Stress‐induced neurological impairments in an animal model of parkinsonism

Snyder, Abigail M.; Stricker, Edward M.; Zigmond, Michael J.

doi:10.1002/ana.410180506

Cited by 117 publications

(58 citation statements)

References 31 publications

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“…However, studies have also shown that the presentation of stressors to these seemingly recovered animals often results in sustained neurological impairments (Stricker and Zigmond 1974;Snyder et al 1985).…”

Section: Discussionmentioning

confidence: 98%

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders

Pienaar

Kellaway

Russell

et al. 2008

Stress

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Many studies have shown that early life stress may lead to impaired brain development, and may be a risk factor for developing psychiatric pathologies such as depression. However, few studies have investigated the impact that early life stress might have on the onset and development of neurodegenerative disorders, such as Parkinson's disease, which is characterized in part by the degeneration of dopaminergic neurons in the nigrostriatal pathway. The present study subjected rat pups to a maternal separation paradigm that has been shown to model adverse early life events, and investigated the effects that it has on motor deficits induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12 microg/4 microl). The female rats were assessed for behavioral changes at 28 days post-lesion with a battery of tests that are sensitive to the degree of dopamine loss. The results showed that rats that had been subjected to maternal separation display significantly impaired performance in the vibrissae and single-limb akinesia test when compared to normally reared animals. In addition, there was a significant increase in the loss of tyrosine hydroxylase staining in maternally separated rats. Our results therefore suggest that adverse experiences sustained during early life contribute to making dopamine neurons more susceptible to subsequent insults occurring during more mature stages of life and may therefore play a role in the etiopathogenesis of Parkinson's disease.

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Section: Discussionmentioning

confidence: 98%

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders

Pienaar

Kellaway

Russell

et al. 2008

Stress

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show abstract

“…PD symptoms in patients are often acutely exacerbated by infection, inflammation, cold, fever and mental stress (30)(31)(32)(33). With decreased energy producing capability, these situations may induce energy disturbance and subsequent energy crisis, which would exacerbated their PD symptoms and cause further damage to the sensitive DA cells.…”

Section: Discussionmentioning

confidence: 99%

Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

Bai

Tang³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is characterized by the hallmark feature of loss of dopaminergic neurons in the substantia nigra. Energy metabolic disorder is associated with the pathogenesis of PD; however, the development of this disorder is yet to be elucidated. PD-like characteristics have been demonstrated in a rotenone rat model. In the present study, energy metabolism status was investigated in a rat model following intraperitoneal treatment with 1.0 mg/kg rotenone every 48 h. The behavior and tyrosine hydroxylase-positive levels in the substantia nigra of rats that were treated with rotenone for 24 weeks demonstrated that these rats developed more severe parkinsonism, as compared with that were treated for 16 weeks. Detection of ATP, lactic acid, NADH dehydrogenase 1 mRNA and lactate dehydrogenase B mRNA levels in the ventral mesocerebrum (VM) and skeletal muscle (SM) of the rats that had been treated with rotenone for 16 and 24 weeks demonstrated that the energy stress induced by rotenone progressed in both VM and SM. Notably, the energy stress detected in VM was more severe, and this energy stress was decompensated in the VM of rats that had been treated with rotenone for 24 weeks. The progression of energy stress and the incidence of energy decompensation in VM may be important for the improvement of PD pathology. IntroductionParkinson's disease (PD) is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra. PD is the most common neurodegenerative movement disorder, affecting >1% of the population that are aged >60 (1). Current treatments, such as pharmaceutical agents or deep brain stimulation predominantly target the symptoms and are unable to attenuate or reverse the progression of this disease (2). Understanding PD at a cellular and molecular level is important to determine novel targets and develop neuroprotective and disease-modifying therapeutic strategies. Although the causes and potential factors remain unknown, environmental factors may have a critical role, such as herbicides or pesticides, organic solvents, carbon monoxide and carbon disulfide (3,4). Notably, various studies have suggested that PD is associated with energy metabolism defects (5-7).Due to their structure, physiologic activities and high oxidative level of DA metabolism, DA cells in the substantia nigra are energy demanding and prone to energy stress (8). Furthermore, these cells have a relative low capacity for glycolysis compensation and lower glutathione levels (9,10), which ensures that they cannot respond appropriately to energy stress and are thus sensitive to energy disturbances.Rotenone is a common insecticide and mitochondria complex 1 inhibitor, which is used to induce chronic rotenone rat models with PD-associated features that manifest as DA cells are selectively damaged (11). However, how energy stress is induced and associated with the development of PD-associated in this model remains unknown.In the present study, rats were ...

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“…This behavioral task evaluates skilled forepaw reaching [2], motor sequencing, posture and balance. The integrity of the nigrostriatal system is determined using biochemical measurement of DA and its metabolites [3,4]. Striatal DA receptors may show shifts in expression following partial DA denervation, as they do in other unilateral animal models of PD [5][6][7].…”

Section: Subject Termsmentioning

confidence: 99%

Degenerative Risks for Parkinson's Disease After Toxin Exposure and Stress

Ariano¹

2002

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Stress‐induced neurological impairments in an animal model of parkinsonism

Cited by 117 publications

References 31 publications

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders

Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

Degenerative Risks for Parkinson's Disease After Toxin Exposure and Stress

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