Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from inflammatory degeneration via BDNF‐mediated signaling

Katsuki, Hiroshi; Kurimoto, Emi; Takemori, Sachiko; Kurauchi, Yuki; Hisatsune, Akinori; Isohama, Yoichiro; Izumi, Yasukatsu; Kume, Toshiaki; Shudo, Koichi; Akaike, Akinori

doi:10.1111/j.1471-4159.2009.06171.x

Cited by 81 publications

(68 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this, derepression of Nurr1 target genes (Jacobs et al, 2009a) upon release of SMRT-HDAC repressive complexes, as described above, might indicate why Bdnf exposure is beneficial for mdDA neuron development and function (Sortwell, 2003). Moreover, it has been shown that Bdnf signaling, RA signaling and NO signaling intersect in the protection of mdDA neurons (Katsuki et al, 2009;Kurauchi et al, 2011). It is therefore possible that these converging signaling events act via common mechanisms that involve changing the epigenetic state of Nurr1 target genes through release of HDAC-mediated repression.…”

Section: Reviewmentioning

confidence: 74%

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

et al. 2013

View full text Add to dashboard Cite

SummaryMesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesodiencephalon and are involved in psychiatric disorders and severely affected in neurodegenerative diseases such as Parkinson's disease. mdDA neuronal development has received much attention in the last 15 years and many transcription factors involved in mdDA specification have been discovered. More recently however, the impact of epigenetic regulation has come into focus, and it's emerging that the processes of histone modification and DNA methylation form the basis of genetic switches that operate during mdDA development. Here, we review the epigenetic control of mdDA development, maturation and maintenance. As we highlight, epigenetic mechanisms play a pivotal role in all of these processes and the knowledge gathered from studying epigenetics in these contexts may aid our understanding of mdDA-related pathologies. Key words: Brain, Development, Dopamine, Epigenetics, Gene regulation, Midbrain IntroductionIf you turn this page, both the decision you make and the action that you carry out are significantly influenced by the amount of dopamine (DA; see Glossary, Box 1) released from dopaminergic neurons within your brain. Mesodiencephalic dopaminergic (mdDA) neurons located in the substantia nigra pars compacta (SNc; see Glossary, Box 1), in particular, are essential for motor functions whereas mdDA neurons of the ventral tegmental area (VTA; see Glossary, Box 1) and the retrorubal field (RRF; see Glossary, Box 1) are involved in the regulation of emotions and reward . Notably, severe loss of SNc mdDA neurons is a pathological hallmark of Parkinson's disease (PD) (Sulzer, 2007). By contrast, mdDA neurons in the VTA and RRF, which remain intact in PD, are part of the mesocorticolimbic system (see Glossary, Box 1), in which defective DA neurotransmission has been implicated in the development of drug addiction, depression and schizophrenia (Nestler, 2000). Given their involvement in neurodegenerative diseases and psychiatric disorders, mdDA neurons have been studied intensively in recent years.In the last two decades, a variety of molecular approaches have revealed factors that are specific for mdDA neuronal subsets or that guide their spatial organization ; recently, a pathway that molecularly distinguishes SNc DA neurons from those located in the VTA was identified (Jacobs et al., 2011). In addition to molecular profiling of DA neurons, however, a second level of complexity has been added by the rapidly emerging field of epigenetics, which has provided new insights into the origin and maintenance of distinctive gene expression patterns in mdDA neurons. Current definitions of epigenetics often emphasize the heritability of changes in gene expression throughout cell divisions that are not due to alterations in DNA sequence. However, perhaps a more appropriate definition of epigenetics, especially when applying this term to mature neurons that cannot divide, is postulated by Adrian Bird: 'The structural adaptation of chromosomal regio...

show abstract

Section: Reviewmentioning

confidence: 74%

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Because BDNF treatment augmented the survival of mdDA neurons in primary VM cultures prepared from E11.5 Pitx3 GFP/GFP -null mutant embryos, we suggest that the failure to induce BDNF expression in rostrolateral and medial (SNc) mdDA precursors during development contributes to the preferential degeneration of these neurons in the Pitx3 GFP/GFP mice. Interestingly, retinoid signaling via retinoic acid receptors was recently shown to induce BDNF transcription and to prevent the inflammatory degeneration of mdDA neurons in vitro and in vivo (Katsuki et al, 2009). While our data strongly suggest a direct activation of the BDNF gene by Pitx3, we cannot exclude that Pitx3 might indirectly maintain BDNF expression through the induction of Aldh1a1 and subsequent local production of RA in an mdDA neuronal subset.…”

Section: Discussionmentioning

confidence: 99%

Pitx3 Is a Critical Mediator of GDNF-Induced BDNF Expression in Nigrostriatal Dopaminergic Neurons

Peng¹,

Aron²,

Klein³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

Ϫ/Ϫ mdDA neurons. Most importantly, only BDNF but not GDNF protects mdDA neurons against 6-hydroxydopamine-induced cell death in the absence of Pitx3. As the feedforward regulation of GDNF, Pitx3, and BDNF expression also persists in the adult rodent brain, our data suggest that the disruption of the regulatory interaction between these three factors contributes to the loss of mdDA neurons in Pitx3 Ϫ/Ϫ mutant mice and perhaps also in human PD.

show abstract

“…This assumption was based on the fact that RAR stimulation suppressed inflammatory responses of microglia (85). In addition, we recently found that RAR stimulation by the specific agonist Am80 (tamibarotene) increased expression of brain-derived neurotrophic factor in brain tissues and protected midbrain dopaminergic neurons from inflammatory degeneration (86,87). Therefore, both the anti-inflammatory action and neurotrophic action of the RAR agonist might exert beneficial influences on the integrity of brain tissue after ICH (Fig.…”

Section: Nuclear Receptor Ligandsmentioning

confidence: 99%

Exploring Neuroprotective Drug Therapies for Intracerebral Hemorrhage

Katsuki

2010

J Pharmacol Sci

Self Cite

View full text Add to dashboard Cite

Abstract. Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high mortality and poor prognosis, for which virtually no effective drug therapies are available at present. Experimental animal models, based on intrastriatal injection of collagenase or autologous blood, have enabled great advances in elucidation of cellular/molecular events contributing to brain pathogenesis associated with ICH. Many lines of evidence indicate that blood constituents, including hemoglobin-derived products as well as proteases such as thrombin, play important roles in the pathogenic events. Inflammatory reactions involving neutrophils, activated microglia, and production of proinflammatory cytokines also constitute a critical aspect of pathology leading to neurodegeneration and tissue damage. Efforts are continuing to find drugs that potentially alleviate pathologi cal and neurological outcomes of ICH. Various drugs that possess antioxidative, antiinflammatory or neurotrophic/neuroprotective properties have been demonstrated to produce therapeutic effects on ICH animal models. Drugs already in clinical use such as minocycline, statins, and several nuclear receptor ligands are among the list of effective drugs, but whether they also show therapeutic efficacy in human ICH patients remains unproven. Here, current knowledge of ICH pathogenesis and problems arising with respect to exploration of new drug candidates are discussed.

show abstract

Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from inflammatory degeneration via BDNF‐mediated signaling

Cited by 81 publications

References 39 publications

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Pitx3 Is a Critical Mediator of GDNF-Induced BDNF Expression in Nigrostriatal Dopaminergic Neurons

Exploring Neuroprotective Drug Therapies for Intracerebral Hemorrhage

Contact Info

Product

Resources

About