Positron Emission Tomography of Striatal Serotonin Transporters in Parkinson Disease

Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05). Conclusion LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.

show abstract

“…The mean ISI coefficient of variation (0.52±0. 18) was significantly lower than the value in normal rats (P < 0.05; Fig. 4).…”

Section: Resultsmentioning

confidence: 69%

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In basal ganglia, for example, 5-HT exerts a phasic inhibitory control over GABA synthesis and release [36]. Parkinson patients display a reduced level of striatal serotonin binding sites [30] and transporters [92]; accordingly, the selective 5-HT uptake inhibitor citalopram, associated to L-DOPA treatment, was reported to alleviate both bradykinesia and depressive symptoms [34,156]. Therefore, a more detailed investigation for the precise role of 5-HT receptors controlling GABA-mediated transmission in basal ganglia might offer new perspectives in the therapy of Parkinson disease.…”

Section: Role In Motor Controlmentioning

confidence: 99%

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Ciranna

2006

268

170

View full text Add to dashboard Cite

Abstract:The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a "classical" neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus on the modulatory action of 5-HT on the effects of glutamate and -amino-butyric acid (GABA), which are the principal neurotransmitters mediating respectively excitatory and inhibitory signals in the CNS. Examples of interaction at preand/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.

show abstract

“…Reduced brain levels of all of the key markers for the 5-HT neurotransmitter system provide compelling evidence for a striatal serotonergic abnormality in PD. This evidence has been confirmed by antemortem studies and imaging investigations that showed reduced cerebrospinal fluid levels of 5-HIAA and decreased activity of 5-HTT not only in the caudate nucleus and the putamen but also in the thalamus and medial frontal areas, indicating a pathophysiological involvement of 5-HT in PD (Haapaniemi et al, 2001;Kerenyi et al, 2003;Kim et al, 2003). It is, however, very likely that the degree of serotonergic degeneration depends on the stage of the disease .…”

Section: -Ht In Pd and Other Motor Disordersmentioning

confidence: 78%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

133

View full text Add to dashboard Cite

Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

show abstract

Positron Emission Tomography of Striatal Serotonin Transporters in Parkinson Disease

Abstract: These results suggest that the density of serotonin transporters, like that of dopamine transporters, is reduced in the striatum of patients with PD and that these changes are related to disease stage.

Cited by 134 publications

References 42 publications

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Contact Info

Product

Resources

About