Alterations in the motor cortical and striatal glutamatergic system and d-serine levels in the bilateral 6-hydroxydopamine rat model for Parkinson's disease

Arfani, Anissa El; Albertini, Giulia; Bentea, Eduard; Demuyser, Thomas; Eeckhaut, Ann Van; Smolders, Ilse Julia; Massie, Ann

doi:10.1016/j.neuint.2015.07.005

Cited by 28 publications

(17 citation statements)

References 60 publications

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“…These result in an increase in intracellular Ca 2+ levels, and lead to the destruction of cytoskeleton and degenerate neurons, which is also an important pathologic feature of PD. 34,35 In our study, quantitative analysis of the content of NAA and Glu in the striatum by MRS showed that the content of NAA in the model group decreased and the content of Glu increased. After continuous administration of baicalin for 8 weeks, the content of baicalin significantly changed, indicating that baicalin may play a role by targeting to NAA and Glu.…”

Section: Discussionsupporting

confidence: 54%

<p>Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA</p>

Tu¹,

Wu²,

Yang³

et al. 2020

NDT

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Objective: This research was aimed to investigate the effects of baicalin on 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD) and the main mechanism of baicalin based on metabolomics.Methods: The rat model of PD was induced by 6-OHDA. The protective effects of baicalin on rat model of PD were evaluated by open field test and rotarod test. The anti-PD efficacy of baicalin was evaluated by examining the morphologic changes of neurons and the level of monoamine neurotransmitters in the striatum, the number and morphology of tyrosine hydroxylase (TH)-positive neurons, and oxidative stress. Combined with metabolomics methods, the pharmacodynamic mechanism of baicalin on PD pathogenesis was also explored. Results: Baicalin treatment improved the rod time and voluntary movement in rat model of PD (P<0.05) by the open field test and rotarod test. In addition, baicalin also protected from oxidative stress injury (P<0.05), and regulated the content of monoamine neurotransmitters dopamine, 3,4-dihydroxyphenylacetic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid (P<0.05) and the number and morphology of TH-positive cells in 6-OHDA-induced PD model rats. By metabolomics, multivariate statistical analysis, and receiver operating characteristic curve analysis, we found that two metabolites N-acetyl aspartic acid and glutamic acid had a good diagnostic value. Quantitative analysis of metabolites showed a regulatory function of baicalin. Conclusion: Baicalin has significant protective effect on 6-OHDA-induced PD rats, which may play a protective role through an antioxidant, promoting the release of neurotransmitters and regulating the metabolism of N-acetyl aspartate and glutamate.

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Section: Discussionsupporting

confidence: 54%

<p>Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA</p>

Tu¹,

Wu²,

Yang³

et al. 2020

NDT

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“…Initially, we thought that within patients LRRK2-G2019S alone leads to increased serine levels as observed in NESCs. Increased serine levels were, for instance, previously reported in the striatum of 6-OHDa leasioned rats [27] and serine inversly correlates with PD progression, suggesting that it might inhere a compensatory mechanism [28]. This view, however, was challenged in our data by the discrepancy that gene-correcting LRRK2-G2019S within the patient genetic background did not rescue phenotypes, meaning that other succeptibility factors contribute to phenotype manifestation.…”

Section: Discussioncontrasting

confidence: 47%

Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patients

Nickels

Walter

Bolognin

et al. 2019

Parkinsonism & Related Disorders

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Parkinson's disease (PD) is a multifactorial disorder with complex etiology. The most prevalent PD associated mutation, LRRK2-G2019S is linked to familial and sporadic cases. Based on the multitude of genetic predispositions in PD and the incomplete penetrance of LRRK2-G2019S, we hypothesize that modifiers in the patients' genetic background act as susceptibility factors for developing PD. To assess LRRK2-G2019S modifiers, we used human induced pluripotent stem cell-derived neuroepithelial stem cells (NESCs). Isogenic controls distinguish between LRRK2-G2019S dependent and independent cellular phenotypes. LRRK2-G2019S patient and healthy mutagenized lines showed altered NESC self-renewal and viability, as well as impaired serine metabolism. In patient cells, phenotypes were only partly LRRK2-G2019S dependent, suggesting a significant contribution of the genetic background. In this context we identified the gene serine racemase (SRR) as a novel patient-specific, developmental, genetic modifier contributing to the aberrant phenotypes. Its enzymatic product, D-serine, rescued altered cellular phenotypes. Susceptibility factors in the genetic background, such as SRR, could be new targets for early PD diagnosis and treatment.

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“…Some studies reported that GLAST protein expression is significantly decreased in the striatum at 1 week and 2 weeks after 6-hydroxydopamine (6-OHDA) lesion [ 11 , 61 ]. Besides, GLAST mRNA expression is also decreased in the 6-OHDA lesion rats [ 41 ].…”

Section: Excitotoxicity In the Pathogenesis Of Parkinson's Diseasementioning

confidence: 99%

Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

Zhang

Tan

et al. 2016

Neural Plasticity

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Parkinson's disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.

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Alterations in the motor cortical and striatal glutamatergic system and d-serine levels in the bilateral 6-hydroxydopamine rat model for Parkinson's disease

Cited by 28 publications

References 60 publications

<p>Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA</p>

<p>Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA</p>

Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patients

Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

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