Aging mildly affects dendritic arborisation and synaptic protein expression in human substantia nigra pars compacta

Naskar, Aditi; Mahadevan, Anita; Philip, Mariamma; Alladi, Phalguni Anand

doi:10.1016/j.jchemneu.2019.02.001

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…Rather, aging is associated with alterations at a cellular level that predispose the loss of DA neurons in the SNc, which is considered the cardinal event in the pathogenesis of PD [ 28 ]. Aging results in global changes in plasticity in the central nervous system, but SNc seems to be moderately affected compared to other brain regions [ 29 ]. Nogo-signaling plays a key role in the context of plasticity perturbations, and there is evidence that the expression of this complex signaling system is timely and regionally regulated in aging mice brains [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson’s Disease

Eyer

Santo

Hewer

et al. 2021

Cells

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Parkinson’s disease is mainly characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Together with the small number, the high vulnerability of the dopaminergic neurons is a major pathogenic culprit of Parkinson’s disease. Our previous findings of a higher survival of dopaminergic neurons in the substantia nigra co-expressing Nogo-A in an animal model of Parkinson’s disease suggested that Nogo-A may be associated with dopaminergic neurons resilience against Parkinson’s disease neurodegeneration. In the present study, we have addressed the expression of Nogo-A in the dopaminergic neurons in the substantia nigra in postmortem specimens of diseased and non-diseased subjects of different ages. For this purpose, in a collaborative effort we developed a tissue micro array (TMA) that allows for simultaneous staining of many samples in a single run. Interestingly, and in contrast to the observations gathered during normal aging and in the animal model of Parkinson’s disease, increasing age was significantly associated with a lower co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson’s disease. In sum, while Nogo-A expression in dopaminergic neurons is higher with increasing age, the opposite is the case in Parkinson’s disease. These observations suggest that Nogo-A might play a substantial role in the vulnerability of dopaminergic neurons in Parkinson’s disease.

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Section: Discussionmentioning

confidence: 99%

Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson’s Disease

Eyer

Santo

Hewer

et al. 2021

Cells

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“…In contrast, Asian-Indians with lower PD prevalence (52.7/100,000) (Das et al 2010) had a relatively higher number of SNpc DA neurons with no age-related neuronal loss (Alladi et al 2009). This along with subtle glial, dendritic, and synaptic changes noted in this population (Jyothi et al 2015;Naskar et al 2019) might explain the lower prevalence of PD in them. Thus, DA neuronal numbers and their response to ageing may play a vital role in shaping the individual's vulnerability to develop PD.…”

Section: Introductionmentioning

confidence: 81%

Differences in Neuronal Numbers, Morphology, and Developmental Apoptosis in Mice Nigra Provide Experimental Evidence of Ontogenic Origin of Vulnerability to Parkinson’s Disease

et al. 2021

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Parkinson disease (PD) prevalence varies by ethnicity. In an earlier study, we replicated the reduced vulnerability to PD in an admixed population, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-susceptible C57BL/6 J, MPTP-resistant CD-1 and their F1 crossbreds. In the present study, we investigated if the differences have a developmental origin. Substantia nigra was evaluated at postnatal days 2 (P2), P6, P10, P14, P18, and P22. C57BL/6 J mice had smaller nigra and fewer dopaminergic neurons than the CD-1 and crossbreds at P2, which persisted through development. A significant increase in numbers and nigral volume was observed across strains until P14. A drastic decline thereafter was specific to C57BL/6 J. CD-1 and crossbreds retained their numbers from P14 to stabilize with supernumerary neurons at adulthood. The neuronal size increased gradually to attain adult morphology at P10 in the resistant strains, vis-à-vis at P22 in C57BL/6 J. Accordingly, in comparison to C57BL/6 J, the nigra of CD-1 and reciprocal crossbreds possessed cytomorphological features of resilience, since birth. The considerably lesser dopaminergic neuronal loss in the CD-1 and crossbreds was seen at P2 and P14 and thereafter was complemented by attenuated developmental cell death. The differences in programmed cell death were confirmed by reduced TUNEL labelling, AIF, and caspase-3 expression. GDNF expression aligned with the cell death pattern at P2 and P14 in both nigra and striatum. Earlier maturity of nigra and its neurons appears to be better features that reflect as MPTP resistance at adulthood. Thus, variable MPTP vulnerability in mice and also differential susceptibility to PD in humans may arise early during nigral development.

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“…In contrast, Asian-Indians with lower PD prevalence (52.7/100,000) (Das et al 2010) had relatively higher number of SNpc DA neurons with no age-related neuronal loss (Alladi et al 2009). This along with subtle glial; dendritic and synaptic changes noted in this population (Naskar et al 2019;Jyothi et al 2015) might explain the lower prevalence of PD in them. Thus DA neuronal numbers and their response to aging may play a vital role in shaping the individual's vulnerability to develop PD.…”

mentioning

confidence: 82%

Differences in neuronal numbers, morphology and developmental apoptosis in mice nigra provide experimental evidence of ontogenic origin of vulnerability to Parkinson’s disease

Vidyadhara

Yarreiphang

Raju

et al. 2020

Preprint

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Parkinson disease (PD) prevalence varies by ethnicity. In an earlier study we replicated the reduced vulnerability to PD in an admixed population, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-susceptible C57BL/6J, MPTP-resistant CD-1 and their F1 crossbreds. In the present study we investigated if the differences have a developmental origin. Substantia nigra was evaluated at postnatal days 2 (P2), P6, P10, P14, P18, and P22. C57BL/6J mice had smaller nigra and fewer dopaminergic neurons than the CD-1 and crossbreds at P2, which persisted through development. A significant increase in numbers and nigral volume was observed across strains till P14. A drastic decline thereafter was specific to C57BL/6J. CD-1 and crossbreds retained their numbers from P14 to stabilize with supernumerary neurons at adulthood. The neuronal size increased gradually to attain adult morphology at P10 in the resistant strains, vis-à-vis at P22 in C57BL/6J. Accordingly, in comparison to C57BL/6J, the nigra of CD-1 and reciprocal crossbreds possessed cyto-morphological features of resilience, since birth. The considerably lesser dopaminergic neuronal loss in the CD-1 and crossbreds seen at P2, P14 and thereafter was complemented by attenuated developmental cell death. The differences in programmed cell death were confirmed by reduced TUNEL labelling, AIF and caspase-3 expression. GDNF expression aligned with the cell death pattern at P2 and P14 in both nigra and striatum. Earlier maturity of nigra and its neurons appear to be better features that reflect as MPTP-resistance at adulthood. Thus variable MPTP-vulnerability in mice and also differential susceptibility to PD in humans may arise early during nigral development.

show abstract

Aging mildly affects dendritic arborisation and synaptic protein expression in human substantia nigra pars compacta

Cited by 9 publications

References 36 publications

Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson’s Disease

Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson’s Disease

Differences in Neuronal Numbers, Morphology, and Developmental Apoptosis in Mice Nigra Provide Experimental Evidence of Ontogenic Origin of Vulnerability to Parkinson’s Disease

Differences in neuronal numbers, morphology and developmental apoptosis in mice nigra provide experimental evidence of ontogenic origin of vulnerability to Parkinson’s disease

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