Neuroscience
-
Basal forebrain neurons express the neurotrophin receptors, p75NTR and tyrosine kinase receptor A (TrkA). We tested the hypothesis that impairment of memory in rats could be achieved by RNA interference (RNAi) -induced silencing of TrkA specifically within these neurons. A novel fusogenic, karyophilic immunoporter (fkAb(p75)-ipr) was constructed from the antibody, MC192 (monoclonal antibody to the rat neurotrophin receptor p75NTR, Ab(p75)), poly-l-lysine together with the hemagglutinin 2 and VP1 nuclear localization peptides of influenza and SV40 virus, respectively. ⋯ Animals that received TrkAi-fkAb(p75) showed significantly impaired spatial memory learning ability compared with naive or TrkAsc-fkAb(p75)-treated rats. Western blot and immunofluorescence analysis showed that TrkA protein levels and numbers of TrkA positive neurons were reduced by 60% and 55% respectively in TrkAi-fkAb(p75)-infused rats compared with infused controls or naive animals. We conclude that p75-receptor-mediated RNAi-induced silencing of genes offers a novel and powerful way to study the function of specific endogenous genes within distinct neuronal subpopulations of the brain.
-
Clinical Trial
Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans.
The present study investigated the effects of exercise on the serum concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), prolactin (PRL) and cortisol (COR) in 11 chronically spinal cord-injured athletes. In these subjects BDNF concentration at rest was sixfold higher compared with the concentrations reported earlier in able-bodied persons, while IGF-1, PRL and COR were within normal range. Ten minutes of moderate intensity handbiking (54% of the maximal heart rate) during a warm-up period (W) induced an increase (P<0.05) of BDNF of approximately 1.5-fold from basal level at rest, while a decrease to basal level was found after an immediately succeeding handbiking time trial (89% of the maximal heart rate) over the marathon distance of 42 km (M). ⋯ The augmented PRL concentration suggests that a possible mechanism by which exercise promotes neuroplasticity might be the activation of neural serotonergic pathways as 5-HT is the main PRL releasing factor. Elevated COR concentrations after M are unlikely to be deleterious to neuroplasticity as COR concentrations remain within the physiological range. The present study suggests that exercise might be beneficial to enhance neuroprotection and neuroplasticity, thereby improving recovery after spinal cord injury.
-
The beneficial effects of caffeine on cognition are controversial in humans, whereas its benefit in rodents had been well characterized. However, most studies were performed with acute administration of caffeine and the tasks used to evaluate cognition had aversive components. Here, we evaluated adulthood administration of caffeine up to old age on recognition memory in mice using the object recognition task (ORT) and on brain-derived neurotrophic factor (BNDF) and tyrosine kinase receptor (TrkB) immunocontent in the hippocampus. ⋯ Caffeine also counteracted the age-related increase in BDNF and TrkB immunocontent. Our results corroborate with other studies and reinforce that caffeine consumed in adulthood may prevent recognition memory decline with aging. This preventive effect may involve a decrease in the hippocampal BDNF and TrkB immunocontent.
-
A continuous supply of fusion-competent synaptic vesicles is essential for sustainable neurotransmission. Drosophila mutations of the dicistronic stoned locus disrupt normal vesicle cycling and cause functional deficits in synaptic transmission. Although both Stoned A and B proteins putatively participate in reconstituting synaptic vesicles, their precise function is still unclear. ⋯ Therefore, we conclude that STNB not only functions as an essential component of the endocytic complex for vesicle reconstitution, as previously proposed, but also regulates the competence of recycled vesicles to undergo fusion. In support of such role of STNB, synaptic levels of the vesicular glutamate transporter (vGLUT) and synaptotagmin-1 are strongly reduced with diminishing STNB function, while other synaptic proteins are largely unaffected. We conclude that STNB organizes the endocytic sorting of a subset of integral synaptic vesicle proteins thereby regulating the fusion-competence of the recycled vesicle.
-
The c-kit receptor tyrosine kinase is expressed in a subpopulation of small- and medium-sized neurons of the dorsal root ganglia (DRG) and in the superficial layer of the spinal cord. Stem cell factor (SCF), a ligand of the c-kit receptor, induces neurite outgrowth from DRG and supports the survival of c-kit-expressing neurons. To clarify the possible function of the SCF/c-kit receptor system in the adult animal, we investigated the expression of c-kit receptor in the spinal cord and DRG in relation to pain by using H2C7, a newly developed anti-c-kit monoclonal antibody. ⋯ Selective elimination of unmyelinated C-fibers by neonatal capsaicin treatment resulted in marked reduction of the c-kit receptor and CGRP expression in the superficial layer of the spinal cord. Cell-size profiles showed that c-kit receptor expression was significantly up-regulated and down-regulated in medium-sized DRG neurons after neonatal capsaicin treatment and nerve injury, respectively. These results suggest that the c-kit receptor is mainly expressed in peptidergic small-sized DRG neurons and may be involved in pain regulation both peripherally and centrally.