Cerebral plasticity, the capacity of central nervous system to change itself in response to various biological and environmental conditions, represent one of most important acquisition of contemporary neuroscientific research. In pathogenic field three types of plasticity are described. The first is “adaptive” plasticity, which is involved in learning or recovery from a trauma; the second is “compromised” plasticity, deriving from cerebral damage linked to a neuropsychic genic disorder; the third is “maladaptive” plasticity, which consists of a regenerative dysfunctional reaction and leads to the development of a new disorder; the fourth is a plasticity named “the Achille’s heel of the brain”, which refers to some specific neuronal vulnerabilities. The basic mechanisms of plasticity consist of: an overproduction of cells, the subsequent reduction in apoptosis (programmed cellular death), a differentiation of new cells starting from stem elements of the hippocampus and the cerebral ventricles, a dependent section of the neurotransmitters activity, the growth factor product by the brain and synapsis, and an epigenetic modulation (a way in which the environment alters the activity degree of the genes without modifying the information) of the DNA expression. In 2012 the Hugo Moser Institute and John Hopkins University of Baltimore (USA) investigated the relationship between the anomalies of the neuronal plasticity mechanisms and the MTOR gene activity in tuberous sclerosis, neurofibromatosis 1, fragile X syndrome, and Cowden syndrome, which represent some of the principal neurogenic disorders. The mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin is a kinase that in humans is encoded by the MTOR gene and participates in the regulation of different cellular processes. In particular it regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. The research found that the above mentioned syndromes present interesting similarities not only with respect to the impairment of the neuroplasticity mechanisms and mTOR upsetting, but also in relation to the clinical aspects: intellectual disability, autistic features, cutaneous injuries, and cancers. The most important results indicate that early intervention on mTOR activity could change these conditions (as well as similar syndromes), which contests the previously held belief that these conditions were irreversible. In 2016 Sato (Department of Pediatrics, University of Tokyo) reviewed the literature on this topic and confirmed that evidence is accumulating that mTOR inhibitors mostly rescue these neuronal and behavioral alterations in rodent models of autism. On the basis of this, new translational research is expected to elucidate the therapeutic efficacy of mTOR inhibitors for autism spectrum and intellectual developmental disorders in the near future.
REFERENCES
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- Gipson TT, Johnston MV. Plasticity and mTOR: Towards Restoration of Impaired Synaptic Plasticity in mTOR-Related Neurogenetic Disorders. Neural Plast. 2012;2012:486402. Epub 2012 Apr 30.
- Sato A. mTOR, a Potential Target to Treat Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2016;15(5):533-43.