Studies on Parkinson’s-Disease-Linked Genes, Brain Urea Levels and Histopathology in Rotenone Induced Parkinson’s Disease Rat Model

Kavuri, Suchitra; Sivanesan, S.; Howell, Mathew D.; Rajagopalan, Vijayaraghavan; Jayakumar, R.

doi:10.4236/wjns.2020.104021

Cited by 10 publications

(7 citation statements)

References 64 publications

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“…The blood-brain barrier (BBB) is impermeable to urea; hence, increased brain urea levels in the present study indicate either increased synthesis of brain urea inside the central nervous system or breakage of BBB 54 . A similar experimental study on PD also suggests increased brain urea in Wistar rats induced with rotenone 37 .…”

Section: Urea Changes In Thementioning

confidence: 55%

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Untitled

2023

IJPSR

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Parkinson's disease has been a challenging neurodegenerative disorder for researchers and clinicians alike for decades. Though L-dopa has changed the management of PD to a considerable extent, effective solutions remain elusive since L-dopa, after a few years, partly loses its efficacy and develops dyskinesias as a complication, incapacitating the patient. Also, existing PD animal models using MPTP, rotenone, paraquet, etc cause significant suffering to the animals and also require a minimum of 22-25 days for induction. Hence, a better PD animal model was conceived considering the synergistic oxidative stress lipids, and rotenone induce on striatal neurons. The experiment compared the existing rotenone induction with combined rotenone and high-fat diet induction, carefully watching for motor and behavioural symptoms of PD in the Wistar rats in addition to measuring the biochemical profiles for toxicity, strictly following the ARRIVE guidelines for animal research. This study found that using HFD+Rot for induction not only shortened the duration of induction to a mean of 14 days but also reduced the suffering by reducing the number of intraperitoneal injections needed without significant derangement of safety biochemical parameters. This study also proves the effectiveness by demonstrating the reduced dopamine, serotonin levels in striatal neurons and increased oxidative stress parameters. To the best of our knowledge, no animal study shows a better PD model with all the neurobehavioural and biochemical features of PD with less time for induction. This new HFD+Rot model can therefore be employed to test therapeutics and neurobehavioural studies.

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Section: Urea Changes In Thementioning

confidence: 55%

“…36 . Current evidence suggests that intraperitoneally administered rotenone induces PD much earlier and efficiently with less mortality than orally administered rotenone does 37 .…”

Section: Fig 4: Comparative Effect Of High-fat Diet (Hfd) Rotenone (R...mentioning

confidence: 99%

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2023

IJPSR

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“…Based on our preliminary published results, Kavuri et al, 2020 [21] , it was found that Rot-3-ip induction for 21 days in Wistar rats showed signi icant upregulation of α-synuclein expression (Immuno-histochemistry) with Lewy bodies in brain striatum; whereas Rot-50-po treatment for 28 days in rats caused a moderate increase of α-synuclein with no detectable Lewy bodies. The brain sections from the control groups showed normal architecture.…”

Section: Discussionmentioning

confidence: 83%

A comparative study of neurobehavioral changes induced by rotenone through oral and intraperitoneal administration

Kavuri¹,

Sivanesan²

2022

Int. J. Res. Pharm. Sci.

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Parkinson’s disease is one of the major neurological disorders seen worldwide and associated with many motor and nonmotor symptoms. Rotenone-induced motor and behavior impairments could involve the gut-brain axis which is emphasized in several recent works. To explore how oral and intraperitoneal rotenone toxicity impacts neurobehavioral alterations in Wistar rats. The effect of intraperitoneal (3 mg/kg body weight 21 days) and oral (50 mg/kg body weight for 28 days) rotenone toxicity in male Wistar rats on various neurobehavioral parameters viz., rotarod, actophotometer, rearing behavior and elevated plus maze was comparatively studied. The neurobehavioral studies such as the Rota-rod test, rearing behavior, Elevated plus maze (EPM), and Actophotometer were performed by following standard published protocols and by utilizing the facilities available at the Institution. Kruskal-Wallis one- way ANOVA on ranks with Student-Newman-Keul’s multiple comparisons was used. It was found that both oral and intraperitoneal rotenone treatments had a significant impact on neurobehavioral parameters when compared to their respective controls. Although there were few differences observed in the study set behavioral parameters between intraperitoneal and oral rotenone treatments, it was not significant. The study findings suggest that neurobehavioral alterations caused by oral or intraperitoneal rotenone toxicity are found to be significant. The fact that oral rotenone toxicity has gut-brain axis- related problems can also have a role in PD-related motor/movement and anxiety behavior dysfunctions.

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“…MTs exert various functions, such as in organelle and protein trafficking, cellular differentiation, cargo transport, and motility [ 190 , 191 ]. For a long time now, oxidative stress has been a major and constant culprit in PD pathogenesis, and this has been supported by several postmortem studies in PD brains showing increased levels of oxidative proteins, lipids and nucleic acids [ 192 – 196 ], as well as in studies of genetic or toxin-induced PD models[ 197 – 201 ]. In non-neuronal cells, researchers found that oxidative stress affects MT dynamics by hindering tubulin polymerization and hence affects its stability [ 202 – 204 ].…”

Section: Mt Acetylation Status In Pdmentioning

confidence: 99%

Microtubule acetylation dyshomeostasis in Parkinson’s disease

Naren

Samim

Tryphena

et al. 2023

Transl Neurodegener

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The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule (MT)-mediated axonal transport system. This mechanistically regulated system delivers cargos (proteins, mRNAs and organelles such as mitochondria) back and forth from the soma to the synapse. Motor proteins like kinesins and dynein mechanistically regulate polarized anterograde (from the soma to the synapse) and retrograde (from the synapse to the soma) commute of the cargos, respectively. Proficient axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications (PTMs) of α- and β-tubulin heterodimers, core components constructing the MTs. Occurring within the lumen of MTs, K40 acetylation of α-tubulin via α-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible, which in turn promotes their lifespan. The movement of various motor proteins, including kinesin-1 (responsible for axonal mitochondrial commute), is enhanced by this PTM, and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions, including Alzheimer’s disease and Parkinson’s disease (PD). PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation levels. Although the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question, our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in PD. The enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly explored. Moving towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it. Graphical abstract

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Studies on Parkinson’s-Disease-Linked Genes, Brain Urea Levels and Histopathology in Rotenone Induced Parkinson’s Disease Rat Model

Cited by 10 publications

References 64 publications

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A comparative study of neurobehavioral changes induced by rotenone through oral and intraperitoneal administration

Microtubule acetylation dyshomeostasis in Parkinson’s disease

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