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Abstract
Sympathetic neurons of the rat superior cervical ganglion (SCG) can segregate their neurotransmitters and co-transmitters to separate varicosities of single axons. We have shown that transmitter segregation is a plastic phenomenon and that it is correlated with the strength of synaptic transmission. Here, we determined whether sympathetic dysfunction occurring in stress and hypertension was correlated with plastic changes of neurotransmitter segregation. We characterized the expression of the markers, L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine (ACh) transporter (VAChT) in the SCG of cold stressed and spontaneously hypertensive rats (SHR). Considering that the SCG comprises a heterogeneous neuronal population, we explored whether the expression and segregation of neurotransmitters would also have an intraganglionic heterogeneous distribution in ganglia of stressed and hypertensive rats. Furthermore, since hypertension in SHR is detected around 8–10 weeks, we evaluated expression and segregation of ACh and GABA in adult hypertensive (12-week old (wo)) and young pre-hypertensive (6-wo) SHR. We found an increase in segregation of ACh and GABA with no change in transmitter expression in ganglia of stressed animals. In contrast, in SHR, there was an increase in GABA expression, although segregation did not vary. Segregation showed a caudo-rostral gradient in controls but not in the ganglia of stressed animals. GABA expression showed a rostro-caudal gradient in adult SHR, which was not present in young 6-wo rats. In young SHR, ACh increased and, unexpectedly, segregation of ACh and GABA was higher than in adults. Data suggest that ACh and GABA segregation increases in acute sympathetic hyperactivity like stress, but does not vary in chronic hyperactivity such as in hypertension. Changes in segregation are age-dependent and might be involved in the mechanisms underlying stress and hypertension.
Highlights
The sympathetic nervous system (SNS) regulates many functions including blood pressure, cardiac contractility, intestinal motility and exocrine gland secretion, among others
Cold-Stress Enhanced Segregation of ACh-GABA in superior cervical ganglion (SCG) To assess the presence of stress and of sympathetic hyperactivity in cold exposed rats, we determined body weight and the expression of tyrosine hydroxylase (TH) in the adrenal medulla (AM)
Data presented here show that under both sympathetic overfunction conditions, cold stress and hypertension, the expression and segregation of neurotransmitters in the rat SCG varied differentially depending on the type of overfunction
Summary
The sympathetic nervous system (SNS) regulates many functions including blood pressure, cardiac contractility, intestinal motility and exocrine gland secretion, among others. We found a likely functional role of segregation in the rat superior cervical ganglia (SCG), we detected a correlation between the level of segregation of ACh and GABA, and the strength of synaptic transmission, where more segregation correlates with stronger synaptic transmission (Elinos et al, 2016) Considering this evidence regarding the plasticity of neurotransmitter segregation, and its likely functional roles, here we explored whether certain physio-pathologic conditions coursing with sympathetic dysfunction, like stress and hypertension, correlate with changes in the segregation of neurotransmitters in the rat SCG. We hypothesized that in stress and hypertension, SNS overactivity might change the distribution of ganglionic neurotransmitters in the SCG of the rat, to cope with sympathetic dysfunction To explore this hypothesis, we investigated the expression and segregation of ACh and GABA, by immunostaining of vesicular ACh transporter (VAChT) and L-glutamic acid decarboxylase of 67 kDa (GAD67), in animals subjected to cold stress, and in spontaneously hypertensive rats (SHR). We found greater segregation and higher GABA and ACh content in young SHR and control normotensive Wistar Kyoto (WKy) rats, compared to adults
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