Intramuscular Injection of BOTOX® Boosts Learning and Memory in Adult Mice in Association with Enriched Circulation of Platelets and Enhanced Density of Pyramidal Neurons in the Hippocampus

Neurochem Res. 2020 Dec;45(12):2856-2867. doi: 10.1007/s11064-020-03133-9. Epub 2020 Sep 24.

Abstract

BOTOX® is a therapeutic form of botulinum neurotoxin. It acts by blocking the release of acetylcholine (ACh) from the synaptic vesicles at the neuromuscular junctions, thereby inhibiting the muscle contraction. Notably, many neurological diseases have been characterized by movement disorders in association with abnormal levels of ACh. Thus, blockade of aberrant release of ACh appears to be a potential therapeutic strategy to mitigate many neurological deficits. BOTOX® has widely been used to manage a number of clinical complications like neuromuscular disorders, migraine and neuropathic pain. While the beneficial effects of BOTOX® against movement disorders have extensively been studied, its possible role in the outcome of cognitive function remains to be determined. Therefore, we investigated the effect of BOTOX® on learning and memory in experimental adult mice using behavioural paradigms such as open field task, Morris water maze and novel object recognition test in correlation with haematological parameters and histological assessments of the brain. Results revealed that a mild dose of BOTOX® treatment via an intramuscular route in adult animals improves learning and memory in association with increased number of circulating platelets and enhanced structural plasticity in the hippocampus. In the future, this minimally invasive treatment could be implemented to ameliorate different forms of dementia resulting from abnormal ageing and various neurocognitive disorders including Alzheimer's disease (AD).

Keywords: Acetylcholine; BOTOX®; Learning and memory; Morris water maze; Novel object recognition; Platelet count.

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / pharmacology*
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / drug effects
  • Injections, Intramuscular
  • Locomotion / drug effects
  • Male
  • Mice, Inbred BALB C
  • Morris Water Maze Test / drug effects
  • Open Field Test / drug effects
  • Platelet Count
  • Pyramidal Cells / drug effects*
  • Spatial Learning / drug effects*
  • Spatial Memory / drug effects*

Substances

  • Botulinum Toxins, Type A