Neuroprotection

This study examined the acute and chronic responses of brain-derived neurotrophic factor (BDNF), cathepsin B (CatB), insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) and if changes in these biomarkers were correlated during resistance training. Fourteen resistance trained men performed resistance training 3 days per week for 6 weeks in two groups. The only difference between groups was the proximity to failure of each set (4-6 repetitions in reserve or 1-3 repetitions in reserve). Serum was collected immediately before and after training on day 1 of weeks 1 and 6.
There were no significant group interactions for any of the biomarkers assessed, there were no main effects for time (p>0.05), and no significant correlations were observed between any of the biomarkers. However, a significant main effect for exercise for BDNF (p=0.03) and IL-6 (p=0.003) was observed. For CatB, a significant exercise × time (p=0.002) interaction was observed, indicating differences in the acute change of CatB in week 6 (+15.78%; g=0.25) vs. week 1 (-7.46%; g=0.13). In summary, these results suggest that multi-joint resistance exercise far from failure can confer a BDNF response. This investigation is the first to demonstrate the potential for acute resistance exercise to elicit a transient increase in CatB.

This study examined if multi-joint resistance exercises could elicit expression of biomarkers associated with neuroprotection. Thirteen well-trained males performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the back squat, bench press, and deadlift. The biomarkers measured immediately pre- and post-exercise were brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). There was a main time effect (p<0.01) for BDNF with significant increases in the deadlift (p=0.01) and bench press (p=0.01) conditions, but not the squat (p=0.21). There was a main time effect (p<0.01) for IL-6 with a significant increase in the squat (p<0.01). There was no significant increase in CatB or IGF-1 (p>0.05). Additionally, there was no significant relationship between BDNF and IL-6 response.

The human brain functions within a narrow range of temperatures and
variations outside of this range incur cellular damage and death and, ultimately,
death of the organism. Other organisms, like the poikilotherm Drosophila
melanogaster, have adapted mechanisms to maintain brain function over wide
ranges in temperature and, if exposed to high temperatures where brain function
is no longer supported, these animals enter a protective coma to promote survival
of the organism once the acute temperature stress is alleviated.
This research characterized the role of different neuronal cell types,
including glia, in the protection of brain function during acute hyperthermia,
specifically looking at two protective pathways: the heat shock protein (HSP)
pathway and the cGMP-dependent protein kinase G (PKG) pathway. Whole
animal behavioral assays were used in combination with tissue-specific genetic
manipulation of protective pathways to determine the specific cell types sufficient to confer protection of neuronal function during acute hyperthermia. Using the
neuromuscular junction (NMJ) preparation, calcium imaging techniques were
combined with pharmacological and genetic manipulations to test the hypothesis
that alterations in ion channel conductance via endogenous mechanisms
regulating the cellular response to high temperature stress alter neuronal function.
Expression of foraging RNAi to inhibit PKG expression in neurons or glia
demonstrated protection of function during acute hyperthermia measured
behaviorally through the extension of locomotor function. This extension of
function with the tissue-specific inhibition of PKG was also confirmed at the cellular
level using the genetically encoded calcium indicator (GECI), GCaMP3, to image
calcium dynamics at the NMJ, where preparations expressing foraging RNAi could
continue to elicit changes in calcium dynamics in response to stimulation. Over
the course of this study, the mechanism underlying a novel glial calcium wave in
the peripheral nervous system was characterized in order to elucidate glia’s role in
the protection of neuronal function during acute hyperthermia.