No abstract

Previous evidence indicates that locomotor exercise is a powerful means of increasing brain-derived neurotrophic factor (BDNF) and its signal transduction receptor TrkB mRNA levels, immunolabeling intensity and number of BDNF- and TrkB-immunopositive cells in the spinal cord of adult rats but the contribution of specific cell types to changes resulting from long-term activity is unknown. As changes in BDNF protein distribution due to systemic stimuli may reflect either its in-situ synthesis or its translocation from other sources, we investigated where BDNF and TrkB mRNA are expressed in the spinal lumbar segments. We report on the cell types defined by size, BDNF mRNA levels and number of cells with TrkB transcripts in sedentary and exercised animals following 28 days of treadmill walking. In the majority of cells, exercise increased perikaryonal levels of BDNF mRNA but did not affect TrkB transcript levels. Bidirectional changes in a number of TrkB mRNA-expressing cells occurred in small groups of ventral horn neurons. An increase in BDNF transcripts was translated into changes in pro-BDNF and BDNF levels. A 7-day walking regimen increased BDNF protein levels similarly to 28-day treadmill walking. Our observations indicate that long- and short-term locomotor activity of moderate intensity produce stimuli sufficient to recruit a majority of spinal cells to increased BDNF synthesis, suggesting that continuous tuning of pro-BDNF and BDNF levels permits spinal networks to undergo trophic modulation not requiring changes in TrkB mRNA supply.

In situ hybridization was used to evaluate whether long-term moderate locomotor exercise, which up-regulates BDNF and TrkB levels in the spinal gray matter of the adult rat, similarly influences the expression of the cell adhesion molecules N-CAM and L1. Exercise doubled the level of N-CAM mRNA hybridization signal in the lumbar spinal gray. The increase in L1 mRNA was less consistent. N-CAM mRNA levels slightly increased in the white matter. BDNF mRNA levels also increased in cells of the ventral horn and the white matter due to the exercise. These results suggest that exercise-induced rearrangements of the spinal network involve N-CAM, L1 and BDNF, crucial in different aspects of synaptic plasticity and synapse formation.

assessed using the Hamilton Rating Scale for Depression (HAM-D). Response equaled at least a 50% decrease in the baseline HAM-D 21-item score. Remission equaled a HAM-D l7-item score of 7 or less. Differences between venlafaxine, SSRIs, and placebo for gender and age subpopulations were determined using Fisher's exact test.Results: Outcomes with each treatment were similar for all subpopulations. In both genders, venlafaxine and SSRI remission rates were superior to placebo at week 8 (all P < 0.05); additionally, venlafaxine had a higher remission rate than SSRIs in these subpopulations. With venlafaxine, response was more rapid (week 2 vs placebo, P < 0.02); by week 8, response rates were higher (61% to 79%) than with SSRls (51% to 62%) [P < 0.011.Conclusions: These data may suggest that depressed patients of both genders and ages respond similarly to available pharmacotherapies. Moreover, a more rapid response and remission are likely with venlafaxine.