Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects

被引:6
作者
Wu, Chenqing [1 ]
Wu, Haoting [1 ]
Zhou, Cheng [1 ]
Guan, Xiaojun [1 ]
Guo, Tao [1 ]
Wu, Jingjing [1 ]
Chen, Jingwen [1 ]
Wen, Jiaqi [1 ]
Qin, Jianmei [1 ]
Tan, Sijia [1 ]
Duanmu, Xiaojie [1 ]
Yuan, Weijin [1 ]
Zheng, Qianshi [1 ]
Zhang, Baorong [2 ]
Xu, Xiaojun [1 ]
Zhang, Minming [1 ,3 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Radiol, Hangzhou, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 2, Dept Radiol, Sch Med, 88 Jiefang Rd, Hangzhou 31009, Peoples R China
基金
中国国家自然科学基金;
关键词
Amplitude of low-frequency fluctuations; Cerebral blood flow; Levodopa therapy; Neurovascular coupling; Parkinson's disease; Molecular mechanism; RESTING-STATE FMRI; CEREBRAL PERFUSION; HEMODYNAMIC-RESPONSE; BASAL GANGLIA; BRAIN; DOPAMINE; CONNECTIVITY; ORGANIZATION; DYSFUNCTION; IMPAIRMENT;
D O I
10.1016/j.nbd.2024.106406
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. Material and methods: A total of 52 drug-na & iuml;ve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-na & iuml;ve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. Results: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. Conclusion: Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.
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页数:9
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共 82 条
  • [1] Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes
    Al-Bachari, Sarah
    Vidyasagar, Rishma
    Emsley, Hedley C. A.
    Parkes, Laura M.
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2017, 37 (10) : 3409 - 3421
  • [2] Acute L-DOPA administration reverses changes in firing pattern and low frequency oscillatory activity in the entopeduncular nucleus from long term L-DOPA treated 6-OHDA-lesioned rats
    Aristieta, A.
    Ruiz-Ortega, J. A.
    Morera-Herreras, T.
    Miguelez, C.
    Ugedo, L.
    [J]. EXPERIMENTAL NEUROLOGY, 2019, 322
  • [3] Developmental coupling of cerebral blood flow and fMRI fluctuations in youth
    Baller, Erica B.
    Valcarcel, Alessandra M.
    Adebimpe, Azeez
    Alexander-Bloch, Aaron
    Cui, Zaixu
    Gur, Ruben C.
    Gur, Raquel E.
    Larsen, Bart L.
    Linn, Kristin A.
    O'Donnell, Carly M.
    Pines, Adam R.
    Raznahan, Armin
    Roalf, David R.
    Sydnor, Valerie J.
    Tapera, Tinashe M.
    Tisdall, M. Dylan
    Vandekar, Simon
    Xia, Cedric H.
    Detre, John A.
    Shinohara, Russell T.
    Satterthwaite, Theodore D.
    [J]. CELL REPORTS, 2022, 38 (13):
  • [4] Cerebrovascular responses to somatomotor stimulation in Parkinson's disease: A multivariate analysis
    Barnes, Sam C.
    Panerai, Ronney B.
    Beishon, Lucy
    Hanby, Martha
    Robinson, Thompson G.
    Haunton, Victoria J.
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2022, 42 (08) : 1547 - 1558
  • [5] Parkinson's disease
    Bloem, Bastiaan R.
    Okun, Michael S.
    Klein, Christine
    [J]. LANCET, 2021, 397 (10291) : 2284 - 2303
  • [6] Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches
    Bohnen, Nicolaas I.
    Yarnall, Alison J.
    Weil, Rimona S.
    Moro, Elena
    Moehle, Mark S.
    Borghammer, Per
    Bedard, Marc-Andre
    Albin, Roger L.
    [J]. LANCET NEUROLOGY, 2022, 21 (04) : 381 - 392
  • [7] The Vasomotor Response to Dopamine Is Altered in the Rat Model of L-dopa-Induced Dyskinesia
    Booth, Samuel
    Ramadan, Abdullah
    Zhang, Dali
    Lu, Lingling
    Kirouac, Gilbert
    Jackson, Michael F.
    Anderson, Chris
    Ko, Ji Hyun
    [J]. MOVEMENT DISORDERS, 2021, 36 (04) : 938 - 947
  • [8] Cortical GABA interneurons in neurovascular coupling: Relays for subcortical vasoactive pathways
    Cauli, B
    Tong, XK
    Rancillac, A
    Serluca, N
    Lambolez, B
    Rossier, J
    Hamel, E
    [J]. JOURNAL OF NEUROSCIENCE, 2004, 24 (41) : 8940 - 8949
  • [9] The precuneus: a review of its functional anatomy and behavioural correlates
    Cavanna, AE
    Trimble, MR
    [J]. BRAIN, 2006, 129 : 564 - 583
  • [10] Dynamics of Top-Down Control and Motor Networks in Parkinson's Disease
    Chen, Li
    Bedard, Patrick
    Hallett, Mark
    Horovitz, Silvina G.
    [J]. MOVEMENT DISORDERS, 2021, 36 (04) : 916 - 926