Substantia Nigra Area Research Articles

Capsaicin Protects Against Oxidative Insults and Alleviates Behavioral Deficits in Rats with 6-OHDA-Induced Parkinson's Disease via Activation of TRPV1.

Increasing evidence suggests that capsaicin may play a role in modulating neuronal function and controlling motor behavior. However, the underlying mechanism is still unclear and the activation of transient receptor potential vanilloid 1 (TRPV1) might be involved in. This study investigated the potential neuroprotective role of capsaicin in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Capsaicin was treated intraperitoneally for the 6-OHDA induced PD rats and the locomotor activity and abnormal involuntary movements were found alleviated. Besides, brain oxidative stress (lipid peroxidation, superoxide dismutase and catalase) was also assessed, and oxidative insults were investigated relieved. Both the expression of tyrosine hydroxylase and TRPV1 were increased in the striatal and substantia nigra areas of 6-OHDA induced rats after the treatment of capsaicin by the semi-quantitative analysis of Western Blot. And the immunostaining of substantia nigra further suggested that capsaicin might protect against dopaminergic neuronal loss. Our results showed that TRPV1 might be a novel therapeutic target for PD.

Structural changes of substantia nigra in patients with unilateral Parkinson′s disease

Magnetic resonance imaging (MRI) findings were studied in 19 patients with non-dementia Parkinson′s disease (PD) Hoehn-Yahr Stage 1 and 1.5 and 38 healthy subjects. The width and area of pars compacta of substantia nigra (SNc), substantia nigra (SN) and midbrain were measured. The width and area ratios of SNc to SN were calculated. Compared with controls, the widths of right SNc was narrower, bilateral ratios of SNc to SN width were decreased in PD group. As to the area of substantia nigra, there was no significant difference between PD and controls. The width of left SN and the ratio of right SNc to SN width was negatively correlation with age of patients. The ratio of left SNc to SN width, the area of bilateral SNc and left SN, as well as the ratio of right SNc to SN area had negative correlation with the disease duration; however, there was no correlation with gender, Hoehn-Yahr Stage, the Unified Parkinson disease rating scale score, mini mental state scale, education years, levodopa equivalent daily dose, Hamilton Depression Scale or Hamilton Anxiety Scale in PD group. The results indicate that there are bilateral structural changes of SN in unilateral PD patients, which may be more significant with increasing disease duration. The measurement of SNc width and SN area can be used as an objective indicator for diagnosis and disease progression monitoring of PD. Key words: Parkinson disease; Magnetic resonance imaging; Pars compacta of substantia nigra

Utilidad del ultrasonido transcraneal en Neurología y Neuropsiquiatría

The basal mesolimbic system is among the dopaminergic systems that undergo changes during human evolution and that, under certain conditions, connectivity and abnormal neurotransmission trigger pathological changes during adolescence and adulthood. Transcranial ultrasound in adults is performed through the temporal squama with equipment that has a focal sectorial transducer from 1.8 to 2.8MHz. The key points of the ultrasound evaluation are mesencephalon, substantia nigra area, raphe, striatum and thalamus, third ventricle, and orbitofrontal sectors. Despite its limited anatomical access, it is one of the neuroimaging methods that quantifies the echogenicity (0-3) and the sectional area of the substantia nigra (normal up to 0.2 cm2), which correlates with the worsening of Parkinsonian motor symptoms. It also evaluates and measures the raphe (normal 1mm) which correlates with humour or apathy.Thickness changes of the mesencephalic tegmentum (interpeduncularangle, smaller or greater than 60°), thalamus and striatum increased echogenicity, and the third ventricle dilation (greater than 5mm), are other possible findings. These are used to corroborate the diagnosis, classification, treatment and monitoring of different pathologies, like Parkinson's disease, supranuclear progressive palsy, dystonias, cortico-basal degeneration, schizophrenia, depression, bipolar disorder, and autism.

Study on transcranial sonography in patients with idiopathic rapid eye movement sleep behavior disorder

Objective To investigate the changes of transcranial sonography (TCS) in patients with rapid eye movement sleep behavior disorder (RBD). Methods Fifteen patients fulfilled the diagnostic criteria of RBD according to International Classification of Sleep Disorders (ICSD, 2nd edition). Under the monitor of polysomnography (PSG), the sleep architectures of all RBD cases were evaluated by Polysmith software and visual analysis. Furthermore, all RBD patients and 15 normal controls underwent TCS. Cases with substantia nigra echo intensity over Ⅲ grade and substantia nigra area over 0.20 cm 2 were supposed to be hyperechogenicity. Additionally, the width of the third ventricle was measured and whether there was hyperechogenicity in basal ganglia was evaluated. The cognitive functions were evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Results RBD patients presented typical clinical manifestations and electrophysiologic changes. No significant difference ( P = 0.080, 0.109) was found in the comparison of hyperechogenicity rate on substantia nigra (6/15) and basal ganglia (7/15) in RBD patients and normal controls (1/15, 2/15). No significant difference in the comparison of MoCA was found in RBD patients with or without substantia nigra hyperechogenicity ( P = 0.075). The RBD patients with hyperechogenicity on basal ganglia had higher MMSE scores than those without hyperechogenicity on basal ganglia, and the difference was significant ( P = 0.021). Conclusions RBD which is suggested as the prodromal period of synucleinopathy may present hyperechogenicity in substantia nigra and basal ganglia on TCS. TCS could detect subclinical changes of brain and evaluate the risk of synucleinopathy. DOI: 10.3969/j.issn.1672-6731.2016.04.010

Light pigmentation phenotype is correlated with increased substantia nigra echogenicity.

This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinson's disease. In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects. Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning. Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease.

Lipoic acid protects dopaminergic neurons in LPS-induced Parkinson's disease model.

Parkinson's disease (PD) is a chronic neurodegenerative disease of the central nervous system (CNS), characterized by a loss of dopaminergic neurons, which is thought to be caused by both genetic and environmental factors. Recent findings suggest that neuroinflammation may be a pathogenic factor in the onset and progression of sporadic PD. Here we explore the potential therapeutic effect of lipoic acid (LA) on a lipolysaccharide (LPS)-induced inflammatory PD model. Our results for the first time showed that LA administration improved motor dysfunction, protected dopaminergic neurons loss, and decreased α-synuclein accumulation in the substantia nigra (SN) area of brain. Further, LA inhibited the activation of nuclear factor-κB (NF-κB) and expression of pro-inflammatory molecules in M1 microglia. Taken together, these results suggest that LA may exert a profound neuroprotective effect and is thus a promising anti-neuroinflammatory and anti-oxidative agent for halting the progression of PD. Interventions aimed at either blocking microglia-derived inflammatory mediators or modulating the polarization of microglia may be potentially useful therapies that are worth further investigation.

Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

Echogenicity of basal ganglia structures in different Huntington's disease phenotypes.

In Huntington's disease (HD), a neurodegenerative-inherited disease, chorea as the typical kind of movement disorder is described. Beside chorea, however, all other kinds of movement disturbances, such as bradykinesia, dystonia, tremor or myoclonus can occur. Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington's disease phenotypes. 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington's Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of substantia nigra (SN) correlated positively with CAG repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN hyperechogenicity was significantly more often detectable in the juvenile form (100 vs. 29.3 %, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. HD patients with the juvenile variant exhibit marked hyperechogenicity of substantia nigra. No significant differences in basal ganglia echogenicities between predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes were detected.

Expression of dopamine transporter in the different cerebral regions of methamphetamine-dependent rats.

To observe the expression of the dopamine transporter (DAT) in six cerebral regions of a methamphetamine (MA)-dependent rat, which were frontal cortex, nucleus accumbens septi, striatum, hippocampus, substantia nigra and ventral tegmental area. The rats were administrated intraperitoneally with 10 mg/kg/day of MA for 10 days consecutively; the behaviour changes were measured via the conditioned place preference (CPP), and the scores of stereotyped behaviour (SB) were used to confirm animal addiction. Then, the animals were further injected with MA respectively for 1, 2, 4 and 8 weeks to establish different periods of MA-dependent models. The expressions of DAT and DAT messenger RNA in six cerebral regions were detected. The results of CPP and SB scores were significant different when comparing all four experimental groups with the control group (p < 0.05). Comparing between different experimental groups, the expression of DAT mainly decreased and had dynamic changes in the same regions (p < 0.05). Comparing the different regions with each other in the same experimental group, the expression of DAT also had significant difference in several regions p < 0.05). The expression of DAT mainly decreased and had different in the six cerebral regions at the same MA-dependent time period as well as at different time periods in the same cerebral region. It was speculated that DAT might play a crucial role in the mechanism of MA dependence.

Investigation of Complaint for Specific Swallowing Drugs in Parkinson Disease Patients

Introduction: Parkinson disease is a universal and neurodegenerative pathology that affects the basal ganglia, resulting in progressive death of cells producing the neurotransmitter dopamine present in the substantia nigra area of the brain, responsible for motor control part of the human body. The drug intervention in Parkinson is the main form of treatment for the disease and control signs and symptoms.

E27 Different Huntington's Disease Phenotypes And Echogenicity Of Basal Ganglia Structures

Background Beside Chorea all other kinds of movement disorders, such as bradykinesia, dystonia, tremor or myoclonus can occur in Huntington’s disease. Aim: Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington’s disease phenotypes. Method 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington’s Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. Results There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of Substantia nigra (SN) correlated positively with CAG-repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN-hyperechogenicity was significantly more often detectable in the juvenile form (100% vs. 29.3%, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. Discussion HD patients with the juvenile variant exhibit marked hyperechogenicity of Substantia nigra. Thus, a distinct different underlying pathophysiology of the disease in juvenile compared to adult HD is discussed.

Transcranial sonography of the substantia nigra: digital image analysis.

Increased echogenicity of the substantia nigra is a typical transcranial sonography finding in Parkinson disease. Experimental software for digital analysis of the echogenic substantia nigra area has been developed. The aim of this study was to compare the evaluation of substantia nigra echogenicity by using digital analysis with a manual measurement in patients with Parkinson disease and healthy volunteers. One hundred thirteen healthy volunteers were enrolled in the derivation cohort, and 50 healthy volunteers and 30 patients with Parkinson disease, in the validation cohort. The substantia nigra was imaged from the right and left temporal bone window by using transcranial sonography. All subjects were examined twice by using different sonographic machines by an experienced sonographer. DICOM images of the substantia nigra were encoded; then, digital analysis and manual measurement of the substantia nigra were performed. The 90th percentile of the derivation cohort values was used as a cut-point for the evaluation of the hyperechogenic substantia nigra in the validation cohort. The Spearman coefficient was used for assessment of the correlation between both measurements. The Cohen κ coefficient was used for the assessment of the correlation between both measurements and Parkinson disease diagnosis. The Spearman coefficient between measurements by using different machines was 0.686 for digital analysis and 0.721 for manual measurement (P < .0001). Hyperechogenic substantia nigra was detected in the same 26 (86.7%) patients with Parkinson disease by using both measurements. Cohen κ coefficients for digital analysis and manual measurement were 0.787 and 0.762, respectively (P < .0001). The present study showed comparable results when measuring the substantia nigra features conventionally and by using the developed software.

Morphofunctional interaction of CART peptide and dopaminergic brain neurons

In Wistar rats, after 6 h of sleep deprivation and subsequent 2 h postdeprivation sleep, we found significant changes in optical density of CART-peptide in neurons of hypothalamic nucleus accumbens and nucleus arcuatus as well as in processes coming into substantia nigra from nucleus accumbens. The obtained data revealed unidirectional changes of optical density of tyrosine hydroxylase: a decrease after sleep deprivation (p < 0.05) and, on the contrary, an increase on the background of postdeprivation sleep (p < 0.05). Confocal laser microscopy showed morphological connections of CART and dopaminergic neurons and possible colocalization of these both substances in the same neuron at the postdeprivation sleep. In experiments in vitro, after 1 h of incubation of survived brain slices from the substantia nigra area in the medium with CART-peptide there was revealed a rise of optical density of tyrosine hydroxylase in the substantia nigra compact part by 55 % (p < 0.05). The obtained data indicate an activating effect of CART-peptide on brain dopaminergic neurons and its as a modulator of their functional activity.

Sonographic abnormality of the substantia nigra in melanoma patients

Evidence derived from large epidemiological studies suggests an association between Parkinson's disease (PD) and malignant melanoma. Transcranial sonography of the midbrain reveals an extended echogenic substantia nigra (SN) area in a high proportion of patients with PD. This characteristic, in the context of PD, may signal degeneration of dopaminergic nigrostriatal projection neurons. Demonstration of an increased prevalence of abnormal echogenic SN in melanoma patients could add weight to the hypothesis of an underlying common pathogenic pathway of both diseases. This was a cross-sectional observational study. Transcranial sonography of the SN region was performed on 31 patients suffering from malignant melanoma and 29 healthy participants. In addition, patients and controls were screened for motor and non-motor symptoms of PD. The echogenic SN area was abnormally extended in 42% of melanoma patients versus 7% of control subjects (χ(2) = 9.811, P = .002). Mean echogenic SN area (SN[R, L]) was significantly larger in melanoma patients than in controls (patients, 0.21 ± 0.07 cm(2); controls, 0.15 ± 0.04 cm(2) [mean ± SD]; unpaired t test, P < .001). These findings provide additional evidence in favor of a common pathogenic pathway of PD and malignant melanoma and raise the possibility that their association is closer than previously assumed.

Experimental study on dynamic regulation of acetylcholine in striatum of rat parkinson disease model and behavior observation

In order to explore the role of acetylcholine in the pathogenesis of Parkinson's disease (PD), the changes in the concentration of acetylcholine (Ach) in the striatum, the apoptosis of substantia nigra cells, the ultrastructure and the changes of Nissl cells in rats during the morbidity of PD, and the corresponding behaviors in rats with PD were observed. Rat PD model was established by using the modified Thomas method. Eighty-one rats were randomly divided into normal control, sham operation and PD groups and their behavior features were observed at post-operative day (POD) 7, 14 and 21 as three subgroups (n=9 each). The concentration of Ach in the striatum was determined by using high-performance liquid chromatography. The apoptosis of substantia nigra cells was assayed by using TUNEL method. The ultrastructural changes in the substantia nigra were observed under the electron microscopy, and the survival of neurons in the substantia nigra area was examined by using Nissl staining. In PD group at POD 7 to 21, the damage in the substantia nigra area was gradually aggravated, the concentration of Ach, apoptosis rate and turns of rotation were gradually increased, and the number of Nissl cells was gradually reduced over the time as compared with the normal control and sham operation groups (all P<0.05). It was concluded that there exist dynamic changes in Ach concentration, ethology and apoptosis of the substantia nigra cells during the morbidity of PD, suggesting the contribution of apoptosis to the morbidity of PD, and critical role of Ach in the pathogenesis of PD.

Different Interactions of Prolyl Oligopeptidase and Neurotensin in Dopaminergic Function of the Rat Nigrostriatal and Mesolimbic Pathways

Prolyl oligopeptidase (PREP) is an intracellular enzyme digesting small proline-containing peptides. Since PREP resides the same brain areas as neurotensin in the nigrostriatal and mesolimbic dopaminergic pathways, we were interested to study if there is an intracellular interaction between them. A colocalization of PREP with neurotensin and neurotensin receptor 1 (NTS1) in the rat striatum, nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) was studied with immunofluorescence. From the same brain areas, the levels of dopamine and its metabolites were measured 1h after the injection of saline, NTS1 ligands (JMV-449; 5μg) or antagonist (SR142948; 5μg) to the rat striatum or NAcc. We also studied whether an intraperitoneal injection of a PREP inhibitor (KYP-2047; 5mg/kg) affects the levels of dopamine and its metabolites alone or modifies the effects of the NTS1 ligands. PREP was highly colocalized with neurotensin and NTS1 in the VTA, and with NTS1 in the SN. Colocalization was moderate or low in other brain areas. When injected to the striatum, JMV-449 had a tendency to increase dopamine (p=0.052) and metabolite levels in the striatum and SN, whereas SR142948 did not. After the injection to the NAcc, JMV-449 but not SR142948, increased dopamine levels in the VTA and dopamine metabolite levels in the NAcc and VTA. KYP-2047 decreased the dopamine levels in the striatum, but increased dopamine metabolite levels in the NAcc and VTA. Our results suggest a novel role for PREP in the modulation of dopaminergic transmission, which may be different in nigrostriatal and mesolimbic pathways.

Effects of drugs on the formation of 3-methoxytyramine, a dopamine metabolite, in the substantia nigra, striatum, nucleus accumbens and tuberculum olfactorium of the rat.

Abstract 3-Methoxytyramine (3-MT) was assayed with a sensitive and rapid liquid chromatographic separation on a Sephadex G 10 column in combination with a fluorimetric detection in a continuous flow system. The method made it possible to measure pargyline-induced 3-MT concentrations in various regions of a single rat brain. After haloperidol, morphine or sulpiride treatment, pargyline-induced 3-MT concentrations in the striatum, nucleus accumbens, tuberculum olfactorium and substantia nigra of the rat were comparable with reported changes of homovanillic acid concentrations. Dose-response curves for 3-MT increase in various brain regions after (+)-amphetamine pretreatment were studied. The effect of (+)-amphetamine on 3-MT formation was much more pronounced in nerve terminal areas, especially in the mesolimbic structures. The influence of apomorphine, γ-hydroxybutyric acid, haloperidol, reserpine or combined treatment of haloperidol and (+)-amphetamine revealed pronounced differences on regional 3-MT concentrations, indicating important differences between the regulation of dopamine metabolism in the substantia nigra and nerve terminal areas.

1H, 13C and 15N resonance assignments of the human mesencephalic astrocyte-derived neurotrophic factor

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease, where dopaminergic cells die most prominently in the area of substantia nigra. Neurotrophic factors (NTFs) are secreted proteins, which upon binding to their target receptors trigger survival pathways to prevent neuronal loss. Recently discovered NTFs mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF) most efficiently protect and repair the dopaminergic neurons in the animal 6-OHDA models of PD. However, the neuroprotective mechanism of MANF/CDNF is currently elusive. To this end, we have employed high-resolution NMR spectroscopy to determine three-dimensional structure of full-length human MANF in solution and characterized C-terminal domain as structural unit of MANF protein.

Structural abnormality of the substantia nigra in children with attention-deficit hyperactivity disorder

Structural abnormality of the substantia nigra can be detected by transcranial sonography in neuropsychiatric disorders such as Parkinson disease and restless legs syndrome. We investigated echogenicity of the substantia nigra as a potential structural marker for dysfunction of the nigrostriatal dopamine system in children with attention-deficit hyperactivity disorder (ADHD). We used a blinded design and determined echogenicity of the substantia nigra by use of transcranial sonography in 22 children with ADHD and 22 healthy controls matched for age and sex. The echogenic substantia nigra area was significantly larger in ADHD patients than in healthy controls (F(1,42) = 9.298, p = 0.004, effect size = 0.92). We found no effects of age or sex. Owing to a lack of dimensional assessment, we could not analyze the correlation between echogenicity and clinical symptoms. Our results support the hypothesis that the nigrostriatal dopaminergic system is abnormal in children with ADHD.

Response of neural precursor cells in the brain of Parkinson's disease mouse model after LIF administration

Objective: To access the response of endogenous neural precursor cells (NPCs) in the area of substantia nigra (SN) in the mouse model of Parkinson's disease (PD). To evaluate whether leukemia inhibitory factor (LIF) can up-regulate the expression of NPCs and their fate in differentiation.Methods: NPCs were measured and the number and density were estimated using the confocal counting system in normal control (CON), normal control LIF treated (CON + LIF), PD (PD) and LIF treated PD (PD + LIF) mice.Results: The PD + LIF group showed a statistically significant improvement in the number and density of NPCs compared with PD group, and NPCs are rarely seen in CON and CON + LIF groups.Conclusion: LIF may be a useful treatment for PD by up-regulating the re-expression of NPCs, which may represent the neuroprotection mechanism of LIF.