Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H. Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Ting

doi:10.1016/j.jns.2014.12.014

Cited by 22 publications

(24 citation statements)

References 38 publications

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“…These data indicated that DA neurons in basal ganglia especially the GPe and SNr area played a vital role in the regulation of motor function. The GPe area was critical for the regulation of motor function, and a previous study also showed that DA neuron-depletion in the GPe area induced significant movement impairment [38]. In our study, TRPC1 depletion was shown to cause movement disorder in the mice, which could be a consequence of the loss of the DA neurons in basal ganglia caused by TRPC1 depletion.…”

Section: Discussionsupporting

confidence: 67%

Movement deficits and neuronal loss in basal ganglia in TRPC1 deficient mice

Guo

et al. 2016

Oncotarget

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Transient receptor potential cation (TRPC) channel proteins are abundantly expressed in brain. However, the functions of these TRPC proteins such as TRPC1 are largely unclear. In this study, we reported that TRPC1 deficiency caused movement disorder as measured by swimming test, modified open field test and sunflower seeds eating test. Immunofluorescent staining showed significant loss of both NeuN-positive cells and tyrosine hydroxylase (TH) -positive cells in the caudate putamen (CPu), the external globus pallidus (GPe), and the substantia nigra pars reticulata (SNr) in 5-month-old TRPC1 knockout mice (TRPC1−/−) compared to the wild type (WT) mice. TUNEL staining further revealed that TUNEL-positive cells were significantly increased in the CPu, GPe, and SNr of TRPC1−/− mice. Taken together, these data suggests that TRPC1 is involved in the control of motor function by inhibiting the apoptosis of neuronal cells of basal ganglia.

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Section: Discussionsupporting

confidence: 67%

Movement deficits and neuronal loss in basal ganglia in TRPC1 deficient mice

Guo

et al. 2016

Oncotarget

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“…Notably, as pointed out also by Kwak et al . 12 , the increases in connectivity are in line with the observed increased synchronicity in corticostriatal networks in dopamine depleted conditions 36 , 37 , including PD 38 . Nevertheless, despite functional connectivity increases in OFF conditions have been consistently reported 12 , 13 , 31 , 32 , whether they represent purely pathological signatures or compensatory mechanisms is still a matter of debate 39 .…”

Section: Discussionsupporting

confidence: 74%

Unraveling connectivity changes due to dopaminergic therapy in chronically treated Parkinson’s disease patients

Ballarini

Růžička

Bezdíček

et al. 2018

Sci Rep

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The effects of dopaminergic therapy for Parkinson’s disease (PD) on the brain functional architecture are still unclear. We investigated this topic in 31 PD patients (disease duration: 11.2 ± (SD) 3.6 years) who underwent clinical and MRI assessments under chronic dopaminergic treatment (duration: 8.3 ± (SD) 4.4 years) and after its withdrawal. Thirty healthy controls were also included. Functional and morphological changes were studied, respectively, with eigenvector centrality mapping and seed-based connectivity, and voxel-based morphometry. Patients off medication, compared to controls, showed increased connectivity in cortical sensorimotor areas extending to the cerebello-thalamo-cortical pathway and parietal and frontal brain structures. Dopaminergic therapy normalized this increased connectivity. Notably, patients showed decreased interconnectedness in the medicated compared to the unmedicated condition, encompassing putamen, precuneus, supplementary motor and sensorimotor areas bilaterally. Similarly, lower connectivity was found comparing medicated patients to controls, overlapping with the within-group comparison in the putamen. Seed-based analyses revealed that dopaminergic therapy reduced connectivity in motor and default mode networks. Lower connectivity in the putamen correlated with longer disease duration, medication dose, and motor symptom improvement. Notably, atrophy and connectivity changes were topographically dissociated. After chronic treatment, dopaminergic therapy decreases connectivity of key motor and default mode network structures that are abnormally elevated in PD off condition.

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“…Although the GP itself is not a dopamine-rich structure, its function within the basal ganglia network is, however, dependent on dopaminergic inputs. 42, 43, 44 Unlike other regions such as the putamen, which accumulate iron slowly but steadily throughout the lifespan, iron concentration in the GP increases rapidly during the first two decades of life (when iron is essential for growth and myelination), and then begins to plateau around the age of 30 years. 21 GP iron concentration in our CUD group not only exceeded that of age-matched healthy volunteers (mean age 40 years), but also correlated strongly with the duration of cocaine use (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Disrupted iron regulation in the brain and periphery in cocaine addiction

et al. 2017

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Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction.

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Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats

Cited by 22 publications

References 38 publications

Movement deficits and neuronal loss in basal ganglia in TRPC1 deficient mice

Movement deficits and neuronal loss in basal ganglia in TRPC1 deficient mice

Unraveling connectivity changes due to dopaminergic therapy in chronically treated Parkinson’s disease patients

Disrupted iron regulation in the brain and periphery in cocaine addiction

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