Alterations in [3H]spiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy-Drager syndrome and Parkinson's disease

1979 ◽  
Vol 43 (3) ◽  
pp. 429-437 ◽  
Author(s):  
M. Quik ◽  
G. Spokes ◽  
A.V.P. Mackay ◽  
R. Bannister
Brain ◽  
2017 ◽  
Vol 140 (9) ◽  
pp. 2460-2474 ◽  
Author(s):  
Junchao Tong ◽  
Gausiha Rathitharan ◽  
Jeffrey H Meyer ◽  
Yoshiaki Furukawa ◽  
Lee-Cyn Ang ◽  
...  

Abstract See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article.  The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA, respectively) are drug targets in the treatment of Parkinson’s disease. Inhibitors of MAOB are used clinically in Parkinson’s disease for symptomatic purposes whereas the potential disease-modifying effect of monoamine oxidase inhibitors is debated. As astroglial cells express high levels of MAOB, the enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular process possibly involved in Parkinson’s disease pathogenesis as elevation of MAOB in astrocytes might be harmful. Since brain monoamine oxidase status in Parkinson’s disease is uncertain, our objective was to measure, by quantitative immunoblotting in autopsied brain homogenates, protein levels of both monoamine oxidases in three different degenerative parkinsonian disorders: Parkinson’s disease (n = 11), multiple system atrophy (n = 11), and progressive supranuclear palsy (n = 16) and in matched controls (n = 16). We hypothesized that if MAOB is ‘substantially’ localized to astroglial cells, MAOB levels should be generally associated with standard astroglial protein measures (e.g. glial fibrillary acidic protein). MAOB levels were increased in degenerating putamen (+83%) and substantia nigra (+10%, non-significant) in multiple system atrophy; in caudate (+26%), putamen (+27%), frontal cortex (+31%) and substantia nigra (+23%) of progressive supranuclear palsy; and in frontal cortex (+33%), but not in substantia nigra of Parkinson’s disease, a region we previously reported no increase in astrocyte protein markers. Although the magnitude of MAOB increase was less than those of standard astrocytic markers, significant positive correlations were observed amongst the astrocyte proteins and MAOB. Despite suggestions that MAOA (versus MAOB) is primarily responsible for metabolism of dopamine in dopamine neurons, there was no loss of the enzyme in the parkinsonian substantia nigra; instead, increased nigral levels of a MAOA fragment and ‘turnover’ of the enzyme were observed in the conditions. Our findings provide support that MAOB might serve as a biochemical imaging marker, albeit not entirely specific, for astrocyte activation in human brain. The observation that MAOB protein concentration is generally increased in degenerating brain areas in multiple system atrophy (especially putamen) and in progressive supranuclear palsy, but not in the nigra in Parkinson’s disease, also distinguishes astrocyte behaviour in Parkinson’s disease from that in the two ‘Parkinson-plus’ conditions. The question remains whether suppression of either MAOB in astrocytes or MAOA in dopamine neurons might influence progression of the parkinsonian disorders.


2019 ◽  
Vol 11 (2) ◽  
pp. 30-36
Author(s):  
A. G. Trufanov ◽  
A. A. Yurin ◽  
A. B. Buriak ◽  
S. A. Sandalov ◽  
M. M. Odinak ◽  
...  

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and the first one among the nosological entities of parkinsonism. Susceptibility-weighted imaging (SWI), magnetic resonance imaging (MRI) pulse sequence, which allows the in vivo estimation of the values of iron deposition in different areas of the brain, is a potential technique for the early diagnosis of PD and for the study of the pathogenesis of its complications.Objective: to compare the values of iron deposition in the basal ganglia in Stages II and III PD and to determine the relationship of clinical findings to the level of iron deposition according to the SWI findings.Patients and methods. Twenty-four patients with Hoehn and Yahr Stages II (n=24) and III (n=12) PD were examined. All the patients underwent brain MRI on a Siemens TrioTim (3T) MRI scanner by using pulse sequences T1, T2, SWI and subsequently quantifying the iron deposition (SPIN software). The accumulation of iron is visualized as an area of reduced signal intensity on SWI, and its estimation in accordance with the SPIN program has accordingly a smaller value. The regions of interest on both sides were the dentate nucleus, substantia nigra, red nucleus, putamen, globus pallidus, and head of the caudate nucleus. The examination protocol also included tests using the following scales: the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Examination (MMSE), Frontal Assessment Batter (FAB), Freezing of Gait (FOG), Gait and Balance Scale (GABS), the Epworth Daytime Sleepiness Scale, the Parkinson's Disease Quality of Life Questionnaire (PDQ), the Beck Depression Inventory, and the Clock-Drawing Test.Results and discussion. The investigators found significant (p<0.05) correlations between the clinical picture and the level of iron deposition in the regions of interest in patients with Stage II PD: FOG – left caudate nucleus (r=-0.94); GABS – left caudate nucleus (r=-0.94); and in patients with stage III of the disease: UPDRS (full) – left red nucleus (r=-0.82), right globus pallidus (r=-0,80), left putamen (r=-0,96); UPDRS (Section 2) – left red nucleus (r=-0.77), left globus pallidus (r=-0.84); UPDRS (Section 3) – right putamen (r=-0,85), right globus pallidus (r=-0.78), left globus pallidus (r=-0,92); FOG – left globus pallidus (r=-0.81); GABS – left red nucleus (r=-0.96), left putamen (r=0.82), right putamen (r=-0.89), left globus pallidus (r=-0.82), right globus pallidus (r=-0.85), left caudate nucleus (r=-0.82), right caudate nucleus (r=-0.89); Beck Depression Inventory – right substantia nigra (r=-0.82).Conclusion. SWI measurement of the values of iron deposition in the structures of the extrapyramidal system in PD provides an additional insight into the pathological processes occurring in them.


Author(s):  
Ryan J. Uitti ◽  
A.H. Rajput ◽  
B. Rozdilsky ◽  
M. Bickis ◽  
T. Wollin ◽  
...  

ABSTRACT:Metal deficiency or toxicity states have been recognized as a cause of several neurological disorders and are suspected in others. We analyzed four brain regions (frontal cortex, caudate nucleus, substantia nigra, and cerebellum) in 36 human brains for concentrations of 24 metals (Ag, Al, As, B, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Pb, Mg, Mn, Mo, Na, Ni, P, Se, Ti, V, W, Zn). Regional metal concentrations, measured using atomic absorption and atomic emission spectroscopy, were compared between 9 Parkinson's disease (PD) brains, 15 brains from patients with other chronic neurological diseases, and 12 control brains. No significant metal concentration differences were noted between brains from PD and other chronic neurologic disease. However, parkinsonian brains (PD and parkinsonism secondary to neurofibrillary tangle disease) showed lower concentrations of magnesium in the caudate nucleus and copper in the substantia nigra than control brains. These findings may represent an etiologically important clue to parkinsonism.


2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
C Funke ◽  
A Soehn ◽  
C Schulte ◽  
M Bonin ◽  
C Klein ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document