Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb

Winner, Beate; Geyer, Martin; Couillard‐Després, Sébastien; Aigner, Robert; Bogdahn, Ulrich; Aigner, Ludwig; Kuhn, H. Georg; Winkler, Jürgen

doi:10.1016/j.expneurol.2005.08.028

Cited by 146 publications

(122 citation statements)

References 56 publications

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“…The primary target of the dopaminergic afferents in the SEZ are TAPs, which express the D2-type dopamine receptors and proliferate in response to dopamine stimulation [115,116]. Consistently, experimental ablation of dopaminergic afferents results in reduced SEZ proliferation which is mainly attributable to TAPs [115,117,118]. Interestingly, recent evidence suggests that the dopamine induced increase in cell proliferation and neurogenesis in the adult SEZ is dependent on CNTF [119].…”

Section: Signaling Within the Ansc Nichementioning

confidence: 78%

Stem cells of the adult mammalian brain and their niche

Basak

Taylor

2008

Cell. Mol. Life Sci.

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Abstract. The mammalian brain is a paradox of evolution. Although the advance in complexity of the human brain has exceeded the development of other organs, it has practically lost the ability to regenerate, and damage is repaired mainly by functional plasticity. This disparity is, however, not due to the lack of progenitor cells in the adult mammalian brain, but to their diminished or repressed capacity to replace neurons in most brain regions. Here, we discuss the current literature describing the processes of neurogenesis in the adult mammalian brain, and the recent advances in adult neural stem cells (aNSCs) with a focus on their identity, cell cycle and niche signals. Understanding these processes may hopefully lead to therapies in the future to reinstate self-repair of the brain from endogenous progenitors.Keywords. Neural stem cells, neurogenesis, stem cell niche, adult brain, subventricular zone. The discovery of neurogenesis in the adult brainNSCs are the foundations of the brain during development, and despite poor regenerative capacity, they persist in the mammalian brain throughout postnatal development and into adulthood and continue to generate neurons. aNSCs self-renew and retain multipotency in almost all mammalian species analyzed, including humans. NSCs reside in specialized germinal layers where multiple cell-types interact with them and contribute to generate niches that control their fate choices and permit neurogenesis. Genetic and functional analyses have revealed roles for several genes and signaling pathways in controlling adult neurogenesis. However, the identities of the stem cells in the brain remain elusive, which presents an elementary problem for the interpretation of these results. In attempts to identify aNSCs, several groups have defined populations that contain cells with stem cell features, although unambiguous markers are still missing. Given their potential as putative tools for cell-based therapies, elucidating the molecular pathways that identify aNSCs and govern their cell fate is essential. Neurons in most regions of the adult mammalian brain are generated from NSCs and restricted progenitors during embryonic development before a switch to gliogenesis in peri-and postnatal development [1]. As early as the 1960s and 70s, newly generated neurons were identified by nucleotide analogue incorporation assays in adult rodents [2, 3]. These results, however, met with skepticism due to the poor regenerative capacity of the mammalian brain. Detailed studies went on to show extensive neurogenesis in the vocal control center in the brains of adult canaries, which correlates with seasonal song learning [4,5]. After a brief re-visitation to the topic in the mid-1980s, it was the use of retroviral lineage tracing assays that identified newborn neurons in the adult mammalian brain. These findings were quickly followed by the identification of zones with neurogenic capacity in

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Section: Signaling Within the Ansc Nichementioning

confidence: 78%

Stem cells of the adult mammalian brain and their niche

Basak

Taylor

2008

Cell. Mol. Life Sci.

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“…As would be predicted, loss of the dopaminergic nigrostriatal tract innervating the SVZ using the neurotoxins MPTP and 6-OHDA, leads to a reduction in neural precursor cell proliferation [14][15][16]24 with the degree of reduction being correlated to the extent of dopaminergic denervation. 15 In our previous experiments, we used Levodopa, a dopamine precursor, to restore the dopamine-depleted animals to normal and showed that proliferation in the SVZ returned to baseline levels.…”

Section: Neurogenesismentioning

confidence: 94%

Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain

O’Keeffe¹,

Barker²,

Caldwell³

2009

Cell Cycle

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“…This further indicates that tg ␣-syn directly induced progressive motor decline and, additionally, that disease progression depends on continuous presence of transgene expression. However, the nonreversibility of symptoms in treated CaM_␣-syn mice suggested that neurodegeneration and nigral axon pathology was not ameliorated by a compensatory effect as increased neurogenesis, which might be a frequent response to injury in rodents (Arvidsson et al, 2002;Nakatomi et al, 2002;Zhao et al, 2003;Winner et al, 2006) and human brain (Huisman et al, 2004). Analysis of neurogenesis of 6-month-old CaM_␣-syn mice consistently revealed a negative impact on progenitor cells in the granular cell layer of the dentate gyrus.…”

Section: Discussionmentioning

confidence: 99%

Neurodegeneration and Motor Dysfunction in a Conditional Model of Parkinson's Disease

Nuber¹,

Petrasch‐Parwez²,

Winner³

et al. 2008

J. Neurosci.

165

134

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␣-Synuclein (␣-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease. These disorders are characterized by various neurological and psychiatric symptoms based on progressive neuropathological alterations. Whether the neurodegenerative process might be halted or even reversed is presently unknown. Therefore, conditional mouse models are powerful tools to analyze the relationship between transgene expression and progression of the disease. To explore whether ␣-syn solely originates and further incites these alterations, we generated conditional mouse models by using the tet-regulatable system. Mice expressing high levels of human wild-type ␣-syn in midbrain and forebrain regions developed nigral and hippocampal neuropathology, including reduced neurogenesis and neurodegeneration in absence of fibrillary inclusions, leading to cognitive impairment and progressive motor decline. Turning off transgene expression in symptomatic mice halted progression but did not reverse the symptoms. Thus, our data suggest that approaches targeting ␣-syn-induced pathological pathways might be of benefit rather in early disease stages. Furthermore, ␣-syn-associated cytotoxicity is independent of filamentous inclusion body formation in our conditional mouse model.

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Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb

Cited by 146 publications

References 56 publications

Stem cells of the adult mammalian brain and their niche

Stem cells of the adult mammalian brain and their niche

Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain

Neurodegeneration and Motor Dysfunction in a Conditional Model of Parkinson's Disease

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