Age and Parkinson’s Disease-Related Neuronal Death in the Substantia Nigra Pars Compacta

Eriksen, Nina; Stark, A.K.; Pakkenberg, Bente

doi:10.1007/978-3-211-92660-4_16

Cited by 24 publications

(25 citation statements)

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“…These observations, along with our current data, suggest that age-associated declines in nigral DA neurons (Eriksen et al, 2009; Fearnley and Lees, 1991; Fox et al, 2001; Morgan et al, 1987) and motor functions (Allen et al, 2011; Bennett et al, 1996; Boger et al, 2006; Irwin et al, 1994; Yue et al, 2012) could be a consequence of decreased ERK5 activation resulting from reduced NTF signaling. It may also be noteworthy that inhibition of the ERK5 pathway has been shown to reduce GDNF mRNA and protein levels in some cells (Obara et al, 2011), suggesting a feedback loop in which MEK5-ERK5 signaling is further decreased.…”

Section: Discussionsupporting

confidence: 73%

“…Loss of motor functions and PD are associated with an age-related loss of nigral DA neurons (Eriksen et al, 2009; Fearnley and Lees, 1991; Fox et al, 2001; Morgan et al, 1987) and/or dysfunction in the nigrostriatal dopaminergic pathways (Carlsson and Winblad 1976; Gerhardt et al, 1995; Irwin et al 1994; McGeer et al, 1977; Yue et al, 2012; Yurek et al, 1998). These DA neuronal impairments may be associated with the age-related decreases in ERK5 activation observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

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The role of ERK1, 2, and 5 in dopamine neuron survival during aging

Parmar

Jaumotte

Wyrostek

et al. 2014

Neurobiology of Aging

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The extracellular signal-regulated kinases (ERKs) 1, 2, and 5 have been shown to play distinct roles in proliferation, differentiation, and neuronal viability. In this study, we examined ERK1, 2, and 5 expression and activation in the substantia nigra (SN), striatum (STR), and ventral tegmental area (VTA) during aging. An age-related decrease in phosphorylated ERK5 was observed in the SN and STR, whereas an increase in total ERK1 was observed in all three regions. In primary cultures of the SN and VTA, inhibition of ERK5 but not ERK1 and 2 significantly decreased DA neuronal viability. These data suggest that ERK5 is essential for the basal survival of SN and VTA dopaminergic neurons. These are the first studies to examine ERK1, 2, and 5 expression and activation in the SN, STR, and VTA during aging and the relative roles of ERK1, 2, and 5 in basal survival of SN and VTA dopaminergic neurons. These data raise the possibility that a decline ERK5 signaling may play a role in age-related impairments in dopaminergic function.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

Parmar

Jaumotte

Wyrostek

et al. 2014

Neurobiology of Aging

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“…One important piece of evidence for this conclusion comes from studies of Parkinson's disease (PD). In that condition, many of the motor deficits are strongly correlated with the loss of the DA neurons of the nigrostriatal projection [5]. …”

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confidence: 99%

L-DOPA reverses motor deficits associated with normal aging in mice

Allen

Carlson

Zigmond

et al. 2011

Neuroscience Letters

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We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling. KeywordsBehavior; dopamine; striatum Aging is usually accompanied by a decline in motor function, a phenomenon that can be observed in laboratory animals as well as in humans. For example, rodents typically exhibit a decline in spontaneous motor activity and motor coordination [1][2][3]7]. Such motor functions appear to be heavily influenced by the dopamine (DA) system [17]. One important piece of evidence for this conclusion comes from studies of Parkinson's disease (PD). In that condition, many of the motor deficits are strongly correlated with the loss of the DA neurons of the nigrostriatal projection [5].Corresponding author: Dr. Jane E. Cavanaugh, Department of Pharmacology, 455 Mellon Hall, Duquesne University, Phone: (412) 396-6358, Fax: (412) 396-4660, cavanaughj@duq.edu. * The first two authors contributed equally to this work.a) The authors have no actual or potential conflicts of interest. b) All animals were maintained in temperature-controlled rooms in the barrier facility maintained by the Division of Laboratory Animal Resources (DLAR) at the University of Pittsburgh. Animals were housed in accordance with Guidelines for the Care and Use of Animals, at 23°C with lights on between 1900 and 0700 hr. Animals were fed and watered ad libitum, and the woodchips in their cages changed every other day. Full-time trained animal care personnel performed all animal handling and maintenance. The director of the DLAR, a trained veterinarian, supervised animal care. All animal care was overseen by the Institutional Animal Care and Use Committee (IACUC).Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. L-DOPA, which increases the availability of DA in striatum, is able to temporarily impr...

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“…26,29,30 The PD models of nonhuman primates have behavioral, neuroanatomical and age-related impairments correspondent with the symptoms of PD patients. 31,32 Chronic MPTP-induced monkey models of PD also show dopaminergic cell loss, α-synuclein aggregation, α-synuclein upregulation, and neuritic α-synuclein pathology. 29,30,33 Comparisons to neuropathological data show that the MPTP-induced dopaminergic neuronal cell death in monkeys is also identical to that observed in PD.…”

Section: Neurotoxin Models 6-hydroxydopaminementioning

confidence: 99%

Animal models of Parkinson's disease and their applications

Park

Zhao²,

Lee

2016

JPRLS

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Abstract:Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs mainly due to the degeneration of dopaminergic neuronal cells in the substantia nigra. l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective known therapy for PD. However, chronic l-DOPA administration results in a loss of drug efficacy and irreversible adverse effects, including l-DOPA-induced dyskinesia, affective disorders, and cognitive function disorders. To study the motor and non-motor symptomatic dysfunctions in PD, neurotoxin and genetic animal models of PD have been widely applied. However, these animal models do not exhibit all of the pathophysiological symptoms of PD. Regardless, neurotoxin rat and mouse models of PD have been commonly used in the development of bioactive components from natural herbal medicines. Here, the main animal models of PD and their applications have been introduced in order to aid the development of therapeutic and adjuvant agents.

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Age and Parkinson’s Disease-Related Neuronal Death in the Substantia Nigra Pars Compacta

Cited by 24 publications

References 100 publications

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

L-DOPA reverses motor deficits associated with normal aging in mice

Animal models of Parkinson's disease and their applications

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Age and Parkinson’s Disease-Related Neuronal Death in the Substantia Nigra Pars Compacta

Cited by 24 publications

References 100 publications

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

L-DOPA reverses motor deficits associated with normal aging in mice

Animal models of Parkinson&#39;s disease and their applications

Contact Info

Product

Resources

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Animal models of Parkinson's disease and their applications