Microdialysis in Parkinsonian Patient Basal Ganglia: Acute Apomorphine-Induced Clinical and Electrophysiological Effects Not Paralleled by Changes in the Release of Neuroactive Amino Acids

doi:10.1006/exnr.2000.7568

Experimental Neurology

Volume 167, Issue 2, February 2001, Pages 356-365

https://doi.org/10.1006/exnr.2000.7568 Get rights and content

Abstract

During stereotaxic neurosurgery for deep brain stimulation in Parkinson's disease (PD), we performed a microdialysis study of the extracellular amino acid (aspartate, glutamate, glycine, and GABA) concentrations. Their levels were measured in the GPe/GPi of five and in the STN of four different PD patients, after prolonged therapy washout. The results show stable values of basal release of the examined amino acids within 1 h. The basal levels of GABA in “OFF” state were significantly higher in the GPi than in the GPe. Acute apomorphine administration, while inducing clinical amelioration and electrophysiological changes in the examined nuclei, did not change amino acid concentrations. This result could be related to a limited microdialysis ability to detect subtle changes in amino acid spontaneous release. Alternatively, it could suggest that dopaminergic receptors located in the output nuclei, possibly present also in humans, might mediate the acute apomorphine clinical effects, not involving amino acid changes along the direct and/or indirect pathway.

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Serotonergic control of the glutamatergic neurons of the subthalamic nucleus
2021, Progress in Brain Research
The subthalamic nucleus (STN) houses a dense cluster of glutamatergic neurons that play a central role in the functional dynamics of the basal ganglia, a group of subcortical structures involved in the control of motor behaviors. Numerous anatomical, electrophysiological, neurochemical and behavioral studies have reported that serotonergic neurons from the midbrain raphe nuclei modulate the activity of STN neurons. Here, we describe this serotonergic innervation and the nature of the regulation exerted by serotonin (5-hydroxytryptamine, 5-HT) on STN neuron activity. This regulation can occur either directly within the STN or at distal sites, including other structures of the basal ganglia or cortex. The effect of 5-HT on STN neuronal activity involves several 5-HT receptor subtypes, including 5-HT_1A, 5-HT_1B, 5-HT_2C and 5-HT₄ receptors, which have garnered the highest attention on this topic. The multiple regulatory effects exerted by 5-HT are thought to be modified under pathological conditions, altering the activity of the STN, or due to the benefits and side effects of treatments used for Parkinson's disease, notably the dopamine precursor l-DOPA and high-frequency STN stimulation. Originally understood as a motor center, the STN is also associated with decision making and participates in mood regulation and cognitive performance, two domains of personality that are also regulated by 5-HT. The literature concerning the link between 5-HT and STN is already important, and the functional overlap is evident, but this link is still not entirely understood. The understanding of this link between 5-HT and STN should be increased due to the possible importance of this regulation in the control of fronto-STN loops and inherent motor and non-motor behaviors.
Subthalamic nucleus deep brain stimulation on motor-symptoms of Parkinson's disease: Focus on neurochemistry
2017, Progress in Neurobiology
Deep brain stimulation (DBS) has become a standard therapy for Parkinson’s disease (PD) and it is also currently under investigation for other neurological and psychiatric disorders. Although many scientific, clinical and ethical issues are still unresolved, DBS delivered into the subthalamic nucleus (STN) has improved the quality of life of several thousands of patients.
The mechanisms underlying STN-DBS have been debated extensively in several reviews; less investigated are the biochemical consequences, which are still under scrutiny. Crucial and only partially understood, for instance, are the complex interplays occurring between STN-DBS and levodopa (LD)-centred therapy in the post-surgery follow-up.
The main goal of this review is to address the question of whether an improved motor control, based on STN-DBS therapy, is also achieved through the additional modulation of other neurotransmitters, such as noradrenaline (NA) and serotonin (5-HT). A critical issue is to understand not only acute DBS-mediated effects, but also chronic changes, such as those involving cyclic nucleotides, capable of modulating circuit plasticity.
The present article will discuss the neurochemical changes promoted by STN-DBS and will document the main results obtained in microdialysis studies. Furthermore, we will also examine the preliminary achievements of voltammetry applied to humans, and discuss new hypothetical investigational routes, taking into account novel players such as glia, or subcortical regions such as the pedunculopontine (PPN) area.
Our further understanding of specific changes in brain chemistry promoted by STN-DBS would further disseminate its utilisation, at any stage of disease, avoiding an irreversible lesioning approach.
Letter to the Editor
2013, Journal of Neuroscience Methods
Multi-target strategy for Parkinsonian patients: The role of deep brain stimulation in the centromedian-parafascicularis complex
2009, Brain Research Bulletin
The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the basal ganglia and is recently regaining its position has a putative neurosurgical target for Parkinsonian syndromes. The multi-target approach we have encouraged since the late nineties has allowed the combined implantation of a standard target (the subthalamic nucleus—STN or the internal pallidus—GPi) plus an innovative one (CM/Pf) in well-identified Parkinson’s disease (PD) patients; hence, it is possible to study, in the same PD patients, the specific target-mediated effects on different clinical signs.
Here, we focus on the potential usefulness of implanting the CM/Pf complex when required in the management of contra-lateral tremor (resistant to standard deep brain stimulation—DBS – in STN – , n = 2) and disabling involuntary movements, partially responsive to GPi–DBS (n = 6). When considering global UPDRS scores, CM/Pf–DBS ameliorate extra-pyramidal symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very powerfully on tremor and contributes to the long-term management of l-Dopa-induced involuntary movements.
The lack of cognitive deficits and psychic impairment associated with the improvement of their quality of life, in our small cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and attractive area for surgical treatment of advanced PD, possibly affecting not only motor but also associative functions.
Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the nucleus accumbens of cocaine-treated rats
2008, Neuroscience
Citation Excerpt :
A few in vivo studies demonstrated significant changes in the ultrastructural localization of GPCRs in response to modulation of extracellular activating neurotransmitter (Dumartin et al., 1998, 2000; Bernard et al., 2003; Toda et al., 2003; Stanwood and Levitt, 2007). However, in MPTP-treated mice, an experimental condition characterized by a significant increase in glutamatergic transmission in the subthalamic nucleus and globus pallidus (Mally et al., 1997; Fedele et al., 2001; Wichmann and DeLong, 2003), very little, if any, changes were induced in the subsynaptic and subcellular distribution of group I mGluRs in these nuclei (Kuwajima et al., 2007). Together, these findings highlight the unique intrinsic properties of group I mGluRs compared with other GPCRs in their response to changes in ambient activating transmitter levels.
There is significant pharmacological and behavioral evidence that group I metabotropic glutamate receptors (mGluR1a and mGluR5) in the nucleus accumbens play an important role in the neurochemical and pathophysiological mechanisms that underlie addiction to psychostimulants. To further address this issue, we undertook a detailed ultrastructural analysis to characterize changes in the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the core and shell of nucleus accumbens following acute or chronic cocaine administration in rats. After a single cocaine injection (30 mg/kg) and 45 min withdrawal, there was a significant decrease in the proportion of plasma membrane–bound mGluR1a in accumbens shell dendrites. Similarly, the proportion of plasma membrane–bound mGluR1a was decreased in large dendrites of accumbens core neurons following chronic cocaine exposure (i.e. 1-week treatment followed by 3-week withdrawal). However, neither acute nor chronic cocaine treatments induced significant change in the localization of mGluR5 in accumbens core and shell, which is in contrast with the significant reduction of plasma membrane–bound mGluR1a and mGluR5 induced by local intra-accumbens administration of the group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG). In conclusion, these findings demonstrate that cocaine-induced glutamate imbalance has modest effects on the trafficking of group I mGluRs in the nucleus accumbens. These results provide valuable information on the neuroadaptive mechanisms of accumbens group I mGluRs in response to cocaine administration.
Bilateral implantation in Globus Pallidus internus and in subthalamic nucleus in Parkinson's disease
2005, Neuromodulation
Citation Excerpt :
After implantation, we used X-ray photography of the skull under stereotactic conditions in both AP and LL projections to check if there were any differences between programmed coordinates and those actually surgically performed (3P Maranello computerized re-calculation system, CLS SRL). In the postoperative period we performed our clinical assessments and macro recordings directly from the DBS electrodes (11–21) using different patterns of contacts and modes of stimulation in order to verify the efficacy of DBS, either with a single target stimulated (mono or bilaterally), or with both targets stimulated. After testing we checked the position of the electrodes utilizing MRI and/or CT.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and of the pars interna of Globus Pallidus (GPi) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications in Parkinson’s disease (PD) (DBS for PD study group, 2001). It is still not clear what the best anatomic structures to stimulate are or what the physiologic effects of DBS are. Most of the studies regarding DBS for parkinsonian symptoms have been conducted in patients with STN implantation, and these studies reported significant improvement in motor function with a relatively low rate of complication. The large experience of ablative surgery associated with the DBS experience of some groups worldwide indicate that GPi is a possible and very promising target for the management of parkinsonian symptoms. Surgical procedures have become safer and it is now possible, in selected cases, to target both structures in the same patient by means of the stereotactic system, “3P Maranello” (CLS-SRL, Italy). Using this system we were able to evaluate the clinical effects of simultaneous stimulation of both STN and GPi as well as evaluate the effects of isolated stimulation of each target. As it is known that there is a high intersubject variability of DBS, it seems relevant to test all different combinations of DBS in the same patient.
We assessed the effects of DBS in 13 cases of PD, immediately after (30 min) stimulation and during chronic stimulation (weeks or months). Patients fell into two groups. The first (n = 7) responded to both GPi and STN stimulation equally. The second group (n = 6) was preferentially stimulated with only one target (STN = 5, GPi = 1).
There was a good reduction in levodopa treatment following surgery. Most patients remained were chronically treated with bilateral stimulation of both targets.
We conclude that DBS of STN and GPi was effective, with most patients treated chronically with both targets stimulated.

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Regular ArticleMicrodialysis in Parkinsonian Patient Basal Ganglia: Acute Apomorphine-Induced Clinical and Electrophysiological Effects Not Paralleled by Changes in the Release of Neuroactive Amino Acids

Abstract

Trends Neurosci.

Lancet

Neuroscience

Brain Res.

Neuroscience

Neuroscience

Neurosci. Res.

Neurosci. Lett.

Trends Neurosci.

Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Brain Res.

Neurosurg. Clin. N. Am.

Lancet

Life Sci.

Neuropharmacology

Brain Res.

Neuroscience

Exp. Neurol.

Epilepsy Res.

Pallidal stimulation for Parkinson's disease—Two targets?

Neurology

The striatum and the globus pallidus send convergent synaptic inputs onto single cells in the entopeduncular nucleus of the rat: A double anterograde labelling study combined with postembedding immunocytochemistry for GABA

J. Comp. Neurol.

Quantitative autoradiographic localization of the D1 and D2 subtype of dopamine receptors in the rat brain

J. Neurosci.

Validity of some neuropsychological tests in the assessment of mental deterioration

Acta Psychiatr. Scand.

Unified Parkinson's disease rating scale

Nicotine administration stimulates the in vivo N-methyl-d-aspartate receptor/nitric oxide/cyclic GMP pathway in rat hippocampus through glutamate release

Br. J. Pharmacol.

Differential neuronal activity in segments of globus pallidus in Parkinson's disease patients

NeuroReport

Regular Article
Microdialysis in Parkinsonian Patient Basal Ganglia: Acute Apomorphine-Induced Clinical and Electrophysiological Effects Not Paralleled by Changes in the Release of Neuroactive Amino Acids

Nicotine administration stimulates the in vivo N-methyl- $d$ -aspartate receptor/nitric oxide/cyclic GMP pathway in rat hippocampus through glutamate release