ABSTRACT
Abstract The cannabinoid chemistry is currently being addressed in preclinical approaches as a viable therapeutic alternative for the management of a wide range of signs, symptoms, and some biochemical hallmarks of many neurological pathologies (such as neuroinflammation and neurodegeneration). This clinical orientation is grounded on the consistent promissory profile that cannabinoid compounds have shown, and the great necessity of feasible options to undergo such disorders. Even though at early research stages, metabolic disorders are starting to rise as potential targets of cannabinoid alternatives; approaches in this term could, in turn, aim to modulate the endocannabinoid response for therapeutic purposes. This review recalls the pathologic scenarios endured in the course of neurological diseases of high occurrence and the most typical metabolic disorders, while discussing the neuroprotective mechanisms of cannabinoid agonists in the central nervous system, and the potential targets of the endocannabinoid system and metabolic disorders.
ABSTRACT
Total copper and manganese contents were measured in five rat brain regions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1µl), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace atomic absorption spectrophotometry. Increases in copper content were observad after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152 percent as compared against control values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35 percent vs. control values, but not in all other brain regions analyzed. QUIN-induced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23 percent vs. control, respectively) by pretreatment of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN microinjection. The same protective effect of fizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45 percent vs. control). These findings resemble those changes observed in postmortem Huntington's disease brain and suggest that alterations in regional content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tissue to the neighboring regions of the brain, by action of QUIN on NMDA receptors