Neuroscience
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The hippocampus, derived from medial regions of the telencephalon, constitutes a remarkable brain structure. It is part of the limbic system, and it plays important roles in information encoding, related to short-term and long-term memory, and spatial navigation. It has also attracted the attention of many clinicians and neuroscientists for its involvement in a wide spectrum of pathological conditions, including epilepsy, intellectual disability, Alzheimer disease and others. ⋯ As well as original landmark findings, modern techniques such as large-scale in situ hybridizations, in utero electroporation and the study of mouse mutants with hippocampal phenotypes, add further detail to our knowledge of the finely regulated processes which form this intricate structure. Molecular signatures are being revealed related to field, intra-field and laminar cell identity, as well as, cell compartments expressing surface proteins instrumental for connectivity. We summarize here old and new findings, and highlight elegant tools used to fine-study hippocampal development.
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A number of psychiatric illnesses have been associated with prenatal disturbance of brain development, including autism, attention deficit hyperactivity disorder, and schizophrenia. Individuals afflicted with these disorders exhibit both repetitive motor and cognitive behavior. The potential role that environmental insult to the developing brain may play in generating these aberrant behaviors is unclear. ⋯ Perseverative errors and non-perseverative errors were recorded in early stages of the testing, at the 0 delay interval. While performing DA, FIMs made more errors of perseveration than CONs yet the number of total errors committed did not differ between groups. The presence of motor stereotypies and cognitive perseveration in fetally irradiated non-human primates suggests that environmental insult to the embryonic brain may contribute to repetitive motor and cognitive behaviors in neuropsychiatric diseases.
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The abilities of docosahexaenoic acid (DHA) and exercise to counteract cognitive decay after traumatic brain injury (TBI) is getting increasing recognition; however, the possibility that these actions can be complementary remains just as an intriguing possibility. Here we have examined the likelihood that the combination of diet and exercise has the added potential to facilitate functional recovery following TBI. Rats received mild fluid percussion injury (mFPI) or sham injury and then were maintained on a diet high in DHA (1.2% DHA) with or without voluntary exercise for 12days. ⋯ These effects of FPI were optimally counteracted by the combination of DHA and exercise. Our results support the possibility that the complementary action of exercise is exerted on restoring membrane homeostasis after TBI, which is necessary for supporting synaptic plasticity and cognition. It is our contention that strategies that take advantage of the combined applications of diet and exercise may have additional effects to the injured brain.
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Nuclear factor (NF)-κB acetylation has been shown to participate in a number of neurological processes by regulating the expression of certain genes. We have previously demonstrated the neuronal nitric oxide synthase (nNOS) expression and nitric oxide (NO) production may be regulated by NF-κB acetylation via an NF-κB responsive element within the nNOS promoter in neuronal cells. p300 is a ubiquitous transcription coactivator with intrinsic histone acetyltransferase (HAT) activity, which is important in the nervous system. ⋯ Meanwhile, p300 was shown to directly acetylate NF-κB p65 and p50 subunits, interact with NF-κB and bind to the NF-κB responsive element region within the nNOS promoter. Taken together, our results indicate p300 acts as both an HAT and a coactivator in regulating NF-κB-mediated nNOS expression, which provide some correlations between p300 and nNOS in neuronal cell, and suggest that some p300-related neurological disorders may be partially based on its effect on the nNOS expression.
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Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). ⋯ Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.