An important mechanism responsible for clinical recovery after neurological damage of
different types is synaptic plasticity. Nervous tissue can enhance or de-energize
inter-neuronal transmission at synaptic level in a lasting way. By increasing the efficiency
of synaptic transmission, through long-term potentiation (LTP), it is possible to compensate
for the loss of synaptic pulses on survived neurons due to brain damage and to restore their
function.
At synaptic level, LTP is mainly regulated by NMDA receptors. In animal models induction of
plasticity in surviving neurons through the stimulation of NMDA receptors has been shown to
limit the clinical manifestations of neuronal damage. Endogenous NMDA is synthesized by
methylation of D-aspartate (Asp) by D-aspartatoartate methyltransferase . Moreover, Asp acts
as a neurotransmitter capable of activating the NMDA receptor, since its biosynthesis,
degradation, absorption and release occurs in the pre-synaptic neuron, and its release
determines a response in Post-synaptic neurons. The expression of Asp in the SNC is very
abundant during the embryonic period and in early years, whereas it is significantly reduced
in adulthood.
Consistent with Asp ability of activating the NMDA receptor, recent studies have shown that
oral administration of Asp increases LTP induction in mice. Preliminary studies by our group
also showed an increase in LTP amplitude in subjects suffering from progressive forms of
Multiple Sclerosis after 2 weeks of daily per os intake of 2660mg Asp.
It is also well known that the therapeutic exercise that characterizes a rehabilitative
treatment is able to induce various benefits to the physical-functional and the
cognitive-emotional spheres. In this regard, it has been extensively demonstrated how
repeatedly performing a motor task can increase cortical excitability through the induction
of LTP mechanisms.
Hypothesis Pharmacologically promoting the induction of cortical LTP by the intake of Asp in
subjects with various types of brain damage (eg Multiple Sclerosis, Parkinson's Disease,
Dementia) may favor the therapeutic effects of rehabilitative treatment.
Specific Objectives Evaluate the effects of Asp in improving the outcome of rehabilitative
treatment resulting from brain damage of different origin.