Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model

Parish, Clare L.; Beljajeva, Anna; Arenas, Ernest; Simon, András

doi:10.1242/dev.002329

Cited by 103 publications

(93 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 10 min, the brain was rinsed thoroughly and transferred to a chamber perfused with oxygenated Ringer's solution for 3-4 h at room temperature to allow retrograde transport of the tracers. The injection sites were chosen based on previous studies on the MLR (5, 7, 59), middle reticular nucleus (mRN) (7,60,61), and striatum (15,62) and verified by histology. The preparations were then transferred to a fixative solution according to the immunofluorescence procedure to follow.…”

Section: Methodsmentioning

confidence: 99%

“…No labeling occurred when the primary antibodies were left out of the procedures. TH immunofluorescence was used to visualize DA neurons, based on studies in salamanders (28,62). The presence of DA was examined with DA immunofluorescence, in which case TBMBS was used as buffer with 0.5% Triton X-100 and 5% (vol/vol) normal goat serum.…”

Section: Methodsmentioning

confidence: 99%

“…The stimulation intensities ranged from 1 to 15 μA. The stimulation site was chosen based on a previous study (62) and gathered data from the present study.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A descending dopamine pathway conserved from basal vertebrates to mammals

Ryczko

Cone

Alpert

et al. 2016

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

104

View full text Add to dashboard Cite

Dopamine neurons are classically known to modulate locomotion indirectly through ascending projections to the basal ganglia that project down to brainstem locomotor networks. Their loss in Parkinson's disease is devastating. In lampreys, we recently showed that brainstem networks also receive direct descending dopaminergic inputs that potentiate locomotor output. Here, we provide evidence that this descending dopaminergic pathway is conserved to higher vertebrates, including mammals. In salamanders, dopamine neurons projecting to the striatum or brainstem locomotor networks were partly intermingled. Stimulation of the dopaminergic region evoked dopamine release in brainstem locomotor networks and concurrent reticulospinal activity. In rats, some dopamine neurons projecting to the striatum also innervated the pedunculopontine nucleus, a known locomotor center, and stimulation of the dopaminergic region evoked pedunculopontine dopamine release in vivo. Finally, we found dopaminergic fibers in the human pedunculopontine nucleus. The conservation of a descending dopaminergic pathway across vertebrates warrants re-evaluating dopamine's role in locomotion.D opaminergic neurons represent a vital neuromodulatory component essential for vertebrate motor control, and their loss in neurodegenerative disease is devastating. The meso-diencephalic dopamine (DA) neurons are known to provide ascending projections to the basal ganglia, which, in turn, provide input to cortical structure in mammals but also project caudally to the mesencephalic locomotor region (MLR), a highly conserved structure that controls locomotion in all vertebrates investigated to date (1-7; for review, see ref. 8). A growing body of evidence supports the view that basal ganglia connectivity is highly conserved among vertebrates, from lampreys to mammals (9-11; for review, see ref. 12), with some interspecies differences recently highlighted (13). As such, the homology between DA cell populations remains to be resolved in vertebrates. As a general rule, DA neurons from the meso-diencephalon send projections to the striatum in all vertebrates. In lampreys and teleosts, those neurons are located only in the diencephalon (posterior tuberculum), but in tetrapods and cartilaginous fishes (14) they are located in both the diencephalon and the mesencephalon. An increasing number of authors seem to agree with the hypothesis that at least some of the mesodiencephalic DA neurons located in the diencephalon are homologous in all vertebrates, and thus, homologous to at least a portion of the mammalian substantia nigra pars compacta (SNc)/ ventral tegmental area (VTA) (13, 15-19; for review, see ref. 20). Alternatively, it was suggested that the posterior tuberculum DA neurons projecting to the striatum in zebrafish are homologs of the mammalian DA neurons of the A11 group (21). This will be discussed below in light of the results of the present study.In lampreys, only a few meso-diencephalic DA neurons send ascending projections to the striatum (9, 22); the majority ...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A descending dopamine pathway conserved from basal vertebrates to mammals

Ryczko

Cone

Alpert

et al. 2016

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

104

View full text Add to dashboard Cite

show abstract

“…developmental biology | immunology | limb development | wound healing S alamanders have the remarkable ability to regenerate complex structures such as limbs, tails, retina, and spinal cord, along with some sections of the heart and brain, during any stage of their life cycle (1)(2)(3)(4)(5)(6)(7). Salamanders are also able to perform scar-free repair of deep tissue wounds after injury (8).…”

mentioning

confidence: 99%

Macrophages are required for adult salamander limb regeneration

Godwin

Pinto

Rosenthal

2013

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

705

765

View full text Add to dashboard Cite

The failure to replace damaged body parts in adult mammals results from a muted growth response and fibrotic scarring. Although infiltrating immune cells play a major role in determining the variable outcome of mammalian wound repair, little is known about the modulation of immune cell signaling in efficiently regenerating species such as the salamander, which can regrow complete body structures as adults. Here we present a comprehensive analysis of immune signaling during limb regeneration in axolotl, an aquatic salamander, and reveal a temporally defined requirement for macrophage infiltration in the regenerative process. Although many features of mammalian cytokine/chemokine signaling are retained in the axolotl, they are more dynamically deployed, with simultaneous induction of inflammatory and anti-inflammatory markers within the first 24 h after limb amputation. Systemic macrophage depletion during this period resulted in wound closure but permanent failure of limb regeneration, associated with extensive fibrosis and disregulation of extracellular matrix component gene expression. Full limb regenerative capacity of failed stumps was restored by reamputation once endogenous macrophage populations had been replenished. Promotion of a regeneration-permissive environment by identification of macrophage-derived therapeutic molecules may therefore aid in the regeneration of damaged body parts in adult mammals.

show abstract

“…To clarify this issue, it is required to trace the lineage of newly produced DA neurons in the adult brain with local virus infection or genetic manipulations. While DA neurogenesis is unclear in rodents, newts appear to maintain complete potency to regenerate DA neuron in association with stem cell proliferation and genesis of new DA neurons in the midbrain (Parish et al, 2007). Thus, it appears that the ability to produce new DA neurons distinguished or markedly reduced during evolution, and thus it is important to evaluate the extent of new cell production in the human SN for therapeutic application.…”

Section: Discussionmentioning

confidence: 99%

Effects of 6-hydroxydopamine on the Adult Neurogenesis of Dopaminergic Neurons in the Mouse Midbrain

Kim

Sun

2009

Exp Neurobiol

View full text Add to dashboard Cite

Recently, restricted progenitor cells have been identified in the substantia nigra (SN) of the rat and mouse, raising a hope that resident stem/progenitor cells may be useful for the therapy of Parkinson's disease. However, it is controversial whether dopamine (DA) neurons can be spontaneously or injury-dependently generated from the endogenous stem cells in the adult brain. Here, we explored the neurogenesis in C57Bl/6 adult mice under the normal and neurotoxin-injured conditions. To monitor adult neurogenesis, we injected 5-bromodeoxyuridine (BrdU) 2 weeks after striatal injection of neurotoxin 6-hydroxydopamine (6-OHDA), and sacrificed the animals 6 weeks after 6-OHDA injection. Whereas the number of BrdU-labeled cells was slightly increased in ipsilateral side than contralateral side of the midbrain, none of BrdUlabeled cells, however, exhibited neuronal markers, NeuN or DCX. Instead, BrdUlabeled cells expressed glial markers such as GFAP (astrocyte), Olig2 (oligodendrocyte) and Iba-1 (microglia). Especially, larger portion of BrdU-labeled cells in the ipsilateral side exhibited microglial marker, indicating that increased cell production in response to the 6-OHDA injection is not related to the adult neurogenesis.

show abstract

Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model

Cited by 103 publications

References 33 publications

A descending dopamine pathway conserved from basal vertebrates to mammals

A descending dopamine pathway conserved from basal vertebrates to mammals

Macrophages are required for adult salamander limb regeneration

Effects of 6-hydroxydopamine on the Adult Neurogenesis of Dopaminergic Neurons in the Mouse Midbrain

Contact Info

Product

Resources

About