Basal ganglia in Parkinson’s disease

Obeso, J.A., Rodriguez-Oroz, M.C., Rodriquez, M., Lanciego, J.L., Artieda, J., Gonzalo, N. (2000) Pathophysiology of the basal ganglia in Parkinson s disease. Trends Neurosci 23, S8-S19. 

Wichmann T, DeLong MR (2003) Functional neuroanatomy of the basal ganglia in Parkinson s disease. Adv Neurol 91 9-18... 

Basal ganglia are a group of subcortical nuclei which are essential for the coordination of movements (so-called extrapyramidal system). They include the caudate nucleus, putamen, globus pallidus, and lenti-form nucleus. Damage of the basal ganglia results in involuntary movements, as are observed in Parkinson s disease and Huntington s chorea. 

Figure 15.2(b) A schematic presentation of possible basal ganglia circuitry in Parkinson s disease. In PD there is little or no inhibitory nigrostriatal input to the striatum so the Ind Path is active and GPext is inhibited. This will then have less depressant effect on the SThN which will be free to drive the GPint (and SNr) and so reduce cortico-thalamic traffic and produce akinesia. See text for detail. Pathway activity — low — normal — high... 

Functional circuitry between the cortex, basal ganglia, and thalamus. The major neurotransmitters are indicated. In Parkinson s disease, there is degeneration of the pars compacta of the substantia nigra, leading to overactivity in the indirect pathway (red) and increased glutamatergic activity by the subthalamic nucleus. 

FIGURE 11 —4. When dopamine 2 receptors are blocked by dopamine 2 antagonists in the postsynaptic projections of the nigrostriatal pathway, it produces disorders of movement, which can appear very much like those in Parkinson s disease. That is why these movements are sometimes called drug-induced parkinsonism. Since the nigrostriatal pathway projects to the basal ganglia, a part of the so-called extrapyramidal nervous system, side effects associated with blockade of dopamine 2 receptors there are sometimes also called extrapyramidal symptoms (EPS). 

Dopamine autoreceptors play a role in Parkinson s disease, schizophrenia and drug addiction. Dopamine heteroreceptors affecting the release of acetylcholine and of amino acid neurotransmitters in the basal ganglia are also relevant for Parkinson s disease. Peripheral dopamine heteroreceptors on postganglionic sympathetic terminals influence heart rate and vascular resistance through modulation of noradrenaline release. 

Anichtchik OV, Rinne JO, Kalimo H, Panula P (2000) An altered histaminergic innervation of the substantia nigra in Parkinson s disease. Exp Neurol 163 20-30 Anichtchik OV, Peitsaro N, Rinne JO, Kalimo H, Panula P (2001) Distribution and modulation of histamine H3 receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson s disease. Neurobiol Dis 8 707-16... 

Neurodegenerative changes in basal ganglia as in Parkinson s disease, Huntington s chorea, Wilson s disease... 

Figure 13.2. Section through the brain showing the location of the areas of the basal ganglia that are dysfunctional in Parkinson s disease.

Because of the key role which dopamine plays in basal ganglia function, and the evidence that its deficiency results in Parkinson s disease, there are three main approaches to the effective treatment of the symptoms of the disease ... 

Marsden, C., Obeso, J. (1994). The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson s disease. Brain, 117, 877-897. 

The D2 receptor distribution in the basal ganglia structures has been extensively studied in relation to the role of these receptors in the control of movements and their involvement in Parkinson s disease, as it has happened for all the other features of the organization and regulation of the dopaminergic innervation of the striatum. 

Ingham CA, Stephens B, Arbuthnott GW (2002) Structural plasticity in Parkinson s disease. In Faull RLM, Nicholson LFB (Eds), The Basal Ganglia Structure and Function VII, pp. 333-340. Kluwer Academic Publishing, Boston. 

Annett LE, Rogers DC, Dunnett SB (1990b) Unilateral 6-OHDA lesions in marmosets a primate model for neural transplantation in Parkinson s disease. In Franks AJ, Ironside J, Mindham RHS, Smith RJ, Spokes EGS, Winlow W (Eds), Function and Dysfunction in the Basal Ganglia, pp. 181-197. Pergamon, Oxford. 

Parent A, Lavoie B (1993b) Dopaminergic innervation of the basal ganglia in normal and parkinsonian monkeys. In Schneider JS, Gupta M (Eds), Current Concepts in Parkinson s Disease Research, pp. 403 414. Hogrefe and Huber, Toronto. 

Sian, J., Dexter, D. T., Lees, A. J., Daniel, S., Agid, Y., etal., Alterations in glutathione levels in Parkinson s disease and other neurodegenerative disorders affecting the basal ganglia. Ann. Neurol. 36, 348-355 (1994). 

Q8 Acetylcholine is normally in balance with dopamine in the basal ganglia, but in Parkinson s disease dopamine levels are reduced and the effects of acetylcholine become more pronounced. To restore the balance, antimuscarinic agents are used to antagonize the excitatory actions of acetylcholine. They seem to be effective for tremor and reduce the secretion of saliva, digestive juices and sweat. 

Blandini F, Nappi G, TassoreUi C, Martignoni E (2000) Functional changes in the basal ganglia circuitry in Parkinson s disease. Prog Neurobiol 62 63-88... 

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