Biochemical, histopathological and behavioral alterations caused by intrastriatal administration of quinolic acid to young rats.

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, and is considered to be involved in aging and some neurodegenerative disorders, including Huntington's disease. QUIN was injected intrastriatally into adolescent rats, and biochemical and histopathological analyses in the striatum, cortex, and hippocampus, as well as behavioral tests, were carried out in the rats over a period of 21 days after drug injection. Decreased [(3)H]glutamate uptake and increased (45)Ca(2+) uptake were detected shortly after injection in the striatum and cerebral cortex. In the hippocampus, increased (45)Ca(2+) uptake preceded the decreased [(3)H]glutamate uptake, without histopathological alterations. Also, corticostriatal astrogliosis was observed 7 days later, progressing to neuronal death at day 14. QUIN-treated rats also showed cognitive deficits 24 h after injection, concurrently with striatal astrogliosis. Motor deficits appeared later, after corticostriatal neurodegeneration. We assume that glutamate excitotoxicity could represent, at least in part, a molecular mechanism associated with the cognitive and motor impairments, corticostriatal astrogliosis and neuronal death observed in the QUIN-treated rats. We propose that our findings could be relevant for understanding the pathophysiology of human neurodegenerative diseases affecting young people, such as the juvenile form of Huntington's disease, and for the design of potential therapeutic strategies to slow down the progression of the disease.

Treadmill training induces plasticity in spinal motoneurons and sciatic nerve after sensorimotor restriction during early postnatal period: new insights into the clinical approach for children with cerebral palsy.

The aim of the present study was to investigate whether locomotor stimulation training could have beneficial effects on the morphometric alterations of spinal cord and sciatic nerve consequent to sensorimotor restriction (SR). Male Wistar rats were exposed to SR from postnatal day 2 (P2) to P28. Control and experimental rats underwent locomotor stimulation training in a treadmill for three weeks (from P31 to P52). The cross-sectional area (CSA) of spinal motoneurons innervating hind limb muscles was determined. Both fiber and axonal CSA of myelinated fibers were also assessed. The growth-related increase in CSA of motoneurons in the SR group was less than controls. After SR, the mean motoneuron soma size was reduced with an increase in the proportion of motoneurons with a soma size of between 0 and 800 µm(2). The changes in soma size of motoneurons were accompanied by a reduction in the mean fiber and axon CSA of sciatic nerve. The soma size of motoneurons was reestablished at the end of the training period reaching controls level. Our results suggest that SR during early postnatal life retards the growth-related increase in the cell body size of motoneurons in spinal cord and the development of sciatic nerve. Additionally, three weeks of locomotor stimulation using a treadmill seems to have a beneficial effect on motoneurons' soma size.