engleski

Neurotransmitter Based Countermeasures for Post Spaceflight Vestibular Deconditioning

PURPOSE: The purpose of this paper is to propose a countermeasure strategy based on modulation of vestibular neurotransmitters. Although several postflight vestibular deconditioning countermeasure strategies are being developed, no operational strategy presently exists. With the prospect of extended human exploration missions, there is a need develop postflight countermeasures that would allow human crews to operate unhindered and without delay in gravity environments after prolonged exposure to microgravity. Short-term exposure to microgravity causes vestibular readaptation followed by deconditioning upon return to nominal gravity conditions. Changes in the background force environment cause vestibular deconditioning manifested in vestibulo-ocular/-spinal reflex decompensation and ataxias. The neurobehavioral effects of postflight vestibular deconditioning cause significant risk to the crew and successful performance of mission tasks. Advances in selective pharmacological modulation of neurotransmitter activity introduce a possibility of using major vestibular neurotransmitters (Acetylcholine, Glutamate, GABA, Glycine) as modulators of vestibular sensory output. By controlling the sensory output to the integration areas in the cortex, partial influence may be exerted on the emanating vestibulo-ocular and vestibulo-spinal responses. METHODOLOGY: A survey of technical capabilities and existing vestibular deconditioning strategies has been conducted. Pharmacological properties of four major vestibular neurotransmitters have been investigated. Research into pharmacological capabilities of selective synaptic modulation (release/reuptake) of neurotransmitters in the CNS has been conducted. Based on the performed research a neurotransmitter-based postflight vestibular deconditioning strategy has been proposed for the major vestibular neurotransmitters. RESULTS: Pharmacological properties of four major vestibular neurotransmitters – Acetylcholine, Glutamate, GABA, Glycine were investigated. Anticholinergic medication (scopolamine) is effectively being used to treat SMS and related symptoms. Selective modulation of Ach synaptic activity could be achieved by increased local availability of acetylcholinesterase. Modulation of Glutamate (excitatory) activity may be achieved through selective blocking of mGlur receptors which would reduce the synaptic time of glutamate and reduce its excitatory effect on sensory signal transmission. The time of synaptic activity for GABA and Glycine (inhibitory) could be extended by introducing glycine reuptake inhibitors and GABA A/B receptor agonists. This would allow for prolonged glycine and GABA activity at respective sites of action. CONCLUSION: Preparation of extended human exploration missions requires development of operational countermeasures for postflight vestibular deconditioning. Neurotransmitter-based countermeasures employing selective synaptic release/reuptake modulation of major vestibular neurotransmitters (ACh, GABA, Glutamate, Glycine) offer prospect for development of applicable postflight countermeasures. ACKNOWLEDGEMENTS: This study was supported by the Research project #0196003 of the Ministry of Science, Education and Sports of the Republic of Croatia.

Neurotransmitter; Countermeasures; Vestibular; Deconditioning

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