Striatal trophic factor activity in aging monkeys with unilateral MPTP-induced parkinsonism

Collier, Timothy J.; Ling, Zaodung; Carvey, Paul M.; Fletcher-Turner, Anita; Yurek, David M.; Sladek, John R.; Kordower, Jeffrey H.

doi:10.1016/j.expneurol.2004.08.018

Cited by 74 publications

(64 citation statements)

References 49 publications

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“…We demonstrated that aged animals respond to MPTP-induced lesion with more severe striatal TH protein decline, and that this age effect is greater in males than females. Our results are consistent with the previous reports and show that female mice are less susceptible to MPTP intoxication than their male counterparts [28,29] . We also found, in accordance with others [25,30,31] , that in young mice striatal TH content recovered at later time points.…”

Section: Discussionsupporting

confidence: 83%

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Ciesielska

Joniec

Kurkowska‐Jastrzębska

et al. 2007

Neuroimmunomodulation

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Objective: The neuroinflammatory reaction has been linked with Parkinson’s disease. One of the hypotheses to explain the significance of age and gender (male predominance) effects on neurodegeneration in Parkinson’s disease may result from a link between these risk factors and the inflammatory processes. Here, we investigated the expression of inflammatory mediators in relation to 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-induced neurodegenerative processes in nigrostriatal pathway in young and aged male and female mice.Methods and Results: We simultaneously assessed striatal tyrosine hydroxylase (TH) protein concentrations (Western blotting) and cytokine (TNFα, IFNγ, IL-1β, IL-6 and TGFβ₁) mRNA levels (RT-PCR) in young and aged (2- and 12-month-old) C57BL/6 male and female mice after 6 h, 1, 3, 7, 14, 21 days after MPTP intoxication.Western blotting analysis showed that at the early time points, males showed a greater reduction in striatal TH versus females. Additionally, in contrast to the aged mice, in young males and females the TH concentration gradually increased between the 7th and the 21st day after intoxication. The increases in TNFα, IL-1β and IFNγ after intoxication were faster in both young and aged males than females. In males (both ages), we observed an increase in TGFβ₁ at the early time points. In contrast, in females (both ages) TGFβ₁ was elevated at later time points. MPTP caused an increase in IL-6 in males and females, but this increase was significantly higher in females. Conclusions: A gender and age skewing of the cytokine gene expression in the striatum after intoxication may be related to the greater susceptibility in males as well as older animals to the detrimental effects of MPTP.

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Section: Discussionsupporting

confidence: 83%

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Ciesielska

Joniec

Kurkowska‐Jastrzębska

et al. 2007

Neuroimmunomodulation

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“…In the striatum, an increase in GDNF mRNA or protein levels has been observed after 6-OHDA-induced (Zhou et al, 2000;Nakajima et al, 2001;FletcherTurner, 2001, 2002;Hida et al, 2003) or MPTP-induced injury (Tang et al, 1998). However, other authors have failed to detect changes in striatal GDNF levels after 6-OHDA lesion (Stromberg et al, 1993;Anastasia et al, 2007) or MPTP treatment (Inoue et al, 1999;Collier et al, 2005). These conflicting results might arise from differences in the injury models and protocols, or different time points analysed.…”

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 70%

“…Moreover, the neurotrophic response to injury depends on the age of the animals. In general, young animals show a greater capacity to up-regulate neurotrophic factors (Yurek and Fletcher-Turner, 2001;Collier et al, 2005).…”

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 99%

Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

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“…These progressive losses in the two models may have Brownell where a single toxin was administered numerous times, no single hit study we are aware of has probeen more pronounced had we extended the protocols until the animals were older, given that compensatory duced progression. In contrast, the synergistic losses seen following multiple hits and our preliminary indicaprocesses are markedly attenuated in aged animals (19).…”

Section: The Multiple Hit Hypothesis Of Pdmentioning

confidence: 80%

Progressive Dopamine Neuron Loss in Parkinson's Disease: The Multiple Hit Hypothesis

2006

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Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD-or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD. We then evaluate the primary issue of the progressive loss of DA neurons, which, except for a few studies, has not been addressed in animal models of PD, even though this is the major pathological characteristic of the disease. Lastly, we discuss the possibility that more than one risk factor for PD may be necessary to develop an animal model that shows synergy-the progressive loss of DA neurons. Thus, the multiple hit hypothesis of PD-that is, the effect of more then one risk factor-may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans. Key words: Parkinson's disease Dopamine neurons Progression Multiple hit hypothesis PARKINSON'S DISEASEwith an estimated 50-60% loss of DA neurons in the substantia nigra pars compacta (SNpc) (2,26,81). Idiopathic PD generally develops after the age of 60. HowJames Parkinson first systematically described the symptoms of Parkinson's disease (PD) in the early ever, patients younger than 40 years of age have been identified, and many have been shown to have one of 1800s, which he labeled the "shaking palsy." The cardinal features of PD are tremor, rigidity, brady-/akinesis, several genetic mutations, suggesting that early onset PD may be familial (18,41,69,88). PD is a progressive and postural instability. Approximately 40,000 people in the US are diagnosed with PD every day, and over 1 neurodegenerative disease. When first diagnosed, most patients exhibit mild unilateral symptoms that inexoramillion Americans have this disease. The daily cost is estimated at $66 million, including direct and indirect bly progress to bilateral debilitating signs and symptoms that require full-time nursing care in late-stage disease. costs such as the inability to work and medical/longterm care (75). PD is the second most prevalent neuroTo date there is no proven strategy to stop or slow the progression of PD. However, significant advancements degenerative disease next to Alzheimer's disease. No cure currently exists.in alleviating the symptoms of PD using drug therapy and surgical procedures have evolved. The most widely The symptoms of...

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Striatal trophic factor activity in aging monkeys with unilateral MPTP-induced parkinsonism

Cited by 74 publications

References 49 publications

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease

Driving GDNF expression: The green and the red traffic lights

Progressive Dopamine Neuron Loss in Parkinson's Disease: The Multiple Hit Hypothesis

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