) plus Rivastigmine (1 mg/kg intraperitoneally). Spatial memory was assessed in the Morris Water Maze (MWM) 4 weeks later. Moreover, the hippocampal tissue was removed for histopathological and biochemical analyses. Botox significantly impaired memory performance in MWM by increasing escape latency and swim distance and decreasing the time spent in the target zone. Furthermore, in the Botox groups, the level of acetylcholine decreased, while the level of the acetylcholinesterase enzyme increased significantly in the hippocampus. Also, local lesions were observed in the form of degeneration and loss of pyramidal neurons, as well as a decrease in the volume and shrinkage of the cell body and an increase in microglia in the damaged area. Rivastigmine administration alleviated biochemical and histological parameters and partially ameliorated Botox-induced impairments. In summary, rivastigmine could be a suitable protective approach for side effects of Botox in the hippocampus.

Keywords: Acetylcholine; Acetylcholinesterase; Botulinum; Memory; Morris water maze; Rivastigmine.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Botulinum Toxins, Type A* / therapeutic use
  • Botulinum Toxins, Type A* / toxicity
  • Clostridium botulinum* / metabolism
  • Hippocampus
  • Male
  • Maze Learning
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Rats
  • Rats, Wistar
  • Rivastigmine / pharmacology
  • Rivastigmine / therapeutic use
  • Spatial Memory

Substances

  • Rivastigmine
  • Acetylcholinesterase
  • Botulinum Toxins, Type A