Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

Mabandla, Musa V.; Nyoka, Mpumelelo; Daniels, Willie M. U.

doi:10.1016/j.brainres.2015.06.017

Cited by 20 publications

(14 citation statements)

References 54 publications

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“…Our results showed significant alleviation of striatal dopamine level following B[a]P administration and the result finds support from previous report [ 20 ]. Similarly, 6-OHDA administration leads to significant decrease in dopamine level as compared to B[a]P and the above findings are in agreement with previous report [ 34 , 35 ]. The possible effect of neonatal B[a]P administration on striatal dopamine level during adolescence was found to be linked with the effect of 6-OHDA.…”

Section: Discussionsupporting

confidence: 93%

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

Das

Patel

Patri

2016

Journal of Toxicology

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Exposure to persistent genotoxicants like benzo[a]pyrene (B[a]P) during postnatal days causes neurobehavioral changes in animal models. However, neurotoxic potential of B[a]P and its association with 6-hydroxydopamine (6-OHDA) induced neurobehavioral changes are yet to be explored. The growth of rat brain peaks at the first week of birth and continues up to one month with the attainment of adolescence. Hence, the present study was conducted on male Wistar rats at postnatal day 5 (PND 5) following single intracisternal administration of B[a]P to compare with neurobehavioral and neurotransmitter changes induced by 6-OHDA at PND 30. Spontaneous motor activity was significantly increased by 6-OHDA showing similar trend following B[a]P administration. Total distance travelled in novel open field arena and elevated plus maze was significantly increased following B[a]P and 6-OHDA administration. Neurotransmitter estimation showed significant alleviation of dopamine in striatum following B[a]P and 6-OHDA administration. Histopathological studies of striatum by hematoxylin and eosin (H&E) staining revealed the neurodegenerative potential of B[a]P and 6-OHDA. Our results indicate that B[a]P-induced spontaneous motor hyperactivity in rats showed symptomatic similarities with 6-OHDA. In conclusion, early postnatal exposure to B[a]P in rats causing neurobehavioral changes may lead to serious neurodegenerative consequences during adolescence.

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Section: Discussionsupporting

confidence: 93%

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

Das

Patel

Patri

2016

Journal of Toxicology

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“…6‐OHDA lesion of the nigrostriatal DA pathway produces denervation of the striatum resulting in DA deficiency in the striatum (Mabandla and Russell, 2010; Mpofana et al, 2014; Huot et al, 2015). DA concentration in the striatum was significantly decreased in MS rats compared to NS rats suggesting that maternal separation exacerbated DA depletion in agreement with previous studies (Mpofana et al, 2014; Mabandla et al, 2015). The results further showed that striatal DA loss was attenuated by FM (MS compared to MSPr‐F rats) suggesting a neuroprotective capability of FM on DA neurons, a novel finding.…”

Section: Discussionsupporting

confidence: 92%

“…The test and procedure used were similar to published tests (Schallert and Tillerson, 2000; Woodlee et al, 2008; Mabandla et al, 2015). Briefly, the animal is held by its torso with its hindquarters elevated from the surface of the table such that the animal only supports its weight with the forelimb that is tested.…”

Section: Methodsmentioning

confidence: 99%

Anti‐parkinsonian effects of fluvoxamine maleate in maternally separated rats

Dallé¹,

Daniels²,

Mabandla³

2016

Intl J of Devlp Neuroscience

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Exposure to early life stress has been shown to result in anxiety-like symptoms and exacerbates degeneration of dopaminergic neurons in a rat model of Parkinson's disease (PD). First line treatment for anxiety disorders includes the use of Fluvoxamine maleate (FM). In this study, we investigated whether treating anxiety-like symptoms with FM has an effect in alleviating the neurotoxic effects of 6-OHDA in a parkinsonian rat model. Early maternal separation was used to create a rat model that depicts anxiety-like symptoms. Maternally separated adult Sprague-Dawley rats were treated with FM prior to and following lesion with 6-hydroxydopamine (6-OHDA). The elevated plus-maze (EPM) and the forelimb akinesia tests were used to evaluate anxiety-like symptoms and motor impairment respectively. Blood plasma was used to measure corticosterone concentration, and striatal tissue was collected for dopamine (DA) and serotonin (5-HT) analysis. Our results show that animals exposed to early life stress displayed increased anxiety-like symptoms and elevated basal plasma corticosterone concentration which were attenuated by treatment with FM. A 6-OHDA lesion effect was evidenced by impairment in the forelimb akinesia test as well as decreased DA and 5-HT concentrations in the lesioned striatum. These effects were attenuated on DA neurons by FM treatment in the pre-lesion treated as opposed to the post-lesion treated rats. This study suggests that early treatment of anxiety-like behavior decreases the vulnerability of DA neurons to neurotoxic insults later in life thus slowing down DA degeneration in PD.

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“…Our explanation resembles that of the stepping test. For the execution of the voluntary forelimb movements a normal DA content of the CPu is essential (Salamone et al, 1993; Shi et al, 2004; Manfredsson et al, 2007; Woodlee et al, 2008; Plowman et al, 2011; Fleming et al, 2013; Mabandla et al, 2015). BoNT-A did not improve left forelimb use as it could increase DA concentration.…”

Section: Discussionmentioning

confidence: 99%

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Antipova

Holzmann

Schmitt

et al. 2017

Front. Behav. Neurosci.

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Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions. We hypothesized that the interhemispheric differences of acetylcholine (ACh) concentration seen in unilateral hemi-PD should be differentially and temporally influenced by the ipsilateral or contralateral injection of BoNT-A. Hemi-PD rats were injected with 1 ng BoNT-A or vehicle substance into either the ipsilateral or contralateral striatum 6 weeks after 6-OHDA-lesion and various behaviors were tested. In hemi-PD rats intrastriatal ipsilateral BoNT-A-injections significantly reduced apomorphine-induced rotations and increased amphetamine-induced rotations, but showed no significant improvement of forelimb usage and akinesia, lateralized sensorimotor integration and also no effect on spontaneous locomotor activity. However, intrastriatal BoNT-A-injections contralateral to the lesion led to a significant increase of the apomorphine-induced turning rate only 2 weeks after the treatment. The apomorphine-induced rotation rate decreases thereafter to a value below the initial rotation rate. Amphetamine-induced rotations were not significantly changed after BoNT-A-application in comparison to sham-treated animals. Forelimb usage was temporally improved by contralateral BoNT-A-injection at 2 weeks after BoNT-A. Akinesia and lateralized sensorimotor integration were also improved, but contralateral BoNT-A-injection had no significant effect on spontaneous locomotor activity. These long-ranging and different effects suggest that intrastriatally applied BoNT-A acts not only as an inhibitor of ACh release but also has long-lasting impact on transmitter expression and thereby on the basal ganglia circuitry. Evaluation of changes of transmitter receptors is subject of ongoing studies of our group.

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Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

Cited by 20 publications

References 54 publications

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

Anti‐parkinsonian effects of fluvoxamine maleate in maternally separated rats

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

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