The aging striatal dopamine function

Darbin, Olivier

doi:10.1016/j.parkreldis.2011.11.025

Cited by 69 publications

(50 citation statements)

References 88 publications

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“…According to the epidemiological studies, PD is rare before 50 years old and the prevalence increases with age, reaching 4 % in individuals over 85 years old (de Lau and Breteler 2006). Aging itself could cause declined striatal DA function (Darbin 2012;Haycock et al 2003;Kaasinen and Rinne 2002;Rinne et al 1990;Wang et al 1998) and PD-like nigral pathology (Buchman et al 2012;Jellinger 2004;Rudow et al 2008). In a study of 744 elderly individuals without PD, nigral pathology was present in 39 % of the participants and especially, a combination of neuronal loss and Lewy bodies was observed in 10 % of the cases (Buchman et al 2012).…”

Section: G2019s Lrrk2 Confers Higher Vulnerability To Lactacystin-indmentioning

confidence: 99%

G2019S LRRK2 and aging confer susceptibility to proteasome inhibitor-induced neurotoxicity in nigrostriatal dopaminergic system

Xiao

Yang

2015

J Neural Transm

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The leucine-rich repeat kinase 2 (LRRK2) mutation G2019S is one of the most common genetic causes in Parkinson's disease (PD). The penetrance of G2019S LRRK2 is incomplete and is age-dependent, therefore, it has been speculated that environmental toxins and aging could contribute to G2019S LRRK2-related PD pathogenesis. To prove this speculation, we performed a longitudinal investigation in mice bearing G2019S LRRK2 mutation. BAC G2019S LRRK2 transgenic (Tg) mice and their wildtype (Wt) littermates were treated with lactacystin, a specific proteasome inhibitor. The susceptibilities of mice to lactacystin-induced nigrostriatal dopaminergic (DAergic) degeneration were evaluated, at 5 and 12 months of age. We found that lactacystin treatment caused a greater decline of striatal DA content in the Tg mice at either 5 or 12 months of age than their age-matched Wt littermates. Moreover, the lactacystin-treated Tg or Wt mice at 12 months of age lose much more nigral tyrosine hydroxylase (TH)-positive neurons than the mice at 5 months of age, indicating an age-associated DAergic neurotoxicity. Additionally, stereotactic injection of lactacystin induced a dramatic increase of activated microglia in substantia nigra of mice at 12 months of age, compared with mice at 5 months of age. In summary, our study suggests that expression of the G2019S mutation in the mouse LRRK2 gene confers an age-associated high susceptibility to proteasome inhibition-induced nigrostriatal DAergic degeneration.

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Section: G2019s Lrrk2 Confers Higher Vulnerability To Lactacystin-indmentioning

confidence: 99%

G2019S LRRK2 and aging confer susceptibility to proteasome inhibitor-induced neurotoxicity in nigrostriatal dopaminergic system

Xiao

Yang

2015

J Neural Transm

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“…Usually, the presence of both cardinal motor dysfunction and response to levodopa are features that support a diagnosis of PD. In this procedure, one of the challenges is to distinguish typical PD from the atypical parkinsonism (Darbin 2012), such as agerelated parkinsonism or multiple system atrophy. That is because some of the cardinal signs of parkinsonism are not usually specific to PD.…”

Section: Introductionmentioning

confidence: 99%

“…That is because some of the cardinal signs of parkinsonism are not usually specific to PD. Especially, the motor symptoms are very easily confused with the bodily functions of normal aging, i.e., age-related parkinsonism (Darbin 2012;Kalia and Lang 2015;Valls-Solé and Valldeoriola 2002;Jankovic 2008;Savitt et al 2006;Miller and O'Callaghan 2015). This makes an accurate diagnosis of PD difficult, particularly in the early stages of PD.…”

Section: Introductionmentioning

confidence: 99%

Complexity of resting-state EEG activity in the patients with early-stage Parkinson’s disease

Wang

Deng

et al. 2016

Cogn Neurodyn

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To investigate the abnormal brain activities in the early stage of Parkinson's disease (PD), the electroencephalogram (EEG) signals were recorded with 20 channels from non-dementia PD patients (18 patients, 8 females) and age matched healthy controls (18 subjects, 8 females) during the resting state. Two methods based on the ordinal patterns of the recorded series, i.e., permutation entropy (PE) and order index (OI), were introduced to characterize the complexity of the cortical activities for two groups. It was observed that the resting-state EEG of PD patients showed lower PE and higher OI than healthy controls, which indicated that the early-stage PD caused the reduced complexity of EEG. We further applied two methods to determine the complexity of EEG rhythms in five sub-bands. The results showed that the gamma, beta and alpha rhythms of PD patients were characterized by lower PE and higher OI, i.e., reduced complexity, than healthy subjects. No significant differences were observed in theta or delta rhythms between two groups. The findings suggested that PE and OI were promising methods to detect the abnormal changes in the dynamics of EEG signals associated with early-stage PD. Further, such changes in EEG complexity may be the early markers of the cortical or subcortical dysfunction caused by PD.

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“…Rather, they are associated with a wide range of adverse health outcomes including an increased risk of death and the development of disability, mild cognitive impairment, Alzheimer's disease and cognitive decline (Buchman et al, 2012). Furthermore, dopaminergic replacement therapies, in contrast to their use in PD, are ineffective at relieving the burden associated with age-related parkinsonism (for a review, see Darbin, 2012). …”

Section: Introductionmentioning

confidence: 99%

“…Because the primary cause of PD is the degeneration of the nigrostriatal dopaminergic system (Hornykiewicz and Kish, 1987), there has long been a suspicion that the mechanisms underlying motor decline in normal aging also involve the central dopaminergic system (for a review, see Darbin, 2012). Although the movement disorders seen with advancing age resemble those seen in PD, it is still not clear whether similar changes in the CNS circuitry underlie these similar behavioral impairments.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease–related from age-related changes in basal ganglia function

Andersen

Hardy

Forman

et al. 2015

Neurobiology of Aging

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The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. While the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, three groups of rhesus macaques were studied: Normal middle-aged animals (used as controls), middle-aged animals with MPTP-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and phMRI procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine (APO) administration followed by either a D1 (SCH23390) or D2 (raclopride) receptor antagonist. Significant, functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these two groups in the internal segment of the globus pallidus (GPi). In contrast, the pharmacological responses seen in the control animals were much milder compared with the other two groups in all examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain.

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The aging striatal dopamine function

Cited by 69 publications

References 88 publications

G2019S LRRK2 and aging confer susceptibility to proteasome inhibitor-induced neurotoxicity in nigrostriatal dopaminergic system

G2019S LRRK2 and aging confer susceptibility to proteasome inhibitor-induced neurotoxicity in nigrostriatal dopaminergic system

Complexity of resting-state EEG activity in the patients with early-stage Parkinson’s disease

Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease–related from age-related changes in basal ganglia function

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