Unilateral lesion of the subthalamic nucleus transiently provokes bilateral subacute glial cell proliferation in the adult rat substantia nigra

Steiner, Barbara; Kupsch, Andreas; Siebert, Eberhard; Hosmann, Kai; Klempin, Friederike; Morgenstern, Rudolf; Winter, Christine

doi:10.1016/j.neulet.2007.10.045

Cited by 11 publications

(7 citation statements)

References 26 publications

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“…Based on the observations described here we think that these Dcx + cells in the SN have previously been missed, because the expression levels of Dcx in the SN are much lower than for example in the rostral migratory stream or the DG. Additionally, in some studies Dcx is co‐immunostained with BrdU (Van Kampen & Eckman, ; Steiner et al ., ). BrdU immunostaining, however, requires DNA denaturation to single strands, a step that alters many antigens and thereby often interferes with antibody binding and the detection of low expression level proteins (Cavanagh et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Interestingly, in our study we found a high percentage of Dcx + cells among the EdU + cells in the SN. This finding is particularly interesting in light of previous reports describing the absence of Dcx + cells in the SN (Frielingsdorf et al ., ; Mohapel et al ., ; Van Kampen & Eckman, ; Steiner et al ., , ; Klaissle et al ., ). Another study describes the identification of Dcx + cells in the SN only after nigral DA degeneration plus additional FGF‐2 injections, but not after DA degeneration alone (Peng et al ., ).…”

Section: Discussionmentioning

confidence: 99%

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The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation

Worlitzer

Viel²,

Jacobs³

et al. 2013

Eur J of Neuroscience

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Parkinson's disease is characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). However, whether regenerative endogenous neurogenesis is taking place in the mammalian SN of parkinsonian and non-parkinsonian brains remains of debate. Here, we tested whether proliferating cells in the SN and their neurogenic potential would be affected by anti-inflammatory treatment under physiological conditions and in the 6-hydroxy-dopamine (6-OHDA) Parkinson's disease mouse model. We report that the majority of newly generated nigral cells are positive for Doublecortin (Dcx), which is an often used marker for neural progenitor cells. Yet, Dcx expression levels in these cells were much lower than in neural progenitor cells of the subventricular zone and the dentate gyrus neural progenitor cells. Furthermore, these newly generated nigral cells are negative for neuronal lineage markers such as TuJ1 and NeuN. Therefore, their neuronal commitment is questionable. Instead, we found evidence for oligodendrogenesis and astrogliosis in the SN. Finally, neither short-term nor long-term inhibition of neuroinflammation by Minocycline- or 6-OHDA-induced lesion affected the numbers of newly generated cells in our disease paradigm. Our findings of adult generated Dcx(+) cells in the SN add important data for understanding the cellular composition and consequently the regenerative capacity of the SN.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation

Worlitzer

Viel²,

Jacobs³

et al. 2013

Eur J of Neuroscience

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“…Interestingly, Worlitzer et al () found a high percentage of DCX+ cells among the EdU+ cells in the SN. However, previous reports failed to demonstrate the presence of DCX+ cells in the SN (Frielingsdorf et al, ; Mohapel et al, ; Van Kampen and Eckman, ; Steiner et al, ; Klaissle et al, ). The explanation for these conflicting results may be due to the coimmunostaining of DCX with BrdU that often interferes with antibody binding of proteins with a low expression level.…”

Section: Use Of Exogenous Factors In Inducing Daergic Neurogenesismentioning

confidence: 93%

“…Other interesting findings involve the presence of low levels of oligodendrogenesis and astrogliogenesis in the SN after 6-OHDA lesion. However, the findings seem to be strongly dependent on the model and the timepoint of investigation (Kay and Blum, 2000;Lie et al, 2002;Yoshimi et al, 2005;Steiner et al, 2008;Klaissle et al, 2012). Nevertheless, increasing evidence suggests oligodendrogenesis as an interesting new potential therapeutic target in PD (Worlitzer et al, 2012).…”

Section: Neurogenesis In the Sn: Healthy Brain And Pd Modelsmentioning

confidence: 99%

Harnessing neurogenesis for the possible treatment of Parkinson's disease

Lamm

Ganz

Melamed

et al. 2014

J of Comparative Neurology

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The discovery of neurogenesis in the adult brain has created new possibilities for therapeutics in neurodegenerative diseases. Neural precursor cells, which have been found in various parts of the brain, e.g., the subventricular zone (SVZ) and substantia nigra (SN), have promising potential to replace the extensive loss of neurons occurring in neurodegenerative disorders. In Parkinson's disease (PD) the degeneration of nigral dopaminergic neurons and consequently the nigrostriatal pathway, which has been found to innervate proximally to the SVZ, causes motor and cognitive impairments. There is strong evidence that neurogenesis is impaired in PD, which has been related to the nonmotor symptoms of the disease. Recent evidence supports that this impairment in neurogenesis is partially caused by the lack of dopamine in one of the adult neurogenic niches, the SVZ. Thus, restoring the dopaminergic pathway in PD patients may have implications not only for motor function improvement, but for other cognitive and autonomic symptoms. Currently, there are no effective treatments that can stop or reverse the neurodegeneration process in the brain. Here we review the neurogenic process and observed alterations found in PD animal models and postmortem brains of PD patients. Finally, we review several attempts to stimulate the neurogenic process for nigral and/or striatal dopaminergic restoration by transgenic expression, exercise, or cell therapy.

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“…Peng et al reported that fibroblast growth factor 2 increased the number of BrdU and doublecortin double positive cells in SN of MPTP-lesioned mice (Peng et al, 2008). Others reported that either physical activity or Unilateral lesion of the subthalamic nucleus increased the oligodendrogenesis and astrogliogenesis in the SN after 6-OHDA lesion (Steiner et al, 2008; Klaissle et al, 2012). Recently, it was also reported that the majority of newly generated cells in the adult mouse SN express low levels of doublecortin (Worlitzer et al, 2013).…”

Section: Apα Improves Balance and Coordination And Increases The Numbmentioning

confidence: 99%

Allopregnanolone and neurogenesis in the nigrostriatal tract

Wang

2014

Front. Cell. Neurosci.

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Reinstalling the neurobiological circuits to effectively change the debilitating course of neurodegenerative diseases is of utmost importance. This reinstallation requires generation of new cells which are able to differentiate into specific types of neurons and modification of the local environment suitable for integration of these new neurons into the neuronal circuits. Allopregnanolone (APα) seems to be involved in both of these processes, and therefore, is a potential neurotrophic agent. Loss of dopamine neurons in the substantia nigra (SN) is one of the main pathological features of Parkinson’s and also in, at least, a subset of Alzheimer’s patients. Therefore, reinstallation of the dopamine neurons in nigrostriatal tract is of unique importance for these neurodegenerative diseases. However, for the neurogenic status and the roles of allopregnanolone in the nigrostriatal tract, the evidence is accumulating and debating. This review summarizes recent studies regarding the neurogenic status in the nigrostriatal tract. Furthermore, special attention is placed on evidence suggesting that reductions in allopregnenalone levels are one of the major pathological features in PD and AD. This evidence has also been confirmed in brains of mice that were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or those bearing neurodegenerative mutations. Lastly, we highlight studies showing that allopregnanalone can augment the number of total cells and dopaminergic neurons via peripheral exogenous administration.

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Unilateral lesion of the subthalamic nucleus transiently provokes bilateral subacute glial cell proliferation in the adult rat substantia nigra

Cited by 11 publications

References 26 publications

The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation

The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6‐OHDA‐induced nigral lesion or Minocycline‐mediated inhibition of neuroinflammation

Harnessing neurogenesis for the possible treatment of Parkinson's disease

Allopregnanolone and neurogenesis in the nigrostriatal tract

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