Single injection of very mild dose botulinum toxin in the vastus lateralis improves testicular spermatogenesis and sperm motility in ageing experimental mice.

BACKGROUND: Botulinum toxin (BoNT) is a widely used therapeutic agent that blocks the excessive release of acetylcholine at the neuromuscular junction. Previously, repeated intracremasteric injections and slight overdose of BoNT have been reported to induce adverse effects in the testicular parameter of experimental rodents. However, a mild dose of BoNT is highly beneficial against skin ageing, neuromuscular deficits, overactive urinary bladder problems, testicular pain and erectile dysfunctions. Considering the facts, the possible therapeutic benefits of BoNT on the testis might be achieved at a very minimal dosage and via a distal route of action. Therefore, we revisited the effect of BoNT, but with a trace amount injected into the vastus lateralis of the thigh muscle, and analyzed histological parameters of the testis, levels of key antioxidants and sperm parameters in ageing experimental mice. RESULTS: Experimental animals injected with 1 U/kg bodyweight of BoNT showed enhanced spermatogenesis in association with increased activities of key antioxidants in the testis, leading to enhanced amount of the total sperm count and progressive motility. CONCLUSIONS: This study signifies that a mild intramuscular dose of BoNT can be considered as a potent treatment strategy to manage and prevent male infertility.

BOTOX® counteracts the innate anxiety-related behaviours in correlation with increased activities of key antioxidant enzymes in the hippocampus of ageing experimental mice.

Cholinergic crisis and oxidative stress in the hippocampus of the brain have been known to induce anxiety disorders upon ageing. BOTOX® is a widely used therapeutic form of botulinum neurotoxin that acts by inhibiting the release of acetylcholine (ACh) from the nerve terminals at the neuromuscular junction. BOTOX® can migrate from the muscle to the brain through retrograde axonal transport and modulate neuroplasticity. While a mild dose of BOTOX® has been used to manage various neurological deficits and psychiatric complications including depression, the efficacy and experimental evidence for its anxiolytic effects and antioxidant properties remain limited. In this study, we have investigated the effect of BOTOX® on the innate anxiety-like behaviours in ageing mice upon exposure to different behavioural paradigms like open field test, elevated plus maze and light-dark box test, and estimated the enzymatic activities of key antioxidants in the hippocampus. Results revealed that animals injected with a mild intramuscular dosage of BOTOX® showed reduced level of innate anxiety-related symptoms and increased activities of hippocampal antioxidant enzymes compared to the control group. This study strongly supports that BOTOX® could be implemented to prevent or treat anxiety and hippocampal oxidative stress resulting from ageing, emotional and mood disorders.