Increased dopamine synthesis in aging substantia nigra neurons

Greenwood, Carol E.; Tatton, W. G.; Seniuk, Nadine A.; Biddle, Fred G.

doi:10.1016/0197-4580(91)90087-z

Cited by 39 publications

(29 citation statements)

References 25 publications

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“…This cell loss was accompanied with compensatory sprouting and the appearance of dysmorphic and beading neurites, as well as microgliosis, a result congruent with the notion that microglia may induce neuritic beading during neuronal dysfunction (24). Furthermore, findings of compensatory sprouting upon cell loss, dysmorphic neurites, and an increase in proinflammatory responses are all present in postmortem samples from PD patients (25)(26)(27)(28)(29)(30). Therefore, given the early age of onset of degeneration in these mice, our findings are of particular significance and may correlate with features of autosomal recessive PD.…”

Section: Discussionsupporting

confidence: 65%

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Rousseaux

Marcogliese

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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DJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse. A subset of DJ-1–nullizygous mice, when fully backcrossed to a C57BL/6J background, display dramatic early-onset unilateral loss of dopaminergic (DA) neurons in their substantia nigra pars compacta , progressing to bilateral degeneration of the nigrostriatal axis with aging. In addition, these mice exhibit age-dependent bilateral degeneration at the locus ceruleus nucleus and display mild motor behavior deficits at aged time points. These findings effectively recapitulate the early stages of PD. Therefore, the DJ1-C57 mouse provides a tool to study the preclinical aspects of neurodegeneration. Importantly, by exome sequencing, we identify candidate modifying genes that segregate with the phenotype, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice.

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Section: Discussionsupporting

confidence: 65%

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Rousseaux

Marcogliese

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…In awake animals, ing aged neurons to increase transmitter synthesis (Greenwood et al, 1991;Tatton et al, 1991a) and sprout their terminal axons (Tatton et al, 1992) in order to compensate for the death of their fellows. Some peripheral neurons are able to effect axonal regrowth and reinnervate target structures after the loss of their fellows neurons (Himes and Tessler, 1989;Rotshenker, 1988).…”

Section: Potential Functional Consequencesmentioning

confidence: 98%

Age‐related loss of knee joint afferents in mice

Salo

Tatton

1993

J of Neuroscience Research

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Previous work in our laboratory revealed markedly different rates of age-related death of four monoaminergic neuronal populations in the C57BL/6 mouse. Although dorsal root ganglion neurons (DRGns) have been reported not to suffer similar age-related death in rodents, we determined if there is age-related death of the subpopulation of DRGns innervating the knee joints of C57BL/6 mice, which are known to develop degenerative arthritis with aging. The somata of dorsal root ganglion neurons innervating the mouse knee joint (KJ-DRGns) were identified by retrograde tracing with Fluoro-Gold (FG). Lumbar ganglia were serially sectioned and the numbers of FG-labelled KJ-DRGns counted at five ages encompassing the animal's life span. Changes in size of the total population of lumbar DRGns (L-DRGns) were estimated by counting nucleated somata from every fifth toluidine blue-stained serial section from the L3 and L4 lumbar ganglia at three different ages. Using a computer-assisted video morphometric technique somal areas were measured from random sections to determine the distribution of sizes of neurons in the KJ-DRGn and general lumbar DRGn populations at different ages. Counts of FG-labelled joint afferents were 238.5 +/- 80.3 (mean +/- SD) KJ-DRGns per knee at 2 months of age, declining to 103.2 +/- 20.1 by 24 months, representing a 57% loss over the average life span of the C57 mice. The loss occurred in two phases, with a rapid rate over the first 8 months of life and a more moderate rate of loss over the remaining months. L-DRGn numbers revealed a slower overall rate of loss in comparison to the KJ-DRGn population with an average 33.7% loss over the life span of this mouse. Somal size measurements revealed that the larger sizes of KJ-DRGns were lost over the first 8 months of life, with little change in the distribution of somal sizes thereafter. The distributions of sizes of the L-DRGn population did not change significantly over the life spans of the mice. The data provides evidence that the age-related loss of KJ-DRGns is significantly greater than DRGns in general, and may be particularly apparent in the population of larger sized presumed mechanoreceptor neurons. The loss of the KJ-DRGns is approximately reciprocal to the incidence rate of knee joint osteoarthritis reported for the C57BL/6 mice.

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“…There are indications that an increase in DA turnover might be an early compensatory mechanism for DAn degeneration in PD (Barrio et al ., 1990; Rodriguez & Castro, 1991; Sossi et al ., 2002). A similar compensatory mechanism has been proposed for the age-related loss of DAn (Greenwood et al ., 1991). There is evidence suggesting that nsDAn surviving the SN degeneration may present a partial loss of their phenotypic characteristics in the PD (Kastner et al ., 1993; Miller et al ., 1999; Gonzalez-Hernandez et al ., 2001, 2004; Chu et al ., 2006), a fact that could explain why a portion of the melanin-positive SN neurons does not express TH or other dopaminergic markers in PD (Kordower et al ., 2013).…”

Section: Physiological Changes Of Dan In Pd and Agingmentioning

confidence: 99%

Parkinson's disease as a result of aging

et al. 2015

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It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.

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Increased dopamine synthesis in aging substantia nigra neurons

Cited by 39 publications

References 25 publications

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Age‐related loss of knee joint afferents in mice

Parkinson's disease as a result of aging

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