Brain research
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The roles of spinal N-methyl-d-aspartic acid receptor 2B (NR2B) subunit in central sensitization of chronic visceral pain were investigated. A rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD) on post-natal days 8-14. Responses of the external oblique muscle of the abdomen to CRD were measured to evaluate the sensitivity of visceral pain in rats. ⋯ Spinal administration of genistein, a specific inhibitor of tyrosine kinases, also decreased the visceral pain hypersensitivity of IBS-like rats in a dose-dependent manner. In addition, the expression of phosphorylated NR2B subunit was decreased after spinal administration of Ro 25-6981 or genistein in IBS-like rats. In conclusion, tyrosine kinase activation-induced phosphorylation of NR2B subunit may play a crucial role in central sensitization of chronic visceral pain.
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The brain is treated as a nested hierarchical complex system with substantial interactions across spatial scales. Local networks are pictured as embedded within global fields of synaptic action and action potentials. Global fields may act top-down on multiple networks, acting to bind remote networks. ⋯ The resulting models are transparently related to several EEG and steady state visually evoked potentials correlated with cognitive states, including estimates of neocortical coherence structure, traveling waves, and standing waves. The global models suggest that global oscillatory behavior of self-sustained (limit-cycle) modes lower than about 20 Hz may easily occur in neocortical/white matter systems provided: Background cortical excitability is sufficiently high; the strength of long cortico-cortical axon systems is sufficiently high; and the bottom-up influence of local networks on the global dynamic field is sufficiently weak. The global models provide “entry points” to more detailed studies of global top-down influences, including binding of weakly connected networks, modulation of gamma oscillations by theta or alpha rhythms, and the effects of white matter deficits.
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Apolipoprotein E (ApoE) is found in three different forms in humans (ApoE2, ApoE3 and ApoE4), and ApoE polymorphism is recognized as a major risk factor for Alzheimer's disease (AD). ApoE is involved in lipid and cholesterol transport, cell repair, and amyloid-β deposition and certain studies suggest potential implications in neurogenesis. In this regard, we investigated the possible impact of the three different human ApoE isoforms on neurogenesis. ⋯ Our study highlights the role of ApoE in neurogenesis, and shows for the first time an early inequality between the ApoE genotypes. The reduced neurogenesis observed for the ApoE4 genotype and the improved results obtained in young ApoE2 females support the idea of a difference in the balance between neuronal birth and death modulated by the ApoE polymorphism in young animals. The maintenance of this balance and its modulation can influence pathophysiological mechanisms predisposing to neurodegenerative diseases like AD.
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The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. ⋯ Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.
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Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain. ⋯ Radioactive in situ hybridization was performed to determine endogenous PRCP mRNA expression. In addition, using a gene-trap mouse model for PRCP deletion, X-gal staining was performed to further determine PRCP distribution. Results from both approaches showed that PRCP gene is broadly expressed in the brain.