Neuroscience
-
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by impaired social communication, abnormal repetitive behaviors and restricted interests and/or sensory behaviors. It has been widely accepted that ASD involves a complex interplay of both genetic and environmental risk factors. Existing medications are only symptomatic treatments, there are no effective treatments that can improve these core social behavior deficits. ⋯ BTBR mice were treated either with Epothilone D dissolved in 99% dimethyl sulfoxide (DMSO) or with 99% DMSO vehicle. Our studies demonstrated that the restricted and repetitive behaviors of BTBR mice were improved after Epothilone D treatment, which could be achieved by improving microtubule stability and further regulating the expression of excitatory synapse-related and myelin-related proteins. These results indicate that microtubule stability may be a new and promising therapeutic target for treating patients with ASD.
-
Parkinson's disease (PD) is one of the most common chronic progressive neurodegenerative diseases that affects both motor and non-motor functions. Bile acids modulate the immune system by targeting brain receptors. INT-777, a 6α-ethyl-23(S)-methyl derivative of cholic acid (S-EMCA), acts as an agonist for Takeda G protein-coupled receptor-5 (TGR5) and has neuroprotective properties. ⋯ However, TGR5 knockdown in microglia abolished INT-777's inhibition of TNF-α release, resulting in neuronal death. Therefore, PD cognitive impairment is associated with hippocampal TNF-α elevation as a result of mitochondrial damage in microglia. Our data reveal the potential role of TGR5 in modulating inflammation-mediated neurodegeneration in PD, and provides new insights for bile acid metabolites as promising disease-modifying drugs for PD.
-
Exercise duration differentially effects age-related neuroinflammation and hippocampal neurogenesis.
The physiological effects of exercise vary as a function of frequency and length. However, research on the duration-dependent effects of exercise has focused primarily on young adults and less is known about the influence of exercise duration in the aged. The current study compared the effects of short-term and long-term running wheel access on hippocampal neurogenesis and neuroimmune markers in aged (19-23 months) male C57BL/6J mice. ⋯ While in contrast brain levels of IL-6 were reduced by both short- and long-term exercise. Additional findings showed that exercise does not modulate all aspects of age-related neuroinflammation and/or may have differential effects in hippocampal compared to brain samples. Overall, the data indicate that increasing exercise duration produces more robust effects on immune modulation and hippocampal neurogenesis.
-
Evidence has shown that circ_0000518 is upregulated in peripheral of multiple sclerosis (MS) patients, suggesting that it may play an important role in the progression of MS. However, its specific mechanism in MS progression is unclear. In this study, the human microglial clone 3 (HMC3) cells were treated with 100 ng/mL of LPS for 24 h, then the short hairpin RNA against hsa_circ_0000518 (sh-hsa_circ_0000518) was transfected into cells and incubated for 48 h. ⋯ Mechanistic studies revealed that interfering with FUS promoted the polarization of HMC3 cells from the M1 phenotype to the M2 phenotype via activation of CaMKKβ/AMPK-PGC-1α pathway, whereas this promoting effect was counteracted by STO-609. In an experimental autoimmune encephalomyelitis (EAE) mouse model, we observed that circ_0000518 knockdown reduced circ_0000518 and FUS expression in brain and spinal cord tissues, reduced neurological scores in mice, and alleviated inflammatory cell infiltration in the CNS. Summarily, our study identified that circ_0000518 promotes macrophage/microglial M1 polarization through the FUS/CaMKKβ/AMPK pathway and aggravates MS.
-
Review Meta Analysis
Bilateral intraparietal activation for number tasks in studies using an adaptation paradigm: A meta-analysis.
Mathematical processing is important for professional success. The adaptation paradigm has been widely used to study the brain underpinnings of mathematical processing. In this study, we aim at shedding light on an important component of mathematical processing, namely numerical cognition. ⋯ We found a bilateral Intraparietal Sulcus (IPS) activation in studies using both symbolic and non-symbolic stimuli formats. We also found a right lateralized brain activation for the non-symbolic condition and a left lateralized brain activation for the symbolic condition. These results imply that the adaptation paradigm likely targets numeric magnitude processing and confirms the potency of this paradigm to activate the IPS.