Effect of aging on concentrations of D2-receptor-containing neurons in the rat striatum

Zhou, Han; Kuyatt, Brian L.; Kochman, Kazimierz; DeSouza, Errol B.; Roth, George S.

doi:10.1016/0006-8993(89)91108-6

Cited by 97 publications

(29 citation statements)

References 26 publications

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“…This means that the inhibitory basal tonus of dopamine at the CB activity is less marked in old rats, probably resulting from a reduction in the number of receptors throughout aging. This is not an unexpected finding considering that it has previously been found that the density of striatal D 2 -receptors is significantly reduced in aged rats between 30% and 80% depending on the study (Marshall and Joyce 1988;Petkov et al 1988;Han et al 1989;Popoli et al 1998). However, in the CB this reduction is not enough to reduce the effect of exogenous dopamine which has the same magnitude in old rats and controls.…”

Section: Discussionsupporting

confidence: 48%

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Monteiro

Batuca

Obeso

et al. 2010

AGE

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The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A 2 -adenosine receptors stimulation and attenuated by D 2 -dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine and dopamine administration is almost unknown. This study aims to investigate the ventilatory response to ischemia and to adenosine, dopamine, and their antagonists in old rats, as well as the effect of hypoxia on adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation in the aged CB. In vivo experiments were performed on young and aged rats anesthetized with pentobarbitone and breathing spontaneously. CB ischemia was induced AGE (2011) 33:337-350 DOI 10.1007 Scientific knowledge on the subject The functional ventilatory consequences of the morphological and molecular changes in the carotid body observed in aged animals, as well as the ventilatory effects of dopamine and adenosine in old animals, are still unknown.What this study adds to the field The carotid body's peripheral control of ventilation is not impaired by aging. The preservation of the inhibitory and excitatory effects on ventilation caused by exogenous dopamine and adenosine, respectively, should be taken into account in the therapeutic use of these amines and their agonists and antagonists in elderly people. by bilateral common carotid occlusions. cAMP content was measured in CB incubated with different oxygen concentrations. Hyperoxia caused a decrease in cAMP in the CB at all ages, but no differences were found between normoxia and hypoxia or between young and old animals. The endogenous dopaminergic inhibitory tonus is slightly reduced. However, both the ventilation decrease caused by exogenous dopamine and the increase mediated by A 2A -adenosine receptors are not impaired in aged animals. The bradycardia induced by adenosine is attenuated in old rats. The CB's peripheral control of ventilation is preserved during aging. Concerns have also arisen regarding the clinical usage of adenosine to revert supraventricular tachycardia and the use of dopamine in critical care situations involving elderly people.

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Section: Discussionsupporting

confidence: 48%

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Monteiro

Batuca

Obeso

et al. 2010

AGE

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“…This decrement has been observed in rodents, as well as primates including humans (52,53). During aging, D 2 -dopamine (DA) receptor-containing neurons in striatum are decreased about 25-30% (52,54). Although the cause of the neuron death is not well understood, recent evidence suggest that apoptosis may be involved in this process.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Induces Apoptosis through an Oxidation-involved SAPK/JNK Activation Pathway

Luo¹,

Umegaki²,

Wang³

et al. 1998

Journal of Biological Chemistry

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296

187

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Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time-and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys 3 Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAG⌬169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases.

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“…At the molecular level, the biosynthesis of the D 2 R has been shown to be reduced in the aged striatum (Henry and Roth 1984;Henry et al 1987;Norman et al 1987), and the concentration of mRNA for this receptor also decreases with advancing age (Della Vedova et al 1992; Weiss et al 1992). At the cellular level, approximately 20% of the striatal neurons are lost (Han et al 1989). In effect, in the mammalian brain there appears to be about a 30-50% loss of D 2 R in the aged striata.…”

Section: Functional Interactions Between Dopaminergic and Cholinergicmentioning

confidence: 96%

Aging of the striatum: mechanisms and interventions

Umegaki

Roth

Ingram

2008

AGE

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Motor function declines with increasing adult age. Proper regulation of the balance between dopamine (DA) and acetylcholine (ACh) in the striatum has been shown to be fundamentally important for motor control. Although other factors can also contribute to this age-associated decline, a decrease in the concentration and binding potential of the DA D(2) receptor subtype in the striatum, especially in the cholinergic interneurons, are involved in the mechanism. Our studies have shown that gene transfer of the DA D(2) receptor subtype with adenoviral vectors is effective in ameliorating age-associated functional decline of the striatal cholinergic interneurons. These achievements confirm that an age-associated decrease of D(2)R contributes functional alteration of the interaction of DA and ACh in the striatum and demonstrate that these age-associated changes indeed are modifiable.

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Effect of aging on concentrations of D2-receptor-containing neurons in the rat striatum

Cited by 97 publications

References 26 publications

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Dopamine Induces Apoptosis through an Oxidation-involved SAPK/JNK Activation Pathway

Aging of the striatum: mechanisms and interventions

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