Agonists of peroxisome proliferator-activated receptor-gamma attenuate the Abeta-mediated impairment of LTP in the hippocampus in vitro.

The data we present here suggest that agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma) can attenuate the effects of beta-amyloid peptide (Abeta). Alzheimer's disease is associated with elevated levels of Abeta, and enhanced expression of PPARgamma. In this study, we determined that application of Abeta([1-40]) could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPARgamma agonists; troglitazone, ciglitazone and 15-deoxy-delta(12,14) prostaglandin J2 (PGJ2) on synaptic transmission and plasticity in area CA1. Both ciglitazone and PGJ2 increased baseline synaptic transmission significantly, without altering paired-pulse facilitation. PGJ2 produced a significant reduction in LTP, whereas ciglitazone and troglitazone had no significant effect. In addition, prior application of each ligand attenuated the previously observed Abeta([1-40])-mediated impairment of LTP. The effect of troglitazone on the Abeta([1-40])-mediated impairment of LTP was not reversed by the PPARgamma antagonist, GW-9662. These findings demonstrate that PPARgamma agonists attenuate the effects of Abeta on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPARgamma agonists may regulate expression of hippocampal LTP in vitro.

Arterial chemoreceptors in the superior laryngeal nerve of the rat.

Paraganglia resembling the carotid body have been described in the superior laryngeal nerve (SLN) of the rat and the aim of the present study was to determine if this tissue is chemosensitive. We developed a novel isolated SLN preparation superfused with HEPES-buffered Tyrode solution at 35 degrees C in vitro. A glass suction microelectrode was used to record the electrical activity of single SLN units and a micropipette was used to pressure-eject small volumes of sodium cyanide (NaCN; 250-500 ng in 5 microl) near glomus tissue located at the main bifurcation of the SLN. The duration of the NaCN response and the number of spikes evoked after application of NaCN were compared in normoxia and hyperoxia (PO2 > 300 mmHg). Hyperoxia significantly reduced the duration and spike number of the NaCN response and a negative linear correlation existed between PO2 and response duration. In addition, hypoxia (PO2 < 60 mmHg) triggered SLN firing. Therefore, we can conclude that the paraganglia of the SLN are not only morphologically similar to the carotid body but are also excited by similar stimuli.

Discharge patterns of preganglionic neurones with axons in a cardiac vagal branch in the rat.

The fibre types that run in a vagal branch projecting to the rat heart are described in this study. In order to obtain spontaneous discharge in this vagal branch and optimal recording conditions, we compared the decerebrate state to urethane, urethane-chloralose and pentobarbital-chloralose anaesthesia with regard to level of chronotropic cardiac vagal tone. Administration of atropine (2 mg kg(-1), I.V.) significantly decreased baseline cardiac interval only in the decerebrate and urethane-anaesthetised rat (by 0.018 +/- 0.001 s and 0.019 +/- 0.002 s, respectively). As a result of these experiments, urethane was chosen as the anaesthetic for all subsequent studies. Using a heart rate signal-averaging method we demonstrated that rat cardiac vagal preganglionic neurones innervating the sinoatrial node should have an expiratory discharge pattern, as reported in other species. However, only 5 % of chronotropic vagal tone was found to be subject to respiratory sinus arrhythmia. A suction microelectrode method, combined with spike-triggered averaging, was employed to record activity from a total of 58 vagal afferents that had axons in this branch. Approximately 75 % of these latter sensory fibres displayed cardiac rhythm. In a separate study we also recorded 318 preganglionic neurones with axons in the right cardiac vagal branch of the rat. Respiratory-modulated preganglionic units were statistically less common than tonically firing units. Six preganglionic subtypes were categorised according to conduction velocity and respiratory discharge pattern. Myelinated B-fibre and unmyelinated C-fibre types were found to be equally prevalent and equally likely to be reflexly excited during the pulmonary chemoreflex and the peripheral arterial chemoreflexes. The electrophysiological analysis has shown how diverse the discharge patterns of the preganglionic neurones or interneurones are whose axons course in the right cardiac vagal branch of the rat. The results of these experiments demonstrate the usefulness of combining spike discrimination with multiple spike-triggered averaging to simultaneously record B and C centrifugal vagal efferents.

Vagal control of the cranial venae cavae of the rat heart.

The cranial venae cavae of the rat heart are composed of cardiac muscle. We tested whether the vagus nerve has an inotropic action on these blood vessels. Stimulation of right or left vagal fibres (n = 7 animals) produced a negative chronotropic and inotropic effect. Before stimulation the basal cardiac interval was 319 +/- 25 ms and the vena caval diastolic force was 1.82 +/- 0.29 mN and the systolic force was 3.28 +/- 0.39 mN. Ten second stimulation increased the cardiac interval to a maximum of 484 +/- 77 ms and reduced the systolic force significantly to 2.83 +/- 0.39 mN (two-tailed paired t test). The diastolic or baseline force was unaffected by vagal stimulation (1.85 +/- 0.29 mN). The vagal negative inotropic action took significantly longer to reach peak effect (9.5 +/- 1.0 s versus 3.2 +/- 0.9 s) and lasted longer than the chronotropic effect (20.4 +/- 2.1 s versus 10.25 +/- 1.2 s). The negative inotropic action was still observed in paced preparations and preparations with transient constant-rate tachyarrhythmias. Both the chronotropic and inotropic effects were abolished by atropine (10(-6) M) and mimicked by acetylcholine chloride (10 nM). In order to minimize an atrial contribution to the force production a more reduced preparation was used and ganglion clusters at the cavo-atrial junction were stimulated electrically (n = 4 animals). Similar negative inotropic and chronotropic effects sensitive to hexamethonium were seen. After hexamethonium administration, positive inotopic and chronotropic effects were uncovered and these were abolished by atenolol (0.1 mg %). Methylene Blue staining of the preparation at the end of the experiment showed the presence of ganglion cells at the sites of stimulation. Ganglion clusters were never seen on the venae cavae per se. The results of this investigation show that the vagus has a powerful action on the venae cavae resembling that on the atria and mediated by acetylcholine.