Neuroscience
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Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. ⋯ The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.
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Recessive mutations in GRXCR2 cause deafness in both humans and mice. In Grxcr2 null hair cells, the sensory receptors for sound in the inner ear, stereocilia are disorganized. Reducing the expression of taperin, a protein that interacts with GRXCR2 at the base of stereocilia, corrects the morphological defects of stereocilia and restores hearing in Grxcr2 null mice. ⋯ Then Grxcr2 null mice were crossed with one of these taperin mutant mice. The following morphological analysis revealed that reducing taperin expression indeed corrected stereocilia morphological abnormalities in Grxcr2 null mice. Functional analysis further confirmed that reducing taperin expression partially restored hearing in Grxcr2 null mice.
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Diffusion Tensor Imaging (DTI) and Manganese Enhanced MRI (MEMRI) are noninvasive tools to characterize neural fiber microstructure and axonal transport. A combination of both may provide novel insights into the progress of neurodegeneration. To investigate the relationship of DTI and MEMRI in white matter of tauopathy, twelve optic nerves of 11-month-old p301L tau mice were imaged and finished with postmortem immunohistochemistry. ⋯ Immunohistochemistry findings showed that ONAR, mD, and rD are significantly correlated with the myelin content (Myelin Basic Protein, p < 0.05) but not with the axonal density (SMI-31), tubulin density, or tau aggregates (AT8 staining). In summary, slower axonal transport appeared to have less myelinated axons and thinner remaining axons, associated with reduced rD and mD of in vivo DTI. A combination of in vivo MEMRI and DTI can provide critical information to delineate the progress of white matter deficits in neurodegenerative diseases.
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Although the exact etiology of Parkinson's disease (PD) is still unknown, there are a variety of treatments available to alleviate its symptoms according to the development stage of PD. Deep brain stimulation (DBS), the most common surgical treatment for advanced PD, accurately locates and implants stimulating electrodes at specific targets in the brain to deliver high-frequency electrical stimulation that alters the excitability of the corresponding nuclei. However, for different patients and stages of PD development, there exists a choice of the optimal DBS protocol. ⋯ Lastly, the evolution of the network state from normal to pathological is simulated. The critical point of network state transitions is determined. These results provide a quantitative and qualitative method for determining the optimal regimen for DBS for PD, which is helpful for clinical practice.
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Cellular senescence is an important contributor to aging and age-related diseases such as Alzheimer's disease (AD). Senescent cells are characterized by a durable cell proliferation arrest and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP), which participates in the progression of neurodegenerative disorders. Clearance of senescent glial cells in an AD mouse model prevented cognitive decline suggesting pharmacological agents targeting cellular senescence might provide novel therapeutic approaches for AD. Δ133p53α, a natural protein isoform of p53, was previously shown to be a negative regulator of cellular senescence in primary human astrocytes, with clinical implications from its diminished expression in brain tissues from AD patients. ⋯ Our data suggest that Aβ-induced astrocyte cellular senescence is associated with accelerated DNA damage, and upregulation of full-length p53 and its senescence-inducing target gene p21WAF1. We also show that exogenously enhanced expression of Δ133p53α rescues human astrocytes from Aβ-induced cellular senescence and SASP through both protection from DNA damage and dominant-negative inhibition of full-length p53, leading to inhibition of Aβ-induced, astrocyte-mediated neurotoxicity. The results presented here demonstrate that Δ133p53α manipulation could modulate cellular senescence in the context of AD, possibly opening new therapeutic avenues.