No abstract

Ciliary neurotrophic factor (CNTF) is a cytokine that plays a neuroprotective role in relation to axotomized motoneurons. We determined the effect of daily subcutaneous doses of CNTF (1.2 µg/g for 5 days; N = 13) or PBS (N = 13) on the levels of mRNA for Bcl-2 and Bax, as well as the expression and inter-association of Bcl-2 and Bax proteins, and the survival of motoneurons in the spinal cord lumbar enlargement of 2-day-old Wistar rats after sciatic nerve transection. Five days after transection, the effects were evaluated on histological and molecular levels using Nissl staining, immunoprecipitation, Western blot analysis, and reverse transcriptase-polymerase chain reaction. The motoneuron survival ratio, defined as the ratio between the number of motoneurons counted on the lesioned side vs those on the unlesioned side, was calculated. This ratio was 0.77 ± 0.02 for CNTF-treated rats vs 0.53 ± 0.02 for the PBS-treated controls (P < 0.001). Treatment with CNTF modified the level of mRNA, with the expression of Bax RNA decreasing 18% (with a consequent decrease in the level of Bax protein), while the expression of Bcl-2 RNA was increased 87%, although the level of Bcl-2 protein was unchanged. The amount of Bcl-2/Bax heterodimer increased 91% over that found in the PBS-treated controls. These data show, for the first time, that the neuroprotective effect of CNTF on neonatal rat axotomized motoneurons is associated with a reduction in free Bax, due to the inhibition of Bax expression, as well as increased Bcl-2/Bax heterodimerization. Thus, the neuroprotective action of the CNTF on axotomized motoneurons can be related to the inhibition of this apoptotic pathway.

The present study investigated whether the sensitization to acoustic stimuli in pigeons oscillates as a function of the time of day. Both the training and testing were conducted in a single session and the procedure was repeated every 4 h with different experimental and control groups of pigeons. A skeleton photoperiod (two 15-min light pulses to indicate the beginning and the end of the day) was used to prevent the masking effects of the light-dark cycle. The procedure consisted of a baseline exposure to five tone pulses, sensitization training with two electric shocks (5 min interval) starting 5 min later and testing using a series of 40 tone pulses, starting 10 min later. The control birds were exposed to the chamber only. The magnitude of response was measured by an accelerometer located under the floor of the experimental chamber. Sensitization was analyzed by comparing the amplitude of the response during testing to the baseline level. The amplitude of response of the experimental birds varied as a function of the time of day, with significantly greater amplitude during the subjective night (P 5 0.05). Control data showed no daily variation, however, suggesting that the rhythm in sensitization was due to the circadian modulation of a learning process.