Neurobiology of Aging 31 (2010) 805–812 In vivo expression of ganglionic long-term potentiation in superior cervical ganglia from hypertensive aged rats K.H. Alzoubi a , A.M. Aleisa b , K.A. Alkadhi c,∗ a Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan b King Saud University, College of Pharmacy, Riyadh, Saudi Arabia c Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Central Campus, SR-2 Room 521E, Houston, TX 77204-5515, USA Received 20 January 2008; received in revised form 15 April 2008; accepted 11 June 2008 Available online 22 July 2008 Abstract Sustained increase in central sympathetic outflow to ganglia may provide the repeated high frequency presynaptic activity required for induction of long-term potentiation in sympathetic ganglia (gLTP), which is known to be involved in the manifestation of a neurogenic form of hypertension, namely stress-hypertension. Aging is often viewed as a progressive decline in physiological competence with a corresponding impaired ability to adapt to stressful stimuli. Old animals have exaggerated sympathetic activity as well as increased morbidity and mortality during prolonged exposure to stressful stimuli. Using the superior cervical ganglion (SCG) as a model for sympathetic ganglia, electrophysiological and biochemical evidence show that mildly hypertensive aged rats (22-month old) have expressed gLTP in vivo. This is suggested by a number of lines of evidence. Firstly, a shift in input/output (I/O) curve of ganglia from aged rats to the left side of I/O curve of ganglia from 6-month old (adult) rats indicating expression of gLTP. Secondly, failure of in vitro high frequency stimulation to induce gLTP in ganglia isolated from aged rats, which indicates occlusion due to saturation, which, in turn, suggests in vivo expression of gLTP in these ganglia. Thirdly, in vitro inhibition of basal ganglionic transmission by blockers of gLTP (5-HT 3 antagonists) is observed in ganglia isolated from aged rats, but not in those from adult rats. Finally, immunoblot analysis revealed that protein levels of signaling molecules such as calcium-calmodulin kinase II (CaMKII; phosphorylated and total), which normally increase during expression of LTP, are elevated in ganglia isolated from aged rats compared to those from adult ones. Protein levels of calcineurin, which dephosphorylates P-CaMKII, were reduced in ganglia isolated from aged rats, probably as a support mechanism to allow prolonged phosphorylation of CaMKII. Our findings suggest in vivo expression of gLTP in sympathetic ganglia of aged animals, which may contribute to the moderate hypertension often seen in aged subjects. © 2008 Elsevier Inc. All rights reserved. Keywords: CaMKII; Calcineurin; Ondansetron; I/O curve; 5-HT 3 antagonist 1. Introduction Ganglionic long-term potentiation (gLTP) of the superior cervical ganglion (SCG) is a serotonin-dependent (Alkadhi et al., 1996), protracted enhancement of the nicotinic pathway that has been demonstrated both in vivo (Alonso-deFlorida et al., 1991; Bachoo et al., 1992; Bachoo and Polosa, 1992) and in vitro (Brown and McAfee, 1982; Briggs et al., 1985; Minota et al., 1991; Alkadhi et al., 1996). Expression of ∗ Corresponding author. Tel.: +1 713 743 1212; fax: +1 713 743 1229. E-mail address: kalkadhi@uh.edu (K.A. Alkadhi). gLTP is independent of activation of cholinergic, adrener- gic (Briggs et al., 1985) and adenosine (Hogan et al., 1998) receptors and does not involve changes in the acetylcholine (ACh) content of the ganglion (Briggs et al., 1985) or the sensitivity of nicotinic ACh receptors (Briggs and McAfee, 1988; Briggs et al., 1988). Induction and maintenance of gLTP require activation of 5-HT 3 receptors (Alkadhi et al., 1996) by serotonin that is probably released by high fre- quency stimulation (HFS) from “intraganglionic structures including the” serotonin-containing small intensely flores- cent (SIF) cells within the SCG (Hadjiconstantinou et al., 1982). 0197-4580/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2008.06.007