THE NEUROEXPLORISTS
Modelling Interplay between Stress and Reproduction
Kate Nechyporenko, 2nd year PhD, University of Exeter
BACKGROUND:
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Throughout a woman's life, the reproductive function plays an important role due to its impact on physical and emotional health. Stress is a factor that interferes with the reproductive system, disturbing hormone production, as a result, may cause irregular periods and affect fertility. The processing of stress signals is associated with the amygdaloid brain region. Specifically, the posterodorsal medial amygdala (MePD) has been implicated in the modulation of luteinizing hormone (LH) pulsatility. Recent experimental evidence indicates that neuronal activity within the MePD is regulated by neuropeptide kisspeptin providing excitatory input to populations of glutamate and γ-aminobutyric acid (GABA) which in turn project to nuclei in the hypothalamus. However, the mechanisms underpinning possible dynamic behaviours of the MePD neuronal network are not fully understood.
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METHODOLOGY:
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I am currently developing and analysing a mean-field model that captures the interplay of cooperative and competitive dynamics between GABA and glutamate neuronal populations in the MePD under the upstream input from kisspeptin. Using bifurcation analysis, I study how changes in the kisspeptin-mediated input influence the dynamics in the network.
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RESULTS:
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I validate the model by simulating how MePD output modulates KNDy (kisspeptin, Neurokinin B, Dynorphin) neuronal population in the arcuate nucleus, a small region in the hypothalamus of the brain, that is considered as a proxy for the LH pulsatility. I have shown that stimulation of MePD kisspeptin leads to a decrease in the KNDy pulse frequency (Fig(a)), but the combination of stimulation with the suppression of GABAergic signalling causes the opposite effect, increasing the frequency of pulses (Fig(d)). As a result. the proposed mechanisms do well to explain the effects of MePD kisspeptin optogenetic stimulation and its combination with GABA receptor antagonism.
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Fig: Simulation of the effects of the MePD outputs on the KNDy model. Gl, Gi, Ge, Gp represent the populations of glutamatergic neurons, GABA interneurons, GABA efferents, and kisspeptin neurons in the MePD, respectively. (a) baseline MePD kisspeptin, (b) stimulated MePD kisspeptin, (c) baseline MePD kisspeptin and suppression of GABA signalling, (d) stimulated MePD kisspeptin & suppression of GABA signalling.
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FUTURE WORK:
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My ultimate aim is to use experimental and clinical knowledge and findings to inform a mathematical model that takes into account the effects of stress factors, such as strenuous exercise and mental disorders, on the cycle. Ideally, I would like to consider both, acute and chronic stress conditions, and develop a theoretical framework that could be applied across the life span, from menarche to menopause as well as in the case of fertility treatments such as in vitro fertilisation (IVF) treatments.
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FUNDED BY:
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CONTACT:
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@KVNechyporenko
