Sympathetic Hyperactivity and Age Affect Segregation and Expression of Neurotransmitters

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.

Ganglionic Long-Term Potentiation in Prehypertensive and Hypertensive Stages of Spontaneously Hypertensive Rats Depends on GABA Modulation

“…We confirmed the contribution of endogenous GABA in the expression of gLTP [30], and reported recently that GABA expression is greater in the SCG of SHR than in WKy [38]. According to the evidence that (i) heightened sympathetic nerve activity can be detected before the development of hypertension in SHR [22–25], (ii) GABA can block the occurrence of LTP in rat SCG of Wistar rats [33, 34], (iii) GABA presence can increase in SCG of SHR [38], and (iv) GABA has an antihypertensive central effect in SHR [39–41], we draw the following hypothesis: “early changes in neuroplasticity, particularly in the expression of gLTP, and its modulation by GABAergic inputs would be part of the mechanisms underlying neurogenic hypertension in SHR” .…”

“…We found that evoked gLTP in 12 wo SHR was masked by endogenous GABA, because the antagonism of GABA-A receptors by bicuculline unmasked the potentiation phenomenon. In support of this role of GABA, we have recently reported a greater presence of GABA-containing sympathetic varicosities in SCG of 12 wo SHR by comparison with WKy rats [38]. This effect of endogenous GABA might be related with reports of GABAergic antihypertensive effect in SHR.…”

“…To our knowledge, data reported here are the first evidence that changes in the synaptic plasticity of SCG occurred in SHR at early ages before hypertension develops. Although, there is currently controversy regarding the age of hypertension onset in SHR animals [24, 47], we and others found that 6 wo SHR are normotensive [25, 35, 38, 48].…”

“…gLTP was fully expressed in 6 wo SHR, despite the greater presence of GABA [38]. This can be explained by a larger segregation of ACh and GABA detected at 6 wo [38], which would reduce GABA inhibition [30]. By contrast with SHR, in WKy rats, endogenous GABA did not affect the expression of gLTP in 12 wo animals, but did mask the expression at 6 wo.…”

P2X receptors mediated abnormal interaction between satellite glial cells and neurons in visceral pathological changes

“…The axons of sympathetic postganglionic neurons organize the cardiac plexus and supply various parts of the heart, including the sinus node, the atrioventricular junction, the atrioventricular bundle, the atrial muscle, and the ventricular muscle. SCG and SG not only transmit sympathetic ganglion signals, but also play an integral role in the regulation of autonomic function (Tu et al, ; Liu et al, ; Zhang et al, ; Merino‐Jimenez et al, ). Thus, the cervical sympathetic ganglia can be viewed as a neural circuit that receives sensory visceral information and controls output to cardiovascular targets.…”