Effects of bacterial melanin on motor recovery and regeneration after unilateral destruction of Substantia Nigra pars compacta in rats

We examined the potential neuroprotective action of bacterial melanin (BM) in rats after unilateral destruction of Substantia Nigra pars compacta (SNc) dopaminergic neurons. 24 rats were initially trained to an instrumental conditioned reflex (ICR) and then subjected to unilateral electrolytic destruction of SNc. Unilateral deficit in balancing hindlimb movements was observed in all rats after the destruction. On the next day after the destruction part of the animals (n = 12) was intramuscularly injected with BM solution at the concentration 6 mg/ml (0.17 g/kg). The other 12 operated rats served as a control group. On the second day after the operation the testing of instrumental conditioned reflex was resumed in both groups.     

Bilateral upregulation of α-synuclein expression in the mouse substantia nigra by intracranial rotenone treatment

The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson’s disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported. Clarification of this issue is important because an intracranial rotenone mouse model of Parkinson's disease has not been established. Towards this end, the present study examined the effects of intracranial rotenone treatment on TH and α-synuclein immunohistochemistry in addition to forelimb motor function. Mice were unilaterally infused with either vehicle or rotenone (2 μg/site) in both the medial forebrain bundle and the substantia nigra. The forelimb asymmetry (cylinder) test indicated a significant decrease in use of the contralateral forelimb in lesioned animals as compared to the sham group. Densitometric analysis revealed a significant depletion of TH immunofluorescence within the ipsilateral striatum and substantia nigra of lesioned animals. Moreover, a significant bilateral increase in α-synuclein immunofluorescence was found in the substantia nigra of lesioned mice, as compared to control animals. These findings indicate that this intracranial rotenone mouse model will be useful for studies of neurodegenerative disorders such as PD.     

Substantia nigra echogenicity correlated with clinical features of Parkinson's disease

BackgroundTranscranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.MethodsA total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.ResultsTwo hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.ConclusionsThis is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.     

Differentiating drug-induced parkinsonism from Parkinson's disease: An update on non-motor symptoms and investigations

Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management and prognosis. However, differentiating between these conditions can be challenging on a clinical ground, especially in the early stages. We therefore performed a review to ascertain whether assessment of non-motor symptoms, or use of ancillary investigations, namely dopamine transporter imaging, transcranial sonography of the substantia nigra, and scintigraphy for myocardial sympathetic innervation, can be recommended to distinguish between these conditions.Among non-motor symptoms, there is evidence that hyposmia can differentiate between patients with “pure” drug-induced parkinsonism and those with degenerative parkinsonism unmasked by an anti-dopaminergic drug. However, several issues, including smoking history and cognitive functions, can influence smell function assessment. Higher diagnostic accuracy has been demonstrated for dopamine transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac scintigraphy to predict dopaminergic pathway abnormalities and to differentiate between drug-induced parkinsonism and Parkinson's disease.Imaging of the dopaminergic pathway seems to be the only, reasonably available, technique to aid the differential diagnosis between drug-induced parkinsonism and Parkinson's disease.     

Isoprenylated phenolic compounds with tyrosinase inhibition from Morus nigra

A new isoprenylated sanggenon-type flavanone, nigrasin K (1), together with three known analogs (2–4) and five known Diels–Alder adducts (5–9), were isolated from the twigs of Morus nigra. Their structures were elucidated by spectroscopic methods. Sanggenon M (2), chalcomoracin (5), sorocein H (6), kuwanon J (7), sanggenon C (8), and sanggenon O (9) showed significant inhibitory effects on mushroom tyrosinase.     

Salidroside protects PC12 cells from MPP-induced apoptosis via activation of the PI3K/Akt pathway

Oxidative stress plays an important role in the pathogenesis of Parkinson’s disease (PD). Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., can exert potent antioxidant properties. In this study, we investigated the protective effects, and the possible mechanism of action, of SAL against 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell damage in rat adrenal pheochromocytoma PC12 cells. Pretreatment of PC12 cells with SAL significantly reduced the ability of MPP⁺ to induce apoptosis in a dose and time-dependent manner. SAL significantly and dose-dependently inhibited MPP⁺-induced chromatin condensation and MPP⁺-induced release of lactate dehydrogenase by PC12 cells. SAL enhanced Akt phosphorylation in PC12 cells, and the protective effects of SAL against MPP⁺-induced apoptosis were abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation. These findings suggest that SAL prevents MPP⁺-induced apoptosis in PC12 cells, at least in part through activation of the PI3K/Akt pathway.     

Neurometabolic profiles of the substantia nigra and striatum of MPTP‐intoxicated common marmosets: An in vivo proton MRS study at 9.4 T

Given the strong coupling between the substantia nigra (SN) and striatum (STR) in the early stage of Parkinson's disease (PD), yet only a few studies reported to date that have simultaneously investigated the neurochemistry of these two brain regions in vivo, we performed longitudinal metabolic profiling in the SN and STR of 1‐methyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐intoxicated common marmoset monkey models of PD (n = 10) by using proton MRS (¹H–MRS) at 9.4 T. T₂ relaxometry was also performed in the SN by using MRI. Data were classified into control, MPTP_2weeks, and MPTP_6‐10 weeks groups according to the treatment duration. In the SN, T₂ of the MPTP_6‐10 weeks group was lower than that of the control group (44.33 ± 1.75 versus 47.21 ± 2.47 ms, p < 0.05). The N‐acetylaspartate to total creatine ratio (NAA/tCr) and γ‐aminobutyric acid to tCr ratio (GABA/tCr) of the MPTP_6‐10 weeks group were lower than those of the control group (0.41 ± 0.04 versus 0.54 ± 0.08 (p < 0.01) and 0.19 ± 0.03 versus 0.30 ± 0.09 (p < 0.05), respectively). The glutathione to tCr ratio (GSH/tCr) was correlated with T₂ for the MPTP_6‐10 weeks group (r = 0.83, p = 0.04). In the STR, however, GABA/tCr of the MPTP_6‐10 weeks group was higher than that of the control group (0.25 ± 0.10 versus 0.16 ± 0.05, p < 0.05). These findings may be an in vivo depiction of the altered basal ganglion circuit in PD brain resulting from the degeneration of nigral dopaminergic neurons and disruption of nigrostriatal dopaminergic projections. Given the important role of non‐human primates in translational studies, our findings provide better understanding of the complicated evolution of PD.     

Linfocitos B reguladores en enfermedades humanas y modelos murinos de autoinmunidad

B lymphocytes belong to the adaptive immune system and they are responsible for humoral responses. In recent years, it has been demonstrated the existence of B cells with regulatory capacity (Breg) in humans and mouse models. The regulatory function of these B cells is explained by the production of IL-10 and the reduction of IFN-γ, TNF-α and IL-17 secretion by CD4 + T cells; in addition, Breg cells promote the differentiation of T lymphocytes into a regulatory phenotype and induce the remission of autoimmune manifestations in different murine models. In humans, alterations in number and function of Breg cells have been reported in systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Therefore, it has been suggested that Breg cells have an important role in the immunopathology of autoimmune diseases and may be a potential target for future treatments.     

The landmark contributions of Paul Blocq,Georges Marinesco,and Édouard Brissaud in Parkinson's disease

Two students of Jean-Martin Charcot, Paul Blocq and Georges Marinesco, presented a case of hemi-parkinsonism to the Société de Biologie on 27 May 1893. A tuberculoma was found at post-mortem in the cerebral peduncle contralateral to the side of the body affected by Parkinson's disease. A year later, in one of his lessons, Édouard Brissaud suggested that damage to the substantia nigra caused by the granuloma might have been responsible for the physical signs. This article provides brief biographical accounts of both Blocq and Marinesco and a detailed review of their seminal paper before going on to discuss how the substantia nigra was eventually established as the most consistent pathological substrate for Parkinson's disease and its role in the dopamine miracle which led to striatal dopamine replacement therapy in 1967.