Molecules to repair the brain

The plastic capability of our brain is at the basis of the cognitive abilities that are distinctive of humans. Cerebral plasticity is also at the basis of the attempts to recovery functions lost because of vascular or traumatic lesions of the brain. Unfortunately, as demonstrated by the deficits present in patients affected by these pathologies, these attempts even if present are scarcely effective. However, if the lesion occurs during childhood, when the brain is still highly plastic, there is an activation of plastic rearrangements of the structure of neural circuits that lead to the preservation of the cerebral function which would be lost or severely compromised if the same lesion had occurred in adults. This observation underscores the necessity to identify the molecular mechanisms that reduce cerebral plasticity in the adult brain and raises the possibility to use this knowledge to devise therapeutical strategies to reinstate in the adult brain levels of plasticity typical of the child.
In our study(Science 2002, 298:1248-51)we examined plasticity in the visual cortex of the rat. In this animal, as in other mammals including humans, deprivation of vision during development causes a strong deficits of visual performance of the deprived eye that becomes short-sighted (amblyopia). In the adult, the reduced plasticity of visual cortical circuits makes the visual cortex unresponsive to monocular deprivation.
In our study we hypothesized that that the scarce malleability of adult cortical circuits was due to the presence in the space that separate neurons of molecules that inhibit the formation or the rearrangement of synapses. It was already known that glycoproteins of the extracellular matrix (Chondroitinsulphate proteoglycans or CSPGs) are inhibitory for the growth of the part of the neuron that forms synapses, i.e. the axon.
In our experiments we verified that the injection with Chondroitinase ABC, an enzyme that degrades CSPGs, of the visual cortex of adult monocularly deprived rats reactivates the levels of plasticity typical of the young cortex.
This study individuates a class of molecules, the CSPGs, that could be targeted pharmacologically to reactivate plasticity in the adult visual cortex. CSPGs are present also in other brain structures suggesting that CSPG removal could be effective in reactivating the juvenile levels of plasticity not only in the visual cortex, but also in other brain areas.
Future studies will demonstrate if the removal of CSPGs will be able to facilitate functional recovery not only from amblyopia but also from cerebral lesions.

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