Abstract
Recent studies showed that the carotid sinus nerve (CSN) and the sympathetic nervous system (SNS) are overactivated in type 2 diabetes and that restoring the correct CSN neural activity can re-establish the proper metabolism. However, a robust characterization of the relationship between CSN and SNS neural activities and metabolism in type 2 diabetes is still missing. Here, we investigated the relationship between neural activity of CSN and SNS in control rats and in rats with diet-induced type 2 diabetes and the animal condition during metabolic challenges. We found that the diabetic condition can be discriminated on the basis of CSN and SNS neural activities due to a high-frequency shift in both spectra. This shift is suppressed in the SNS in case of CSN denervation, confirming the role of CSN in driving sympathetic overactivation in type 2 diabetes. Interestingly, the Inter-Burst-Intervals (IBIs) calculated from CSN bursts strongly correlate with perturbations in glycaemia levels. This finding, held for both control and diabetic rats, indicates the possibility of detecting metabolic information from neural recordings even in pathological conditions. Our results suggest that CSN activity could serve as a marker to monitor glycaemic alterations and, therefore, it could be used for closed-loop control of CSN neuromodulation. This paves the way to the development of novel and effective bioelectronic therapies for type 2 diabetes.
Highlights
T HE autonomic nervous system is essential for the maintenance of body homoeostasis
We aimed at addressing this issue by evaluating and characterizing the normal and pathological neural response of carotid sinus nerves (CSN) to metabolic stimuli. We described in both frequency and time domains the neural activities recorded in the CSN and in the cervical sympathetic nerve, during in vivoexperiments performed in control rats (CTL), and rats with type 2 diabetes induced by high-fat/high-sucrose diet (HFHSu)
As glucose levels returned to normoglycaemic values, approximately 90 minutes after the injection, insulin was administrated and the neural activity recorded for 20 minutes
Summary
T HE autonomic nervous system is essential for the maintenance of body homoeostasis. The antagonistic effects of its sympathetic and parasympathetic divisions regulate several basic functions, including heart rate, breathing rate, and metabolism. Overactivation of the sympathetic nervous system (SNS) is an autonomic dysfunction associated with hypertension (HT) as well to insulin resistance (IR) and glucose intolerance, typical features of type 2 diabetes mellitus [1]–[4]. The CB and the CSN have been shown to be both overactivated in IR and HT animal models induced by hypercaloric diets [9], [10] Supporting this hypothesis, CSN bilateral denervation was shown to prevent and reverse glucose intolerance, IR and HT as well as to avoid the increasing of sympathoadrenal activity in diet-induced prediabetic and type 2 diabetic rats [9], [11]. Surgical resection of the CSN is not a clinically usable solution since it produces side effects as the loss of the peripheral hypoxic response, decreased sensitivity to CO2 [12], [13], impaired response to exercise [14]–[16] and fluctuations in blood pressure [17]
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