Optogenetics studies of kisspeptin neurons

Ivanova, Deyana; O’Byrne, Kevin

doi:10.1016/j.peptides.2023.170961

Cited by 1 publication

(1 citation statement)

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“…Even though estradiol is considered the main regulator of gonadotropin release, GnRH and kisspeptin neurons express various glutamate and GABA receptors and respond to these neurotransmitters [ 100 , 101 ]. Different data converge to indicate that the LH surge is stimulated by glutamate [ 102 , 103 ] and inhibited by GABA [ 104 , 105 ], and that its occurrence is coincident with a decline of GABAergic transmission to both POA kisspeptin neurons and GnRH neurons [ 106 , 107 ].…”

Section: Resultsmentioning

confidence: 99%

Fibromyalgia pathogenesis explained by a neuroendocrine multistable model

Demori,

Losacco,

Giordano

et al. 2024

PLoS ONE

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Fibromyalgia (FM) is a central disorder characterized by chronic pain, fatigue, insomnia, depression, and other minor symptoms. Knowledge about pathogenesis is lacking, diagnosis difficult, clinical approach puzzling, and patient management disappointing. We conducted a theoretical study based on literature data and computational analysis, aimed at developing a comprehensive model of FM pathogenesis and addressing suitable therapeutic targets. We started from the evidence that FM must involve a dysregulation of central pain processing, is female prevalent, suggesting a role for the hypothalamus-pituitary-gonadal (HPG) axis, and is stress-related, suggesting a role for the HP-adrenocortical (HPA) axis. Central pathogenesis was supposed to involve a pain processing loop system including the thalamic ventroposterolateral nucleus (VPL), the primary somatosensory cortex (SSC), and the thalamic reticular nucleus (TRN). For decreasing GABAergic and/or increasing glutamatergic transmission, the loop system crosses a bifurcation point, switching from monostable to bistable, and converging on a high-firing-rate steady state supposed to be the pathogenic condition. Thereafter, we showed that GABAergic transmission is positively correlated with gonadal-hormone-derived neurosteroids, notably allopregnanolone, whereas glutamatergic transmission is positively correlated with stress-induced glucocorticoids, notably cortisol. Finally, we built a dynamic model describing a multistable, double-inhibitory loop between HPG and HPA axes. This system has a high-HPA/low-HPG steady state, allegedly reached in females under combined premenstrual/postpartum brain allopregnanolone withdrawal and stress condition, driving the thalamocortical loop to the high-firing-rate steady state, and explaining the connection between endocrine and neural mechanisms in FM pathogenesis. Our model accounts for FM female prevalence and stress correlation, suggesting the use of neurosteroid drugs as a possible solution to currently unsolved problems in the clinical treatment of the disease.

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