Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway

Renaud, Jean‐François; Bassareo, Valentina; Beaulieu, Jimmy; Pinna, Annalisa; Schlich, Michele; Lavoie, Claude; Murtas, Daniela; Simola, Nicola; Martinoli, Maria-Grazia

doi:10.1016/j.neurobiolaging.2018.05.010

Cited by 42 publications

(57 citation statements)

References 57 publications

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“…gene. In agreement with previous studies, 46,47 both STZ-treated and db/db mice exhibited increased vulnerability to nigrostriatal neurodegeneration. We now show that increased vulnerability in both types of diabetic animals is associated with decreased levels of proteins regulating dopamine neurotransmission and with altered stimulus-dependent striatal dopamine release.…”

Section: I a B E T E Ssupporting

confidence: 93%

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

et al. 2020

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Background Numerous studies indicate an association between neurodegenerative and metabolic diseases. Although still a matter of debate, growing evidence from epidemiological and animal studies indicate that preexisting diabetes increases the risk to develop Parkinson's disease. However, the mechanisms of such an association are unknown. Objectives We investigated whether diabetes alters striatal dopamine neurotransmission and assessed the vulnerability of nigrostriatal neurons to neurodegeneration. Methods We used streptozotocin‐treated and genetically diabetic db/db mice. Expression of oxidative stress and nigrostriatal neuronal markers and levels of dopamine and its metabolites were monitored. Dopamine release and uptake were assessed using fast‐scan cyclic voltammetry. 6‐Hydroxydopamine was unilaterally injected into the striatum using stereotaxic surgery. Motor performance was scored using specific tests. Results Diabetes resulted in oxidative stress and decreased levels of dopamine and its metabolites in the striatum. Levels of proteins regulating dopamine release and uptake, including the dopamine transporter, the Girk2 potassium channel, the vesicular monoamine transporter 2, and the presynaptic vesicle protein synaptobrevin‐2, were decreased in diabetic mice. Electrically evoked levels of extracellular dopamine in the striatum were enhanced, and altered dopamine uptake was observed. Striatal microinjections of a subthreshold dose of the neurotoxin 6‐hydroxydopamine in diabetic mice, insufficient to cause motor alterations in nondiabetic animals, resulted in motor impairment, higher loss of striatal dopaminergic axons, and decreased neuronal cell bodies in the substantia nigra. Conclusions Our results indicate that diabetes promotes striatal oxidative stress, alters dopamine neurotransmission, and increases vulnerability to neurodegenerative damage leading to motor impairment. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: I a B E T E Ssupporting

confidence: 93%

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

et al. 2020

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“…One study found that thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of reactive oxygen species elimination, regulates Parkin/PINK1-mediated mitophagy in dopaminergic neurons under high-glucose conditions ( Su et al, 2020 ), which revealed the neuronal impact of mitochondrial dysfunction caused by hyperglycemia and hyperglycemia-induced oxidative stress. In addition, the preferential occurrence of nigrostriatal dopaminergic neurodegeneration in long-term hyperglycemia suggests that hyperglycemia causes premature aging of the central nervous system, fostering the development of age-related neurodegenerative diseases ( Renaud et al, 2018 ). However, these studies did not sufficiently clarify the molecular link between hyperglycemia and PD.…”

Section: Molecular Genetics Cell Biology and Epidemiology: Correlatmentioning

confidence: 99%

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

et al. 2020

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Diabetes mellitus (DM) and Parkinson’s disease (PD) have been and will continue to be two common chronic diseases globally that are difficult to diagnose during the prodromal phase. Current molecular genetics, cell biological, and epidemiological evidences have shown the correlation between PD and DM. PD shares the same pathogenesis pathways and pathological factors with DM. In addition, β-cell reduction, which can cause hyperglycemia, is a striking feature of DM. Recent studies indicated that hyperglycemia is highly relevant to the pathologic changes in PD. However, further correlation between DM and PD remains to be investigated. Intriguingly, polycystic monoamine transporter 2 (VMAT2), which is co-expressed in dopaminergic neurons and β cells, is responsible for taking up dopamine into the presynaptic vesicles and can specifically bind to the β cells. Furthermore, we have summarized the specific molecular and diagnostic functions of VMAT2 for the two diseases reported in this review. Therefore, VMAT2 can be applied as a target probe for positron emission tomography (PET) imaging to detect β-cell and dopamine level changes, which can contribute to the diagnosis of DM and PD during the prodromal phase. Targeting VMAT2 with the molecular probe 18 F-FP-(+)-DTBZ can be an entry point for the β cell mass (BCM) changes in DM at the molecular level, to clarify the potential relationship between DM and PD. VMAT2 has promising clinical significance in investigating the pathogenesis, early diagnosis, and treatment evaluation of the two diseases.

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“…A hyperglykaemia számos korábbi klinikai vizsgálatban bizonyítottan befolyásolta az újszülöttek pszichomotoros és idegrendszeri fejlődését [49][50][51], valamint állatkísérletes körülmények között sejthalált okozó hatása van [52,53]. Állatmodell segítségével igazolták a hosszú távú hyperglykaemiás állapot hatását a nigrostriatalis motoros útvonalra, melynek eredménye a dopaminerg idegsejtek degenerációja, továbbá felvetették a kapcsolat lehetőségét a Parkinson-szerű tünettan kialakulásával is [54].…”

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Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késői szövődményei

et al. 2019

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Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270–1278.

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Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway

Cited by 42 publications

References 57 publications

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késői szövődményei

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