Neuroscience
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Deletion of Arrb2 down-regulates autophagy in the mouse hippocampus via Akt-mTOR pathway activation.
The cytoplasmic multifunctional adaptor protein β-arrestin 2 (Arrb2) is involved in the occurrence of various nervous system diseases, such as Alzheimer's disease and Parkinson's disease. Previous laboratory studies have shown that the expression and function of the Arrb2 gene was increased in valproic acid-induced autistic mice models. However, few reports have examined the possible role of Arrb2 in the pathogenesis of autism spectrum disorder. ⋯ Western blot analysis revealed that deletion of Arrb2 caused hyperactivation of Akt-mTOR signaling in the hippocampus. In addition, abnormal mitochondrial dysfunction was observed in Arrb2-/- hippocampal neurons, which was characterized by a reduction in mitochondrial membrane potential and adenosine triphosphate production and an increase in reactive oxygen species levels. Therefore, this study elucidates the interaction between Arrb2 and the Akt-mTOR signaling pathway and provides insights into the role of Arrb2 in hippocampal neuron autophagy.
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Reconsolidation results in the restabilisation, and thus persistence, of a memory made labile by retrieval, and interfering with this process is thought to enable modification or weakening of the original trace. As such, reconsolidation-blockade has been a focus of research aiming to target the maladaptive memories underlying mental health disorders, including post-traumatic stress disorder and drug addiction. Current first-line therapies are not effective for all patients, and a substantial proportion of those for whom therapies are effective later relapse. ⋯ These include factors such as the age and strength of memory, and can broadly be divided into two categories: intrinsic features of the targeted memory itself, and parameters of the reactivation procedure used. With maladaptive memory characteristics inevitably varying amongst individuals, manipulation of the other limitations imposed by procedural variables have been explored to circumvent the boundary conditions on reconsolidation. Although several apparently discrepant results remain to be reconciled and these limitations yet to be truly defined, many studies have produced successful results which encouragingly demonstrate that boundary conditions may be overcome using various proposed strategies to enable translation of a reconsolidation-based intervention to clinical use.
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Predictions of incoming words performed during reading have an impact on how the reader moves their eyes and on the electrical brain potentials. Eye tracking (ET) experiments show that less predictable words are fixated for longer periods of times. Electroencephalography (EEG) experiments show that these words elicit a more negative potential around 400 ms (N400) after the word onset when reading one word at a time (foveated reading). ⋯ Our results show that the N400 potential disappear when the reader recognises the sentence. Furthermore, time-frequency analyses show a larger alpha lateralisation and a beta power increase for memory-encoded sentences. This suggests a more distributed attention and an active maintenance of the cognitive set, in concordance to the predictive coding framework.
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Given the importance of understanding the disorders caused by trans fatty acids (TFAs), this study sought to add different concentrations hydrogenated vegetable fat (HVF) to the diet of Drosophila melanogaster during the developmental period and evaluate the effects on neurobehavioral parameters. Longevity, hatching rate, and behavioral functions were assessed, such as negative geotaxis, forced swimming, light/dark, mating, and aggressiveness. ⋯ As for the biochemical parameters, there was a more significant presence of TFA in flies exposed to HVF at all concentrations evaluated and lower 5HT and DA levels. This study shows that HVF during the developmental phase can cause neurological changes and consequently induce behavioral disorders, thereby highlighting the importance of the type of FA offered in the early stages of life.
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Neonatal pain experiences including traumatic injury influence negatively on development of nociceptive circuits, resulting in persistent pain hypersensitivity in adults. However, the detailed mechanism is not yet well understood. In the present study, to clarify the pathogenesis of orofacial pain hypersensitivity associated with neonatal injury, the involvement of the voltage-gated sodium channel (Nav) 1.8 and the C-C chemokine ligand 2 (CCL2)/C-C chemokine receptor 2 (CCR2) signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined in 190 neonatal facial-injured and sham male rats. ⋯ Blockages of Nav1.8 in the incised region and CCR2 in the TG suppressed the enhancement of mechanical hypersensitivity in the Incision-Incision group. Administration of CCL2 into the TG enhanced mechanical hypersensitivity in the Sham-Sham, Incision-Sham and Sham-Incision group. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Nav1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.