a b s t r a c tSignificant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal metabotropic glutamate receptor 5 (mGluR5)-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase-3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained effective with chronic administration, although its effects were reversible even when given from birth. The combination of an mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential.

Area prostriata (Pro) has been found to play important roles in the rapid processing of moving stimuli in the far peripheral visual field. However, the specific neural substrates responsible for these functions remain unknown. In this study, we first examined the location, extent, and topography of the rodent equivalent of the primate Pro based on cytoarchitecture and molecular markers. We then identified its intimate connections with the primary visual cortex (V1) using retrograde and anterograde tracers. Our main finding is that medial V1, which receives peripheral visual information, has strong reciprocal connections with the Pro in both rat and mouse while lateral V1 has significantly fewer such connections. The direct V1 inputs to the Pro provide at least one of the shortest pathways for visual information to reach the Pro, and may be crucial to the fast processing of unexpected stimuli in the peripheral visual field.

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Area prostriata is a limbic structure critical to fast processing of moving stimuli in far peripheral visual field. Neural substrates underlying this function remain to be discovered. Using both retrograde and anterograde tracing methods, the present study reveals that the prostriata in rat and mouse receives inputs from multimodal hierarchical cortical areas such as primary, secondary, and association visual and auditory cortices and subcortical regions such as the anterior and midline thalamic nuclei and claustrum. Surprisingly, the prostriata also receives strong afferents directly from the rostral part of the dorsal lateral geniculate nucleus. This shortcut pathway probably serves as one of the shortest circuits for fast processing of the peripheral vision and unconscious blindsight since it bypasses the primary visual cortex. The outputs of the prostriata mainly target the presubiculum (including postsubiculum), pulvinar, ventral lateral geniculate nucleus, lateral dorsal thalamic nucleus, and zona incerta as well as the pontine and pretectal nuclei, most of which are heavily involved in subcortical visuomotor functions. Taken together, these results suggest that the prostriata is poised to quickly receive and analyze peripheral visual and other related information and timely initiates and modulates adaptive visuomotor behaviors, particularly in response to unexpected quickly looming threats.

These results show that MPEP administration could partially rescue the morphological deficits of dendritic spines in Fmr1 KO mice at developmental age.

ObjectiveTo evaluate the potential influence of Foxp3 polymorphism on preeclampsia (PE) susceptibility, we conducted a case-control study in Han Chinese women.Methods Foxp3 genotyping was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 156 PE patients and 252 age-frequency matched controls. Immunohistochemical staining was used to detect the expression of Foxp3 specific transcription factor in 30 PE and 30 normal pregnant women.ResultsThe positive rate of Foxp3 expression in PE (26.67%) was significant difference from that in normal control (63.33%, P<0.05). The frequency of Foxp3-6054 TT genotype was significantly lower in PE patient than that in control. No significant difference was found in Foxp3-3279 genotypes between PE and control, as well as for the variant allele. The frequency of Foxp3-6054A/−3279C haplotype in PE was significantly higher than that in control (P<0.01), while the frequency of Foxp3 6054T/−3279C haplotype was significantly lower in PE patient than that in control (P<0.01).ConclusionOur findings suggest that the immune suppression function in PE patients is weakened, which may result in the occurrence of PE. Foxp3 polymorphism (rs5902434) may be a potential contributor for the development of PE in Han Chinese women.

Area prostriata plays important roles in fast detection and analysis of peripheral visual information. It remains unclear whether the prostriata directly receives and integrates information from other modalities. To gain insight into this issue, we investigated brain-wide afferent projections to mouse prostriata. We find convergent projections to layer 1 of the prostriata from primary and association visual and auditory cortices; retrosplenial, lateral entorhinal, and anterior cingulate cortices; subiculum; presubiculum; and anterior thalamic nuclei. Innervation of layers 2–3 of the prostriata mainly originates from the presubiculum (including postsubiculum) and anterior midline thalamic region. Layer 5 of the prostriata mainly receives its inputs from medial entorhinal, granular retrosplenial, and medial orbitofrontal cortices and anteromedial thalamic nucleus while layer 6 gets its major inputs from ectorhinal, postrhinal, and agranular retrosplenial cortices. The claustrum, locus coeruleus, and basal forebrain provide relatively diffuse innervation to the prostriata. Moreover, Cre-dependent tracing in cortical areas reveals that the cells of origin of the prostriata inputs are located in layers 2–4 and 5 of the neocortical areas, layers 2 and 5 of the medial entorhinal cortex, and layer 5 of the retrosplenial cortex. These results indicate that the prostriata is a unique region where primary and association visual and auditory inputs directly integrate with many limbic inputs.

BackgroundTransforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is scant information on the relation between variations within the TGF-β1 gene polymorphisms and risks of ischemic cerebrovascular diseases. Therefore, this case-controlled study was carried out to investigate the possible association of the TGF-β1 gene C-509T and T869C polymorphisms, and their combined genotypes with the risk of atherosclerotic cerebral infarction (CI) in the Chinese population.ResultsWe recruited 164 CI patients and 167 healthy control subjects who were frequency-matched for age and gender. The frequencies of the -509TT genotype and T allele gene were significantly higher in the CI group (P = 0.007, P = 0.006). The frequencies of +869CC genotype and C allele were higher in the CI group (P = 0.002, P = 0.004). In the CI group, the individuals with -509TT genotype had a significantly higher level of plasma triglyceride (TG) (P = 0.017). +869CC genotype correlated significantly with higher level of plasma low density lipoprotein cholesterol (LDL-c) in the CI group (P = 0.015). With haplotype analysis, the frequency of the -509T/+869C combined genotype was significantly higher in the CI group than in controls (P < 0.001).ConclusionsOur study suggests that C-509T and T869C gene polymorphisms in TGF-β1 may be a critical risk factor of genetic susceptibility to CI in the Chinese population.