Neuroscience
-
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.
-
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.
-
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.
-
The regulation of D₃ receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D₃-preferring radioligand [(3)H]WC-10 and a D₂-preferring radioligand [(3)H]raclopride were used and the absolute densities of the dopamine D₃ and D₂ receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from five cases of DLBD, which included dementia with Lewy bodies (DLB, n=4) and Parkinson disease dementia (PDD, n=1). The densities of the dopamine D₁ receptor, vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. ⋯ VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however, the significant reduction was found in the putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D₃ receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric states such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations.
-
Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception. In the present study, we explored the interaction between the two systems by examining the mutual effects between TNF-α and the Ang II/AT1 receptor axis in dorsal root ganglion (DRG) neurons. Rat DRG neurons were treated with TNF-α in different concentrations for different lengths of time in the presence or absence of transcription inhibitor actinomycin D, TNF receptor 1 (TNFR1) inhibitor SPD304, β-catenin signaling inhibitor CCT031374, or different kinase inhibitors. ⋯ In conclusion, we demonstrate that TNF-α inhibits AT1 receptor expression at the transcription level via TNFR1 in rat DRG neurons by increasing the soluble β-catenin level through the p38 MAPK/GSK-3β pathway. In addition, Ang II appears to inhibit and induce TNF-α expression via the AT1 receptor and the AT2 receptor in DRG neurons, respectively. This is the first evidence of crosstalk between TNF-α and the Ang II/AT receptor axis in DRG neurons.