Effects of Neuropsychopharmalogical Treatment on the Synaptic Plasticity of Murine Primary Hippocampal Neurons

Abstract

Neurodegeneration is not only a major issue in ongoing ages, but also astronauts show neuropsychological and -physiological symptoms under changing gravity conditions. The loss of synaptic plasticity associated with that is highly undesirable and consequently a countermeasure is required with implications not only for long-term spaceflights, but also for the treatment of neurodegenerative diseases. A promising drug candidate for aforementioned issues is ketamine, which is well-established for anaesthesia and found recent application as an antidepressant. However, low oral bioavailability as well as several side effects renders ketamine unsuitable for long-term treatment, motivating the development of novel derivatives. Therefore, the present study aims to elucidate the impact of novel ketamine derivatives, provided by the group of Prof. Dr. Sherif El Sheikh at the University of Applied Sciences Cologne, on murine primary hippocampal neurons. The cells were cultured for 21 days in vitro and with the aforementioned compounds in several concentrations for varying times. Subsequently, neurons were immunostained and the preand post-synaptic number of boutons was analyzed. Indeed, the number increased at some derivatives compared to the commonly used ketamine. Same results are shown by the BDNF (Brain-derived neutrophic factor) level in the supernatant of the cells.