Parkinson disease results from disorder of nigrostriatal pathway
Case 136
【Progress】She continued to conduct rehabilitation for two months according to the initial plan. Her left hemiparesis improved from paresis degree of 1/5 to 4/5.
【Discussion】
There are four dopamine pathways in the brain; meso-cortical, meso-limbic, nigrostriatal and tubero-hypophyseal (1). Mesocortical pathway from the ventral tegmentum to the prefrontal cortex is involved in cognitive control, motivation and emotional response. Meso-limbic pathway from the ventral tegmentum to the nucleus accumbence is involved in rewarding stimuli. Tubero-hypophyseal pathway from the arcuate nucleus or infudibular nucleus in the tuberal region of the hypothalamus to the median eminence in the hypothalamus, involved in the secretion of prolactin. Nigrostriatal pathway from the substantia nigra pars compacta to the caudate nucleus and putamen is involved in motor coordination.
The motor processing regarding the basal ganglion has two pathways: an encouraging pathway and an inhibitory pathway. Basal ganglions compose of putamen, caudate nucleus (external and internal), subthalamic nucleus and substantia nigra (pars compacta, pars reticulata) (2-4). Dopamine works in an encouraging pathway as a neurotransmitter and γ aminobutyric acid (GABA) works in an inhibitory pathway as a neurotransmitter. Because dopamine neurons become depleted in Parkinson disease, an encouraging pathway is getting lost, inducing the inhibitory pathway is usually activated. That is why the clinical features of Parkinson disease bring about tremors, rigidity and postural imbalance.
Parkinson disease results from dysfunction of nigrostriatal pathway. In short, the hallmarks of Parkinson disease are macroscopically the loss of the dark pigmented dopamine neurons in the substance nigra and microscopically the emergence and increase of Lewy bodies in neurons of the substance nigra (2 - 4). Lewy body is mainly composed of α synuclein. In Parkinson disease, mitochondrial functions which produce energy by adenosine triphosphate are impaired in the process of oxidative phosphorylation. Mitochondrial dysfunction and oxidative damage induce aggregation of synuclein. Autophagy is one of the innate mechanisms of dissolving proteins inside a cell itself (5). Hyperfunction of autophagy is known to be activate in case of starvation. When autophagy function for dissolving α synuclein is impaired, Lewy body might be formed. The accumulation of Lewy body induces production of active oxygen, leading to cell death. Then, Parkinson disease results from mitochondrial dysfunction and autophagy hypofunction, inducing accumulation of α synuclein, leading to damage and loss of dopamine neuron in the substance nigra.
As radiological imaging, dopamine transporter (DAT) scan shows hot accumulation at putamen and caudate nucleus in a healthy person indicating the normal release of dopamine, while in patients with Parkinson’s disease, it shows a significant reduction in the release of dopamine. In 3T-MRI with T2*, absent swallow tail sign and drop-out (disappearance) of normal signal intensity of substantia nigra and red nuclei (6). Regrettably, our hospital cannot supply RI scan and 3T-MRI.
【Summary】
We present an eighty six-year-old female with acute infarction of left frontal lobe and Parkinson disease. It is borne in mind that four dopamine pathways exist in the brain; meso-cortical, meso-limbic, nigrostriatal and tubero-hypophyseal and they function cognitive control, motivation and emotional response, rewarding, secretion of prolactin and motor coordination, respectively. There are two pathways as motor processing of basal ganglion: an encouraging pathway and an inhibitory pathway. Dopamine works in an encouraging pathway as a neurotransmitter and γ aminobutyric acid (GABA) works in an inhibitory pathway as a neurotransmitter. Because dopamine neurons become depleted in Parkinson disease, an encouraging pathway is getting lost, inducing the inhibitory pathway is usually activated. The hallmarks of Parkinson disease are macroscopically the loss of the dark pigmented dopamine neurons in the substance nigra and microscopically the emergence and increase of Lewy bodies in neurons of the substance nigra. Lewy body is mainly composed of α synuclein. Autophagy is one of the innate mechanisms of dissolving proteins inside a cell itself. Parkinson disease results from mitochondrial dysfunction and autophagy hypofunction, leading loss of dopamine neuron in the substance nigra. Dopamine transporter (DAT) scan shows in patients with Parkinson’s disease, a significant reduction in the release of dopamine. In MRI with T2*, absent swallow tail sign and drop-out (disappearance) of normal signal intensity of substantia nigra and red nuclei.
【References】
1.Tritsch, NX; Ding, JB; Sabatini, BL (Oct 2012). "Dopaminergic neurons inhibit striatal output through non-canonical release of GABA". Nature. 490 (7419): 262–6. doi:10.1038/nature11466. PMC 3944587. PMID 23034651.
2.Deumens, Ronald (21 June 2002). "Modeling Parkinson's Disease in Rats: An Evaluation of 6-OHDA Lesions of the Nigrostriatal Pathway". Experimental Neurology. 175 (2): 303–17.
3.Olanow CW, et al. Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci. 1999;22:123-44.
4.Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain. 1991;114 ( Pt 5): 2283-301.
5.Sato S, et al. Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice. Scientific Reports. 2018 ; 8, Article number: 2813
6.Schwarz ST, et al. The 'swallow tail' appearance of the healthy nigrosome - a new accurate test of Parkinson's disease: a case-control and retrospective cross-sectional MRI study at 3T. PLoS ONE. 2014;9 (4): e93814.
2019.1.23