Neuroarcheology: presymptomatic architecture and electrical signature of neurological disorders
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1
Institute of Neurobiology of the Mediterranean Sea (INMED), INSERM, Campus Scientifique de Luminy, Route de Luminy, France
Brain development is organised around a genetic program that controls the proliferation, migration and neuronal growth and formation of synaptic connections with the assigned targets. However, all these steps are also controlled by the environment and notably the neuronal activity that the systems generate during construction. Therefore, alterations of the genetic program and of neuronal activity can lead to major alterations of network construction associated with profound deleterious sequels. It is suggested here that these early insults whether they are due to program errors or environmental hazards can be manifested presymptomatically well before the neurological disorder is installed and visible. This has important conceptual and clinical implications as well as numerous openings as to future research directions. The arguments in favour of this theory are as follows: i) Immature neurons are highly fragile and sensitive to insults but in contrast to adult neurons, do not readily degenerate. Thus, early seizures or anoxic episodes in pups produce long-term sequels without causing damage to neurones at least until the end of the end week postnatal. This suggests that the traces that lead from the insult to the late sequels are not due to the classical adult sequence – cell loss and reactive reorganisation – but to a modification of the program that is subliminal. ii) Recent studies using in utero SRNAi transfections show that invalidating at an early stage a protein that is known to play a crucial role in brain development and is associated with a specific neurological disease leads to early malformation. A wide range of disorders are now being investigated including early (Double cortex and a variety of early epilepsies) but also late ones such as Huntington or Alzheimer disease and early malformations are conspicuous in this model. Perhaps more impressively, imaging studies in pre-symptomatic young patients with Huntington mutations – well before the first clinical sings are apparent have brain malformations. Collectively, these studies call for a reinvestigation of the links between insults and brain disorders and of the timing of operation of neurological disorders.Interestingly, recordings from misplaced neurons show that they are frozen in an immature state with immature ionic channels suggesting that the aberrant patterns that they generate and that impinge on the operation of these circuits may be amenable to selective drug treatment.
References
1. Ben-Ari Y, (2007). Neuro-archaeology: pre-symptomatic architecture and signature of neurological disorders, Trends in Neurosciences, 31 (12): 626 - 636.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Plenary lectures
Citation:
Ben-Ari
Y
(2009). Neuroarcheology: presymptomatic architecture and electrical signature of neurological disorders.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.007
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Received:
18 Nov 2009;
Published Online:
18 Nov 2009.
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Correspondence:
Yehezkel Ben-Ari, Institute of Neurobiology of the Mediterranean Sea (INMED), INSERM, Campus Scientifique de Luminy, Route de Luminy, Marseille 13263 Cedex, France, ben-ari@neurochlore.fr