Dopamine and adult neurogenesis

Borta, Andreas; Höglinger, Günter U.

doi:10.1111/j.1471-4159.2006.04241.x

Cited by 170 publications

(154 citation statements)

References 64 publications

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“…However, our FluoroGold tracing experiments unequivocally demonstrate that the cellcycle-like processes observed in vivo occurred in neurons that were already present before their intoxication. Thus, in agreement with other studies (15,23,24), we found no evidence for spontaneous or lesion-induced, transient or persistent, generation of new TH ϩ neurons in the adult SNc.…”

Section: Discussionsupporting

confidence: 81%

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The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease

Höglinger

Breunig

Depboylu

et al. 2007

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

248

223

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The mechanisms leading to degeneration of dopaminergic neurons (DNs) in the substantia nigra of patients with Parkinson's disease (PD) are not completely understood. Here, we show, in the postmortem human tissue, that these neurons aberrantly express mitosis-associated proteins, including the E2F-1 transcription factor, and appear to duplicate their nuclear DNA. We further demonstrate that the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injected into mice and application of its active metabolite 1-methyl-4-phenylpyridinium to mesencephalic cultures activate the retinoblastoma-E2F pathway in postmitotic DNs. We also find that cell death rather than mitotic division followed the toxin-induced replication of DNA, as determined by BrdU incorporation in DNs. In addition, blocking E2F-1 transcription protected cultured DNs against 1-methyl-4-phenylpyridinium toxicity. Finally, E2F-1-deficient mice were significantly more resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic cell death than their wild-type littermates. Altogether, BrdU incorporation in mature neurons and lack of evidence for newborn neurons argue against neuronal turnover in normal conditions or during pathological states in the substantia nigra. Instead, our results demonstrate that mitosis-like signals are activated in mature DNs in patients with PD and mediate neuronal death in experimental models of the disease. Inhibition of mitosis-like signals may therefore provide strategies for neuroprotection in PD.adult neurogenesis ͉ neurodegeneration ͉ retinoblastoma ͉ apoptosis ͉ dopamine

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Section: Discussionsupporting

confidence: 81%

“…Together, the available data suggest that cell cycle-associated mechanisms are linked to the process of neurodegeneration in PD. However, there have also been reports suggesting constitutive and lesioninduced neurogenesis in the adult SNc (15). Therefore, the observed cell-cycle events could be related to de novo generation of DNs as well.…”

mentioning

confidence: 97%

The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease

Höglinger

Breunig

Depboylu

et al. 2007

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

248

223

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“…This adds to a list of studies that are revealing unexpected effects of neurotransmitters on neural stem/progenitor cell function. Apart from the work on the glutamatergic NMDA receptor subtype (Cameron et al, 1995;Gould and Cameron, 1997;Nacher and Mcewen, 2006), the dopaminergic impact on stem/progenitor cell proliferation during brain development and in adult neurogenesis has also been examined (Borta and Hoglinger, 2007;Hoglinger et al, 2004;Kippin et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Benninghoff¹,

Gritti²,

Rizzi³

et al. 2009

Neuropsychopharmacol

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Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.

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“…We found that cell proliferation in the hippocampal dentate gyrus was significantly increased following hypoxic ischemia, indicating that hypoxic ischemia induces cell proliferation in the hippocampal dentate gyrus. Hypoxic ischemia-induced enhancement of cell proliferation in the dentate gyrus has been suggested as a compensatory adaptive response to excessive apoptosis following ischemic brain injury (Liu et al 1998;Ko et al 2009) through alteration of dopaminergic inputs from the SN neurons (Borta and Höglinger 2007).…”

Section: Discussionmentioning

confidence: 99%

Hypothermia alleviates hypoxic ischemia-induced dopamine dysfunction and memory impairment in rats

Cho

Kim

et al. 2011

Animal Cells and Systems

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(2011) Hypothermia alleviates hypoxic ischemia-induced dopamine dysfunction and memory impairment in rats, Animal Cells and Systems, 15:4, 279-286, DOI: 10.1080/19768354.2011.607514 To link to this article: https://doi.org/10. 1080/19768354.2011 Hypoxic ischemia injury is a common cause of functional brain damage, resulting from a decrease in cerebral blood flow and oxygen supply to the brain. The main problems associated with hypoxic ischemia to the brain are memory impairment and dopamine dysfunction. Hypothermia has been suggested to ameliorate the neurological impairment induced by various brain insults. In this study, we investigated the effects of hypothermia on memory function and dopamine synthesis following hypoxic ischemia to the brain in rats. For this purpose, a step-down avoidance task, a radial eight-arm maze task, and immunohistochemistry for tyrosine hydroxylase (TH) and 5-bromo-2?-deoxyuridine (BrdU) were performed. The present results indicated that the hypoxic ischemia-induced disturbance of the animal's performances and spatial working memory was associated with a decrement in TH expression in the substantia nigra and striatum, and an increase in cell proliferation in the hippocampal dentate gyrus. Hypothermia treatment improved the animals' performance and spatial working memory by suppressing the decrement in TH expression in the substantia nigra and striatum and the increase in cell proliferation in the dentate gyrus. We suggest that hypothermia can be an efficient therapeutic modality to facilitate recovery following hypoxic ischemia injury to the brain, presumably by modulating the dopaminergic cell loss.

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Dopamine and adult neurogenesis

Cited by 170 publications

References 64 publications

The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease

The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Hypothermia alleviates hypoxic ischemia-induced dopamine dysfunction and memory impairment in rats

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