Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, I.; Sequerra, Eduardo

doi:10.1016/j.neuropharm.2012.12.005

Cited by 20 publications

(16 citation statements)

References 59 publications

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“…In the case of the earlier stage fetal development following more complex anterior-posterior differentiation of the neural tube and the establishment of prosencephalon, mesencephalon, and rhombencephalon, more distinct neuronal populations begin to emerge due to specific morphogen combinations and temporal sequences of exposure [142,143], with certain regions producing environmental signals conducive to specific neuronal subtypes. As glutamatergic neurons distinguish from GABAergic neurons within regionally distinct sub-areas of the subventricular source of new neurons, basic helix-loop-helix transcription factors are induced to kick in, such as neurogenins, leading to a glutamatergic fate, and Mash-1 along with the "distal less" homeodomain genes presumably induced into expression by positional signals Dlx1 and Dlx2 that seem to promote a GABAergic fate, with the degree of initial neurogenin or Mash-1 expression a seemingly deciding factor [144].…”

Section: Adaptation Of Transplanted Neural Cells To the Endogenous Homentioning

confidence: 99%

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Sandstrom¹,

Anderson²,

Jayaprakash³

et al. 2018

Neuroplasticity - Insights of Neural Reorganization

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Although stem cell transplant therapy offers considerable promise for deteriorative diseases, the efficacy of its application may be mitigated by endogenous compensatory mechanisms in the host brain. Plastic compensation follows neurodegeneration, beginning at its very onset and minimizing early symptom expression. As researchers attempt to correlate symptom remission with the ability of transplanted cells to adopt specific cell phenotypes, they need to be vigilant of the possibility that competing, local compensatory effects may be altering the outcome. Clearly plastic compensatory mechanisms could confound desired transplant-derived improvements by supplanting the beneficial contributions of the transplants. As circuit-level adaptations occur, more explicit explorations of their relevance to neuronal transplantation success are needed. Conceptual models of undirected transplanted cells adopting preconceived appropriate roles require revision. The notion that newly transplanted neuronal precursors will incorporate themselves into host circuitry with mutual cooperation across both parties (i.e., transplant and host) without some symbiosis-promoting mechanism is naïve. Undirected local circuits could react to newly transplanted additions as intruders. We advocate that appropriate signaling from transplanted cells to the host environment is required to optimize the therapeutic relevance of transplantation. This review surveys critical signaling mechanisms that might promote symbiotic interdependence between the host and new transplants.

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Section: Adaptation Of Transplanted Neural Cells To the Endogenous Homentioning

confidence: 99%

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Sandstrom¹,

Anderson²,

Jayaprakash³

et al. 2018

Neuroplasticity - Insights of Neural Reorganization

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“…This "modern version of Dale`s principle" claimed that neurons release the same set of transmitters from all of their axon processes, assuming that the identity of the transmitters expressed by neurons is unchanging. Nevertheless, recent discoveries [16,17,18] demonstrate that electrical activity can respecify neurotransmitter expression during development, but also in mature nervous system. The logical question that arises is what happens with postsynaptic receptors if the identity of presinaptically created neurotransmitter changes.…”

Section: Lost In Translationmentioning

confidence: 99%

Neurotransmitters in the central nervous system: Basic knowledge revisited

Lozic-Djuric¹

2015

Med podmladak

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The chemistry within us This elegant experiment performed by Otto Loewi is considered to be the Rosetta stone of chemical transmission concept and has provided the first evidence that nerves do not influence the heart directly, but liberate specific chemical substances from their terminals. Today, when neurotransmitters are inseparable part of theories of how our brain works, it is difficult to understand that it took more than thirty years of scientific disputes between neurophysiologists and pharmacologists to prove that synaptic transmission is chemical rather than electrical. The great victory of pharmacologists in a war called "the war of sparks and soups" [2,3] happened in 1936, when Otto Loewi and Sir Henry Dale were awarded the Nobel Prize for establishing chemical synaptic transmission.Given the fact that acetylcholine was the first neurotransmitter to be discovered [4], it is not surprising that the classic criteria for neurotransmitters were based on the properties of this particular molecule.Although conventional definition describes a neurotransmitter as a substance that satisfies the following criteria [5,6]:1. It is synthesized and stored within the presynaptic neuron 2. It is released by nerve stimulation in a calcium-dependent manner 3. It binds to specific receptor(s) localized presinaptically or postsinaptically 4. Its exogenous application mimics the postsynaptic effect of presynaptic stimulation 5. Specific receptor antagonists block the effects of endogenous (synaptically released) or exogenous (externally applied) substance 6. Its action(s) can be terminated in enzyme-mediated way or by the cellular uptake mechanism, the increasing knowledge in the field of neuroscience has been continually modifying the understanding of the term "neurotransmitter". Nowadays, we are faced with at least two questions that may sound like a rather perplexing word game, but still need to be properly addressed: Are only neurotransmitters-neurotransmitters? Are neurotransmitters only neurotransmitters?

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“…The features that define a specific neuronal phenotype are generally conserved between species, are specified early during development, but can also undergo adaptive plasticity related to activity after maturation (Demarque and Spitzer, 2012;Borodinsky et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis inXenopus

Lambert

Cardoit

Courty

et al. 2017

Preprint

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In vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine.Generally, motoneurons and muscles develop simultaneously during embryogenesis.However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system.Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity.Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre-and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent respecification of neurotransmitter phenotype during neuromuscular system development.

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Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

Cited by 20 publications

References 59 publications

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Neurotransmitters in the central nervous system: Basic knowledge revisited

Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis inXenopus

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