3. Umbruch 4.4..2005 - Online Pot

Cannabinoids in neurodegeneration and neuroprotection 99
relief. In this sense, a recent study by Pryce and coworkers [184] has demonstrated
that CB 1 receptor-deficient mice tolerated inflammatory and excitotoxic
insults poorly and developed substantial degeneration following immune
attack in EAE.
Despite the progress in the pharmacological evaluation of cannabinoid-based
medicines in MS in patients and animal models, there are no data on the possible
changes in CB 1 and CB 2 receptors in the postmortem brain of patients with
MS, while only a few studies have examined the status of the endocannabinoid
transmission in animal models of this disease [128, 188, 191]. Thus, Baker and
coworkers reported an increase of endocannabinoid levels in the brain and, in
particular, in the spinal cord in the mouse model of MS [128], that was interpreted
by these authors as indicative of an endocannabinoid influence on the
control of some symptoms of MS in an environment of existing neurological
damage (see [76] for review). In our laboratory, using EAE rats, we recently
reported a decrease of CB 1 receptor binding and mRNA levels [191], although
the decreases in CB 1 receptors were mainly circumscribed to the basal ganglia
(lateral and medial caudate-putamen), and to a lesser extent to cortical regions.
We have also recorded a reduction of endocannabinoid levels in these and in
other brain structures [188]. However, as the pathology in MS models mainly
occurs in the spinal cord, the relevance of the observations in the basal ganglia
remains to be elucidated, although it is possible that they are a secondary adaptative
event originated by primary changes at the spinal level. Thus they might
be related to the motor deterioration which is one of the most prominent neurological
signs in these rats [188, 191] and also in the human disease [76, 183].
Based on this fact, we hypothesized that the changes in CB 1 receptors and their
ligands in the basal ganglia might be associated with disturbances in several
neurotransmitters acting at this circuitry. If this were the case, the well-known
effects of cannabinoid agonists on these neurotransmitters might underly the
improving effects of these compounds in motor symptoms of MS (see [7, 27]
for review). However, our hypothesis was wrong because we did not record any
changes in dopamine, serotonin (5-hydroxytryptamine), GABA or glutamate in
the basal ganglia of MS rats [188].
ALS
ALS is one of the most common neurodegenerative disorders, occurring both
sporadically and as a familial disorder with demonstrated inherited cases in
about a 10% of patients. Although it shows multiple clinical variants, it is characterized
by degeneration of spinal motor neurons primarily and cortical neurons
secondarily (see [122, 123] for recent reviews). Neuronal loss occurs
from a combination of metal-elicited oxidative injury, excitotoxicity, aggregation
and/or dysfunction of critical proteins, and genetic factors [122, 123].
Classic therapy in this disease includes riluzole, an inhibitor of glutamate
release and sodium channel blocker, but it is unsatisfactory and does not arrest