Neuroscience
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The prefrontal cortex is continuously required for working memory processing during wakefulness, but is particularly hypoactivated during sleep and in psychiatric disorders such as schizophrenia. Ammon's horn CA1 hippocampus subfield (CA1) afferents provide a functional modulatory path that is subjected to synaptic plasticity and a prominent monoaminergic influence. However, little is known about the muscarinic cholinergic effects on prefrontal synapses. ⋯ Monoamine levels were specifically altered in the mPFC. We observed a decrease in dopamine, 5-HT, 5-hydroxyindolacetic acid and noradrenaline levels, with no changes in 3,4-hydroxyphenylacetic acid levels. Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes.
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Both mu- and delta-opioid agonists selectively inhibit nociception but have little effect on other sensory modalities. Voltage-activated Ca(2+) channels in the primary sensory neurons are important for the regulation of nociceptive transmission. In this study, we determined the effect of delta-opioid agonists on voltage-activated Ca(2+) channel currents (I(Ca)) in small-diameter rat dorsal root ganglion (DRG) neurons that do and do not bind isolectin B(4) (IB(4)). ⋯ Additionally, DPDPE significantly inhibited high voltage-activated I(Ca) in Tyrode's or N-methyl-d-glucamine solution but not in tetraethylammonium solution. This study provides new information that delta-opioid agonists have a distinct effect on voltage-activated Ca(2+) channels in different phenotypes of primary sensory neurons. High voltage-activated Ca(2+) channels are more sensitive to inhibition by delta-opioid agonists in IB(4)-negative than IB(4)-positive neurons, and this opioid effect is restricted to DRG neurons devoid of functional T-type Ca(2+) currents.
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We here investigated the effects of neonatal lesions of the entorhinal cortex (EC) in rats on maze learning and on structural alterations of its main projection region, the hippocampus, as well as other regions with anatomical connections to the EC that are involved in maze learning. Since early brain damage is considered to be involved in certain neuropsychiatric diseases, this approach sought to model certain aspects of this etiopathogenesis. Bilateral neonatal lesions were induced on postnatal day 7 by microinjection of ibotenic acid (1.3 microg/0.2 microl phosphate-buffered saline (PBS)) into the EC. ⋯ Histological evaluation revealed that the density of parvalbumin-immunopositive neurons and myelin sheaths was reduced in the hippocampus but not in the striatum and mPFC in neonatally lesioned rats. Density of MAP-2 staining did not differ between groups in all regions tested. Since structural alterations were only found in the EC and hippocampus our findings support their eminent role in working memory and show that no functional restoration occurs after neonatal lesions.
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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.
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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.