Diabetes Mellitus to Neurodegenerative Disorders: Is Oxidative Stress Fueling the Flame?

Mule, Nandkishor; Singh, Jai Vir

doi:10.2174/1871527317666180809092359

Cited by 31 publications

(14 citation statements)

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“…28,58,59 Because of the relatively high-energy demands that they require for function, 44,60 nigrostriatal dopaminergic neurons are particularly vulnerable to oxidative stress, [61][62][63] which, in turn, is thought to play an important role in PD. 44,64,65 Notably, 6-OHDA used at a subthreshold dose did not produce detectable motor impairment in nondiabetic animals despite significant decreases in TH (42%) and DAT (36%) in the striatum, in line with previous studies. [66][67][68][69] In contrast, motor deficits were present 2 weeks after the onset of diabetes in STZ-treated mice showing a loss of 50% (TH) and 47% (DAT).…”

Section: I a B E T E Ssupporting

confidence: 89%

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: 89%

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

et al. 2020

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“…In addition, it has been reported that HDAC3 negatively regulates spatial memory in rodents [41], [42]. One limitation of our study is that although NAD + depletion [43] and increased oxidative stress [44] are the main features of neurodegenerative disorders, we could not examine these variables in this study.…”

Section: Discussionmentioning

confidence: 90%

The effect of silymarin supplementation on cognitive impairment induced by diabetes in rats

Yön

Belviranlı

Okudan

2019

Journal of Basic and Clinical Physiology and Pharmacology

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Background The objective of this investigation was to examine the impact of silymarin supplementation on locomotion, anxiety-related behavior, learning, and memory via several behavioral tests, such as open field, elevated plus maze, and Morris water maze tests in streptozotocin-induced diabetic rats. Methods The rats were divided into the control, diabetes, silymarin, and diabetes plus silymarin groups. On the 30th–35th days of the study, several behavioral tests were performed and blood and brain tissue samples were taken and brain-derived neurotrophic factor (BDNF) and histone deacetylase 3 (HDAC3) levels were analyzed. Results There was no significant difference in locomotor activity between the groups (p = 0.534). Spatial memory was lower (p = 0.000) but anxiety scores were higher (p = 0.005) in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups. Plasma (p = 0.000) and brain tissue (p = 0.007) BDNF levels were lower in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups; however, plasma (p = 0.432) and brain tissue (p = 0.321) HDAC3 levels did not significantly differ between the groups. Conclusions The findings obtained from this study suggest that silymarin supplementation could improve anxiety-related behavior, and learning and memory in diabetic rats by increasing the BDNF levels.

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“…However, food commercialization and the shift toward production of processed and ultra-processed foods have revealed clear adverse effects, such as the identification of processed food as a major cause for over-eating and the increase in the risk of metabolic syndrome, obesity, and diabetes (Hall et al, 2019 ). As the brain is one of the primary energy-demanding organs in the human body, it comes with no surprise that the brain is highly affected by such metabolic disorders as evident by recent epidemiological studies (Beydoun et al, 2008 ; Mule and Singh, 2018 ). For example, type-2 diabetes is strongly associated with cognitive impairment due to insulin resistance and altered glucose availability to neurons, which impair energy production capacity and proper neuronal function (Kandimalla et al, 2017 ).…”

Section: A Blessing and A Cursementioning

confidence: 99%

“…Another possible risk factor of neurodegenerative diseases is high caloric intake and obesity (Luchsinger et al, 2002 ; Beydoun et al, 2008 ). Accumulating evidence indicates that excessive food consumption may be harmful to the brain as continuous high glucose levels may increase oxidative stress, harming the vulnerable aging brain (Mule and Singh, 2018 ).…”

Section: Eating Ourselves Awaymentioning

confidence: 99%

Food and Age: It Takes Two to Degenerate

Nicola

Okun

2020

Front. Aging Neurosci.

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Diabetes Mellitus to Neurodegenerative Disorders: Is Oxidative Stress Fueling the Flame?

Cited by 31 publications

References 0 publications

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice

The effect of silymarin supplementation on cognitive impairment induced by diabetes in rats

Food and Age: It Takes Two to Degenerate

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