Fig. 5
From: A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice
Histamine reuptake critically shapes Stress Index (Si). A This equation describes Si. The first term is a Heaviside function that acts as a switch filtering the state of the system as either control or stress based on the histamine concentration. A value of zero is ascribed to this term when the histamine concentration equals the basal histamine level. Furthermore, the second term describes the impact histamine levels above the basal histamine value has on Si which is a linear rise. The last term describes the contribution of serotonin towards Si which either alleviates or exacerbates stress-induced behavior in an exponential manner. B Schematic illustration of the metric Si. Si is a positive scalar function that grades stress based on histamine and serotonin steady-state levels. A Si value of zero corresponds to controls and an increasing value of Si is associated with higher stress. In this model, Si associated with the maximum IHA = 2*104 nMs−1 corresponds to a high level of stress. Furthermore, the normal condition with IHA = 1250 nMs−1 corresponds to basal or lower histamine levels and the stressed condition is associated with heightened histamine levels and significant reduction in serotonin levels. C, D Variation in Si under a two-fold increase and decrease in the parameter of interest while keeping rest of the parameters fixed. Dark red (magenta) bars refer to a two-fold increase (decrease) in the parameter. The blue bar refers to Si for the basal condition i.e. when all the parameters are set to their basal value. C The Si values for normal conditions are shown. A Si of zero exists for basal values of the parameters, shown here in blue bar. It may also be noticed that spanning a parameter range doesn’t cause a significant change in Si. D Si values for the stressed condition are also shown. The basal values of the various parameters are τHA = 0.8 s−1, τ5HT = 0.8 s−1, α = 69.7961 s−1, β = 0.0013 s−1, I5HT = 56.3250 nMs−1 and IHA = 1250 nMs−1 for control and IHA = 2*104 nMs−1 for stress are obtained by fitting the model to the experimental data. Variation in histamine reuptake rate τHA causes the most significant change in Si