Abstract
The recognition of internal and external sources of stimuli, the self from non-self, seems to be an intrinsic property to the adequate functioning of the immune system and the nervous system, both complex network systems that have evolved to safeguard the self biological identity of the organism. The mammalian brain development relies on dynamic and adaptive processes that are now well described. However, the rules dictating this highly constrained developmental process remain elusive. Here we hypothesize that there is a cellular basis for brain selfhood, based on the analogy of the global mechanisms that drive the self/non-self recognition and instruction by the immune system. In utero education within the thymus by multi-step selection processes discard overly low and high affinity T-lymphocytes to self stimuli, thus avoiding expendable or autoreactive responses that might lead to harmful autoimmunity. We argue that the self principle is one of the chief determinants of neocortical brain neurogenesis. According to our hypothesis, early-life education on self at the subcortical plate of the neocortex by selection processes might participate in the striking specificity of neuronal repertoire and assure efficiency and self tolerance. Potential implications of this hypothesis in self-reactive neurological pathologies are discussed, particularly involving consciousness-associated pathophysiological conditions, i.e., epilepsy and schizophrenia, for which we coined the term autophrenity.
Highlights
A basic question of immunology has been the recognition of self from non-self in vertebrates, since the theory proposed by Burnet and Fenner (1949)
We have developed a mechanistic hypothesis of self recognition in the brain at the cell level from an immunological perspective
The theoretical development of this hypothesis has led us to the proposition of a thymus-like model of cortical neurogenesis based on this scenario
Summary
A basic question of immunology has been the recognition of self from non-self in vertebrates, since the theory proposed by Burnet and Fenner (1949). The thymus is the central organ of immunologic self/non-self discrimination and of the induction of tolerance (i.e., non responsiveness) to most self antigens, in line with the generation of high T-lymphocyte diversity on grounds of more specific and efficient response This comes at the price of potentially harmful autoimmunity, which would lead to autoimmune disease affecting any cell or tissue, such as multiple sclerosis or diabetes mellitus. One of the principles underlying neocortical expansion has been the increase in neuronal generation, mainly at the expense of highly proliferative basal progenitors typically in the subventricular zone (SVZ) (Lui et al, 2011) As mentioned above, this immune-based analogy does not pretend to explain emergent brain processes accounting for intelligence, the complex human behavior and the set of properties that we call mind (mental self), which are currently not completely covered by neurobiology, but beyond, by psychology and sociology. Until we know more about the specific requirements for such recognition, we could
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