Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

Vaswani, Ankita Ravi; Weykopf, Beatrice; Hagemann, Cathleen; Fried, Hans-Ulrich; Brüstle, Oliver; Blaess, Sandra

doi:10.7554/elife.41623

Cited by 20 publications

(25 citation statements)

References 73 publications

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“…A similar observation was published by Salinger et al [ 42 ] who found behavioural deficits in homozygous reelin mice but not HRM. We chose not to use full knockouts because it is known that these animals display marked disorganization of cortical and hippocampal layering [ 43 , 44 ] as well as malformation of midbrain dopamine cell groups [ 45 ]. Moreover, the reduction of reelin levels in post-mortem schizophrenia brains was reported to be approximately 50% [ 3 ], comparable to the levels in HRM [ 6 ], rather than complete depletion.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia

2020

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Reelin has been implicated in the development of schizophrenia but the mechanisms involved in this interaction remain unclear. Chronic methamphetamine (Meth) use may cause dopaminergic sensitisation and psychosis and has been proposed to affect brain dopamine systems similarly to changes seen in schizophrenia. We compared the long-term effect of chronic Meth treatment between heterozygous reelin mice (HRM) and wildtype controls (WT) with the aim of better understanding the role of reelin in schizophrenia. Meth pretreatment induced sensitisation to the effect of an acute Meth challenge on locomotor activity, but it had no effect on baseline PPI or sociability and social preference. In all behavioural models, HRM did not significantly differ from WT at baseline, except spontaneous exploratory locomotor activity which was higher in HRM than WT, and sociability which was enhanced in HRM. Locomotor hyperactivity sensitisation was not significantly different between HRM and WT. Chronic Meth treatment reduced spontaneous locomotor activity to the level of WT. No deficits in PPI or social behaviour were induced by chronic Meth pretreatment in either strain. In conclusion, these data do not support a role of reelin in schizophrenia, at least not in HRM and in the methamphetamine sensitisation model.

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Section: Discussionmentioning

confidence: 99%

The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia

2020

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“…In the midbrain, YFPexpression starts in laterally located TH-positive DaNs at E13.5 and spreads to medial DaN populations by E15.5 ( Fig. 1) [37]. In the OB, we could not detect any YFPexpression in TH-positive DaNs at E15.5 ( Fig.…”

Section: Time Course Of Tfam Loss In Different Dan Populationsmentioning

confidence: 81%

The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection

et al. 2020

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Understanding non-motor symptoms of Parkinson's disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson's disease patients. Mitochondrial dysfunction is a key feature in Parkinson's disease and importantly contributes to the selective loss of dopaminergic neurons the substantia nigra pars compacta. The olfactory bulb, the first olfactory processing station, also contains dopaminergic neurons, which modulate odor information and thereby enable odor detection as well as odor discrimination. MitoPark mice are a genetic model for Parkinson's disease with severe mitochondrial dysfunction, reproducing the differential vulnerability of dopaminergic neurons in the midbrain. These animals were used to investigate the impact of mitochondrial dysfunction on olfactory-related behavior and olfactory bulb dopaminergic neuron survival. Odor detection was severely impaired in MitoPark mice. Interestingly, only the small anaxonic dopaminergic subpopulation, which is continuously replenished by neurogenesis, was moderately reduced in number, much less compared with dopaminergic neurons in the midbrain. As a potential compensatory response, an enhanced mobilization of progenitor cells was found in the subventricular zone. These results reveal a high robustness of dopaminergic neurons located in the olfactory bulb towards mitochondrial impairment, in striking contrast to their midbrain counterparts.

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“…The findings of the present study may reflect disruption of the polarity and/or destabilization of actin cytoskeleton in the cell body due to RELN-del. Moreover, a recent study using mice reported that reelin stabilizes the leading process morphology in dopaminergic neurons during their migration 13 . Thus, reelin may control neuronal migration via regulation of whole neuronal morphology, including the cell body and associated processes, even in vitro, such as in human iPSC-derived dopaminergic neurons.…”

Section: Discussionmentioning

confidence: 99%

Cell body shape and directional movement stability in human-induced pluripotent stem cell-derived dopaminergic neurons

Arioka¹,

Shishido²,

Kushima³

et al. 2020

Sci Rep

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Neuronal migration is necessary in the process of the formation of brain architecture. Recently, we demonstrated that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration in vitro. However, it remains unclear how the cell shape is involved in their migration. In this study, we performed live imaging analyses using human iPSC-derived dopaminergic neurons. Our automated method, which can automatically identify the cell body shape and the cell position at specific time points, revealed that healthy iPSC-derived dopaminergic neurons migrate according to their shape. This migration behavior was out of accord in neurons derived from iPSCs carrying an RELN deletion. Our findings provide a novel theory that cell body orientation is related to the stability of movement direction for human dopaminergic neurons, under the regulation of RELN.

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Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

Cited by 20 publications

References 73 publications

The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia

The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia

The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection

Cell body shape and directional movement stability in human-induced pluripotent stem cell-derived dopaminergic neurons

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