Neuroscience
-
Comparative Study
Distinct effects of sonic hedgehog and Wnt-7a on differentiation of neonatal neural stem/progenitor cells in vitro.
Sonic hedgehog (Shh) and Wnt-7a are morphogens involved in embryonic as well as ongoing adult neurogenesis. Their effects on the differentiation and membrane properties of neonatal neural stem/progenitor cells (NS/PCs) were studied in vitro using NS/PCs transduced with either Shh or Wnt-7a. Eight days after the onset of in vitro differentiation the cells were analyzed for the expression of neuronal and glial markers using immunocytochemical and Western blot analysis, and their membrane properties were characterized using the patch-clamp technique. ⋯ The electrophysiological analysis revealed that Wnt-7a increased, while Shh decreased the incidence of cells displaying a neuron-like current pattern, represented by outwardly rectifying K(+) currents and tetrodotoxin-sensitive Na(+) currents. Additionally, Wnt-7a increased cell proliferation only at the early stages of differentiation, while Shh promoted proliferation within the entire course of differentiation. Thus we can conclude that Shh and Wnt-7a interfere differently with the process of neuronal differentiation and that they promote distinct stages of neuronal differentiation in neonatal NS/PCs.
-
A significant number of postmenopausal women report increased anxiety and vulnerability to stress, which has been linked to decreased secretion of ovarian steroids. Communication between the serotonin system and the corticotropin releasing factor (CRF) system determines stress sensitivity or resilience. This study examines the effects of the ovarian steroids, estradiol (E) and progesterone (P) on the CRF system components that impact serotonin neurons in the midbrain of nonhuman primates. ⋯ E±P increased UCN1 immunostaining in the cell bodies and increased UCN1 fiber density in the caudal linear nucleus. Estrogen receptor beta (ERβ), but not ERα was detected in the nucleus of UCN1-positive neurons. While the mechanism of ovarian hormone regulation of the midbrain CRF system requires further investigation, these studies clearly demonstrate another pathway by which ovarian hormones may have positive effects on anxiety and mood regulation.
-
Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated. In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. ⋯ All of these GABA-mediated actions were found to occur in histochemically-identified cholinergic neurons. Taken together, these data indicate for the first time that cholinergic neurons of the LDT exhibit functional GABA(A, B and C) receptors, including extrasynaptically located GABA(A) receptors, which may be tonically activated by synaptic overflow of GABA. Accordingly, the activity of cholinergic LDT neurons is likely to be significantly affected by GABAergic tone within the nucleus, and so, demonstrated effects of GABA on behavioral state may be mediated, in part, via direct actions on cholinergic neurons in the LDT.
-
Adolescence represents a time of significant cortical restructuring. Current theories posit that during this period connections between frequently utilized neural networks are strengthened while underutilized synaptic connections are discarded. The aim of the present study was to examine the developmental evolution of connectivity between brain regions using the sleep EEG. ⋯ No age-related trend was found in interhemispheric coherence. Our results indicate that sleep EEG coherence increases with age and that these increases are confined to specific brain regions. This analysis highlights the utility of the sleep EEG to measure developmental changes in brain maturation.
-
For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. ⋯ These results suggest that cancer cells and their associated stromal cells release nerve growth factor (NGF), which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving cancer pain. Similar to therapies that target the cancer itself, the data presented here suggest that, the earlier therapies blocking this pathological nerve remodeling are initiated, the more effective the control of cancer pain.