Sonhar para esquecer: uma introdução à hipótese da Aprendizagem-Reversa / Dream to forget: an introduction to the Reverse-Learning hypothesis

As ferramentas e aportes conceituais da neurociência têm produzido avanços nas pesquisas sobre as características do sono e dos sonhos, associando estas aos processos de consolidação de memória. O presente artigo visa analisar a contribuição da hipótese da “Aprendizagem-Reversa” ao campo da psicologia. Pela natureza associativa da memória e pelo fato de forjarem-se novas conexões neurais diariamente através do aprendizado, as redes neuronais criariam memórias “falsas”. Com o risco de ficar sobrecarregada, esta rede passaria por uma “desaprendizagem” periódica; seria necessário um mecanismo para enfraquecer as conexões sinápticas errôneas durante o sono REM. As implicações dessa teoria serão avaliadas, que vão desde como evoluiu o sistema nervoso até a desconsideração de que os sonhos tenham origem nas necessidades psicológicas individuais.

Brucine chitosan thermosensitive hydrogel for intra-articular injection / 药学学报

The aim of this study was to develop a sustained release converse thermosensitive hydrogel for intra-articular injection using chitosan-glycerol-borax as matrix, its physical properties and biocompatibility were investigated. Taking gelation time and gelation condition as index, the influence of concentration of chitosan, ratio of chitosan to glycerol, pH on physical properties of hydrogel were investigated. And then the in vitro drug release, rheological properties and biocompatibility were studied. The thermosensitive hydrogel flows easily at room temperature and turns to gelation at body temperature, which can certainly prolong the release of drug and has good biocompatibility.

Mechanism of Neuronal Damage in Epilepsy

Epilepsy is one of the most common episodic neurological diseases, and patients with epilepsy may experience a range of neurological, psychological, and behavioral problems. Recurring seizures potentially contribute to the progressive severity of epilepsy, cognitive and behavioral consequences. The clinical and experimental evidences involving radiological, pathological, and biochemical studies suggest that seizures can potentially injure the brain via a number of diverse molecular, cellular, and network mechanisms. The damage includes neuronal death, axodendritic changes, molecular changes of synaptic membrane, and gliosis and increased neurogenesis. Those changes induce rewiring of the network and reorganization of synapses, causing alteration of the functional and morphological properties as the mechanism of epilepsy. As the most overt form of alterations, the neuronal death may result from the execution of cellular programs that are similar to the molecular machinery of programmed cell death including the caspases and bcl-2 family proteins. In epileptic seizure, the neurons are overexcited and run out of energy. The low energy state is closely related with the necrotic pathway. The features suggest that the neuronal death in epilepsy may follow characteristic mechanism, suggesting necrotic programmed cell death pathway. Therapeutic modification of seizure-induced death could open new strategy in epilepsy treatment.

Phosphorylation of 46-kappa Da protein of synaptic vesicle membranes is stimulated by GTP and Ca2+/calmodulin

The release of neurotransmitter is regulated in the processes of membrane docking and membrane fusion between synaptic vesicles and presynaptic plasma membranes. Synaptic vesicles contain a diverse set of proteins that participate in these processes. Small GTP-binding proteins exist in the synaptic vesicles and are suggested to play roles for the regulation of neurotransmitter release. We have examined a possible role of GTP-binding proteins in the regulation of protein phosphorylation in the synaptic vesicles. GTPgammaS stimulated the phosphorylation of 46 kappa Da protein (p46) with pI value of 5.0-5.2, but GDPbetaS did not. The p46 was identified as protein interacting with C-kinase 1 (PICK-1) by MALDI-TOF mass spectroscopy analysis, and anti-PICK-1 antibody recognized the p46 spot on 2-dimensional gel electrophoresis. Rab guanine nucleotide dissociation inhibitor (RabGDI), which dissociates Rab proteins from SVs, did not affect phosphorylation of p46. Ca2+/ calmodulin (CaM), which causes the small GTP- binding proteins like Rab3A and RalA to dissociate from the membranes and stimulates CaM- dependnet protein kinase(s) and phosphatase, strongly stimulate the phosphorylation of p46 in the presence of cyclosporin A and cyclophylin. However, RhoGDI, which dissociates Rho proteins from membranes, reduced the phosphorylation of p46 to the extent of about 50%. These results support that p46 was PICK-1, and its phosphorylation was stimulated by GTP and Ca2+/CaM directly or indirectly through GTP-binding protein(s) and Ca2+/CaM effector protein(s). The phosphorylation of p46 (PICK-1) by GTP and Ca2+/CaM may be important for the regulation of transporters and neurosecretion.

Antagonistic effect of aqueous extract of detoxified cottonseeds on corticosterone-induced lesion in cultured PC12 cells / 中国中药杂志

<p><b>OBJECTIVE</b>To study the possible mechanism of aqueous extract of detoxified cottonseeds (CTN-W).</p><p><b>METHOD AND RESULT</b>CTN-W 0.01, 0.03, 0.10, 0.30 mg.mL-1 was incubated directly with the synaptic membrane extracted from the cerebral cortex in rats, and adenylyl cyclase (AC) activity was detected by using radio-immunoassay.</p><p><b>RESULT</b>Showed that CTN-W could activate AC in a dose-dependend manner. After incubation with PC12 cells in the presence of corticosterone 2 x 10(-4)mol.L-1 for 48 h, CTN-W 0.08, 0.4, 2 mg.mL-1 protected PC12 cells from the lesion induced by corticosterone.</p><p><b>CONCLUSION</b>Antidepressant and anxiolytic effects of CTN-W are related with the activation of AC-cAMP pathway in signal transduction system, thus protecting neurons from the lesion. These two aspects maybe partly form the mechanism of CTN-W's action.</p>

In vivo and in vitro effect of imipramine and fluoxetine on Na+, K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10 percent) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27 percent) in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80 percent) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients

The proteins of synaptic vesicle membranes are affected during ageing of rat brain

Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions, i.e. the regulation of cytoskeletal organization in response to extracelluar growth factors and in dendritic neuron development. In this study, we have examined the regulation of small GTP-binding proteins that are implicated in neurosecretion and differentiation of neuron during ageing processes. Comparison of small GTP-binding proteins from the synaptosome and crude synaptic vesicles (LP2 membranes) of 2 months and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain. The dissociation of Rab3A by Ca2+/calmodulin (CaM) from SV membranes was not changed during aging. Ca2+/CaM stimulated phosphorylation of the 22 and 55-kDa proteins in SV membranes from the aged rat brain, and inhibited phosporylation of 30-kDa proteins. GTPgammaS inhibited phosphorylation of the 100-kDa proteins and stimulated phosphorylation of the 70 kDa in LP2 membranes from both the young and aged rat brains, whereas GDPbetaS caused just the opposite reaction. These results suggest that protein phosphorylation and regulation of Rho family GTPases in rat brain appears to be altered during ageing processes.

The proteins of synaptic vesicle membranes are affected during ageing of rat brain

Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions, i.e. the regulation of cytoskeletal organization in response to extracelluar growth factors and in dendritic neuron development. In this study, we have examined the regulation of small GTP-binding proteins that are implicated in neurosecretion and differentiation of neuron during ageing processes. Comparison of small GTP-binding proteins from the synaptosome and crude synaptic vesicles (LP2 membranes) of 2 months and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain. The dissociation of Rab3A by Ca2+/calmodulin (CaM) from SV membranes was not changed during aging. Ca2+/CaM stimulated phosphorylation of the 22 and 55-kDa proteins in SV membranes from the aged rat brain, and inhibited phosporylation of 30-kDa proteins. GTPgammaS inhibited phosphorylation of the 100-kDa proteins and stimulated phosphorylation of the 70 kDa in LP2 membranes from both the young and aged rat brains, whereas GDPbetaS caused just the opposite reaction. These results suggest that protein phosphorylation and regulation of Rho family GTPases in rat brain appears to be altered during ageing processes.

Effects of w3/ w6 fatty acids on behavioral developments of rats: Relation with neurotransmitters

Docosahexaenoic acid(DHA) is a major fatty acid of the gray matter in brain, especially of the synaptic membranes. Modification of membrane fatty acids by dietary fatty acids may influence membrane characteristics and metabolism of neurotransmitters including it's release and reuptake. The effect of w3/w6 fatty acids in maternal diet on the brain neurotransmitters of the offsptings and their behavioral development were investigated in this study. Adult female rats were fed experimental diets with different contents of w3 and w6 fatty acids throughtout pregnancy and lactation and up to 16weekss of pup's age. Experimental diets consisted of 10 wt% fat: cornoil (CO: source of w6, LA), perilla oil (PO: source of w3, a-LNA) and fish oil(FO: source of lonfg chain w3, EPA & DHA). At 3,7 and 16weeks of age, frontal cortex, corpus striatum, thaltmus and cerebellum were dissected out of the whole brain, and the concentrations of 5-hydroxytryptamines(5-HT), catechoamines,and their metabolites were measured by HPLC-ECD. At 16weeks of age, fatty acid compositions of whole brain were determined by GLC. Physical development test in Y-water maze were performed at 15weeks of pup's age. The concentrations of 5-HT in thalamus & hypothalamus was found to be most significiantly correlated with learning ability(r=0.508, p<0.05). At 15weeks of age, the PO group showed higher learning ability compared to the CO or the FO group. Evemn though the DHA level stays rather constant in thhe brain tissue, the ratios of arachidoni c acid(AA,w6)/EPA+DHA(w3) vary significiantly with dietary fatty acids. DHA is known to fulfill very important structural and/or metabolic funtion in membrane system of the brain and AA and its metabolites may also act as transsynaptic messenger and/or second messenger and as the substrate for the production of many biologically active compounds, such as prostaglandins. Therefore, to accomplish full development of brain, proper supply of AA as well as DHA must be considered. Much more studies are needed to clarify th.

(3H)MK-801 binding to the synaptic membranes of rat forebrains: Age-related regulation by glutamate, glycine and spermine

The N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission is involved in synaptic plasticity, developmental processes, learning and memory and many neuropathological disorders including age-related diseases. In the present study, regulation of the NMDA receptor properties by various ligands was investigated using (3H)MK-801 binding studies in the synaptic membranes of young and aged rat forebrains. The binding in the presence of glutamate and glycine increased dramatically with growth between 1 and 6 weeks old, and thereafter declined gradually with aging. Glutamate, glycine or spermine respectively increased the binding with growth. Glutamate maintained the binding during aging, while glycine or spermine significantly decreased the binding in the aged brain. The maximum stimulation by glycine varied depending on the ages of brains. Greater sensitivity to glycine was observed at 1 week and 3 months and the sensitivity was significantly reduced in the aged brain. In contrast, spermine showed similar stimulation patterns in young and aged rats. These results indicated that the functional properties of the NMDA receptor-ion channel complex in young and aged rat forebrains are differentially regulated by agonists, and the reduction of the receptor function with normal aging may be, in some degree, due to the reduction of the receptor sensitivity to glycine.