Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia

Ribeiro, Renata Pietsch; Santos, Danúbia Bonfanti; Colle, Dirleise; Naime, Aline Aita; Gonçalves, Cinara L.; Ghizoni, Heloisa; Hort, Mariana Appel; Godoi, Marcelo; Dias, Paulo Fernando; Braga, Antônio L.; Farina, Marcelo

doi:10.1016/j.bbr.2016.02.023

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…Peculiarly, since Macrod2 KO mice were determined to be hyperactive (total distance travelled in a variety of testing paradigms) their natural walk, as recorded by the catwalk test (in the dark, least stressful), was actually slower and with shorter steps. This type of gait is known as bradykinesia (a slow shuffling gait as appears in Parkinson’s disease [ 75 ]). Males are possibly more affected than the females, however the trend is present in both sexes.…”

Section: Resultsmentioning

confidence: 99%

Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice

Crawford

Oliver

Agnew

et al. 2021

Cells

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Adenosine diphosphate ribosylation (ADP-ribosylation; ADPr), the addition of ADP-ribose moieties onto proteins and nucleic acids, is a highly conserved modification involved in a wide range of cellular functions, from viral defence, DNA damage response (DDR), metabolism, carcinogenesis and neurobiology. Here we study MACROD1 and MACROD2 (mono-ADP-ribosylhydrolases 1 and 2), two of the least well-understood ADPr-mono-hydrolases. MACROD1 has been reported to be largely localized to the mitochondria, while the MACROD2 genomic locus has been associated with various neurological conditions such as autism, attention deficit hyperactivity disorder (ADHD) and schizophrenia; yet the potential significance of disrupting these proteins in the context of mammalian behaviour is unknown. Therefore, here we analysed both Macrod1 and Macrod2 gene knockout (KO) mouse models in a battery of well-defined, spontaneous behavioural testing paradigms. Loss of Macrod1 resulted in a female-specific motor-coordination defect, whereas Macrod2 disruption was associated with hyperactivity that became more pronounced with age, in combination with a bradykinesia-like gait. These data reveal new insights into the importance of ADPr-mono-hydrolases in aspects of behaviour associated with both mitochondrial and neuropsychiatric disorders.

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Section: Resultsmentioning

confidence: 99%

Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice

Crawford

Oliver

Agnew

et al. 2021

Cells

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“…They examined the 6-OHDA lesion range by assessing the adjusting step test and the forelimb use asymmetry test on the 5th day after the lesion and found that lesioned rats affected with a right paw for less than 5% of movements in both the step test and the asymmetry test [ 88 ]. Ribeiro et al (2016) showed that the low dose of 6-OHDA (40 µg/site, intracerebroventricular injection) affect the striatal biochemical parameters that correlated to oxidative stress and produced forelimb inability in male Swiss mice [ 89 ]. Their experiments showed that 6-OHDA dose (40 µg/site) exhibited neither hypokinesia nor reduced forelimb strength, produced bradykinesia, and the succinobucol restored the bradykinesia by decreasing the forelimb ability without changes in locomotion [ 89 ].…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

“…Ribeiro et al (2016) showed that the low dose of 6-OHDA (40 µg/site, intracerebroventricular injection) affect the striatal biochemical parameters that correlated to oxidative stress and produced forelimb inability in male Swiss mice [ 89 ]. Their experiments showed that 6-OHDA dose (40 µg/site) exhibited neither hypokinesia nor reduced forelimb strength, produced bradykinesia, and the succinobucol restored the bradykinesia by decreasing the forelimb ability without changes in locomotion [ 89 ]. Lai et al (2019) used three doses of 5/10/15 µg of 6-OHDA in 4 µL (in saline) and intracranially injected into right midforebrain injection to induce the lesion in male Sprague Dawley rats.…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

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“…In our present experiment, chronic EA treatment ameliorated gross motor signs (ambulatory activity and coordinated balance ability) and ne forelimb motor performance in a partial-lesioned model. In details, the partial lesion in the striatum was su cient to trigger de cits of motor skills, such as the reduction of movement and the slow execution of movements [34], cardinal features of PD observed during the early stage. EA mitigated the striatal lesion and behavioral de cits in a closely correlated manner.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, unilateral injection of 6-OHDA into the MFB at a low dose (3 µg) caused mild motor de cits, including forelimb akinesia in the stepping test [8]. Intracerebroventrical infusion of 6-OHDA induced forelimb grasping inability in mice, which was assessed as an earlier motor sign and accepted as bradykinesia in PD [34]. Consistent with these ndings, our partially lesioned mice with 6-OHDA showed impaired motor skills, including reduced movement distance and shortened latency time.…”

Section: Discussionmentioning

confidence: 99%

Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

Su¹,

Yu²,

Li³

et al. 2020

Preprint

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Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

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Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia

Cited by 8 publications

References 40 publications

Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice

Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

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