Cholinergic circuit genes in the healthy brain are differentially expressed in regions that exhibit gray matter loss in Parkinson’s disease

AbstractStructural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance. In Parkinson’s disease, the posterior cingulate network and anterior cingulate network showed decreased gray matter and therefore we examined the underlying molecular processes of these anatomical networks in the healthy brain. Whole brain transcriptomics from post-mortem samples from healthy adults, revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS signaling pathways in these PD-related regions. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a protective role. Furthermore, both networks were associated with memory and neuropsychiatric disorders that overlap with Parkinson’s disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson’s disease.

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The Protective Role of Brain CYP2J in Parkinson’s Disease Models

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2917981 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Yueran Li ◽

Jinhua Wu ◽

Xuming Yu ◽

Shufang Na ◽

Ke Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Regions ◽

Protective Role ◽

Neural Cells ◽

Endogenous Substrates ◽

6 Hydroxydopamine ◽

Myd88 Signaling ◽

Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

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Side of motor onset is associated with hemisphere-specific memory decline and lateralized gray matter loss in Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2015.02.008 ◽

2015 ◽

Vol 21 (5) ◽

pp. 465-470 ◽

Cited By ~ 18

Author(s):

Eun-Young Lee ◽

Suman Sen ◽

Paul J. Eslinger ◽

Daymond Wagner ◽

Lan Kong ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

Memory Decline ◽

Specific Memory ◽

Gray Matter Loss ◽

Motor Onset

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Depressive symptoms in Parkinson’s disease are related to decreased left hippocampal volume: correlation with the 15-item shortened version of the Geriatric Depression Scale

Acta Radiologica ◽

10.1177/0284185117719100 ◽

2017 ◽

Vol 59 (3) ◽

pp. 341-345 ◽

Cited By ~ 4

Author(s):

Masami Goto ◽

Koji Kamagata ◽

Taku Hatano ◽

Nobutaka Hattori ◽

Osamu Abe ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gray Matter ◽

Gray Matter Volume ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Hippocampal Volume ◽

Geriatric Depression ◽

Matter Volume ◽

The Relationship

Background The relationship between hippocampal and amygdaloid volumes and depression in patients with Parkinson’s disease (PD) is a controversial issue. Purpose To investigate the correlation between the 15-item shortened version of the Geriatric Depression Scale (GDS-15) and gray matter volume in PD. Material and Methods In the present study, 46 participants with PD were scanned with 3 T magnetic resonance imaging (MRI) to obtain three-dimensional (3D) T1-weighted (T1W) images. Neurologists specializing in movement disorders performed clinical evaluations of the participants (e.g. GDS-15, Mini-Mental State Examination, PD duration, age, sex). Statistical Parametric Mapping 8 software was used for image gray matter segmentation and for a correlation analysis between gray matter volume and GDS-15 score. Results The results showed a significant negative correlation between GDS-15 score and left hippocampal volume, and between GDS-15 score and right parahippocampal gyrus volume. No significant positive correlations were found in the whole brain. Conclusion The current results provide new evidence regarding the relationship between depression in PD and hippocampal volume.

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Reduced lateral occipital gray matter volume is associated with physical frailty and cognitive impairment in Parkinson’s disease

European Radiology ◽

10.1007/s00330-018-5855-7 ◽

2018 ◽

Vol 29 (5) ◽

pp. 2659-2668 ◽

Cited By ~ 5

Author(s):

Yueh-Sheng Chen ◽

Hsiu-Ling Chen ◽

Cheng-Hsien Lu ◽

Meng-Hsiang Chen ◽

Kun-Hsien Chou ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Gray Matter ◽

Gray Matter Volume ◽

Physical Frailty ◽

Matter Volume

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Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

Psychological Medicine ◽

10.1017/s0033291714000348 ◽

2014 ◽

Vol 44 (13) ◽

pp. 2833-2843 ◽

Cited By ~ 52

Author(s):

C. A. Webb ◽

M. Weber ◽

E. A. Mundy ◽

W. D. S. Killgore

Keyword(s):

Depressive Symptoms ◽

Gray Matter ◽

Orbitofrontal Cortex ◽

Gray Matter Volume ◽

Superior Temporal Gyrus ◽

Brain Regions ◽

Anterior Cingulate ◽

Dimensional Approach ◽

Matter Volume ◽

Conjunction Analysis

BackgroundStudies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD)v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.MethodTo examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants.ResultsThe severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression.ConclusionsReduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

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Voxel-based meta-analysis of gray matter volume reductions associated with cognitive impairment in Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-016-8122-3 ◽

2016 ◽

Vol 263 (6) ◽

pp. 1178-1187 ◽

Cited By ~ 20

Author(s):

Yaqian Xu ◽

Jing Yang ◽

Xinyu Hu ◽

Huifang Shang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Gray Matter ◽

Meta Analysis ◽

Gray Matter Volume ◽

Matter Volume

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S159. SUBCORTICAL GRAY MATTER VOLUME IS ASSOCIATED WITH SCHIZOPHRENIA AND WITH BOTH ITS FAMILIAL AND CLINICAL RISK

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.225 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S96-S97

Author(s):

Roberta Passiatore ◽

Linda A Antonucci ◽

Leonardo Fazio ◽

Barbara Gelao ◽

Andrea Falsetti ◽

...

Keyword(s):

Gray Matter ◽

Gray Matter Volume ◽

Familial Risk ◽

Structural Features ◽

Brain Regions ◽

Anterior Cingulate ◽

Group Differences ◽

Intracranial Volume ◽

Significant Group ◽

Clinical Risk

Abstract Background Patients with schizophrenia (SCZ) show lower volumetric estimates of gray matter (GM) than healthy controls (HC). Similar results have been reported in healthy siblings of patients (SIB). However, it is unclear whether this phenotype is also present in individuals at clinical high-risk (CHR), characterized by sub-threshold symptoms and loss of functioning. We hypothesized that GM volumetric differences are associated with both familial and clinical risk for schizophrenia Methods We processed the T1-weighted MRI scans acquired at 3 Tesla of 544 HC, 63 SIB, 20 CHR and 120 SCZ using CAT12. We used ANCOVA to assess group differences (HC vs. CHR vs. SIB vs. SCZ), with linear and quadratic age, gender and total intracranial volume as nuisance covariates. We assessed the reproducibility of our case/control findings in an independent sample of 127 HC and 36 SCZ. Group differences were tested post hoc through Fisher’s test. Results We found significant group effects in the bilateral thalamus, bilateral hippocampus and anterior cingulate (FWE<0.05). Specifically, SCZ presented the lowest GM volume in these regions compared to the other three groups, with SIB and CHR’s GM estimates intermediate between HC and SCZ (p<0.05). The associations with schizophrenia were replicated in the independent validation sample. Discussion Individuals with familial or clinical risk for schizophrenia have lower GM estimates in the same brain regions. These findings, suggest that these structural features are not only associated with familial risk for schizophrenia but that they are also associated with its sub-threshold symptoms.

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Vascular Inflammation Is a Risk Factor Associated with Brain Atrophy and Disease Severity in Parkinson’s Disease: A Case-Control Study

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2591248 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Chiun-Chieh Yu ◽

Hsiu-Ling Chen ◽

Meng-Hsiang Chen ◽

Cheng-Hsien Lu ◽

Nai-Wen Tsai ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Gray Matter ◽

Vascular Inflammation ◽

Gray Matter Volume ◽

Statistical Parametric Mapping ◽

Clinical Disease ◽

Matter Volume ◽

Gray Matter Atrophy

Introduction. Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. Objective. Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. Methods. Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. Results. The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. Conclusion. Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.

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