Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

AIMTo investigate the protective role of HO/CO systems in IL-1beta induced islest apoptosis and to explore the mechanisms of the protective effect of fructose-1, 6-disphosphate (FDP).

METHODSThe pancreases of the rats were removed to collect islets cells. The cells were incubated with IL-1beta with/or FDP. Cell activity, insulin secretion, HO-1 activity, CO content and apoptotic percentage were detected.

RESULTSHO-1 activity and CO content of the normal control group were low. IL-1beta induced a significant decrease of cell activity and insulin release, flow cytometry analysis showed that apoptotic percentage of islet cells remarkably increased following the addition of IL-1beta, FDP obviously improved the islets cellular activity damaged by IL-1beta, and basic amount of insulin secretion and stimulated by high glucose were improved (P < 0.01). Content of CO and activity of HO-1 were higher in the IL-1beta group than the normal control group (P < 0.05), and there were significant differences between the FDP groups and IL-1beta group. FDP decreased cell apoptotic percentage. Activities of HO-1 and content of CO were higher than that in the IL-1beta group (P < 0.01).

CONCLUSIONFDP can attenuate the IL-1beta induced apoptosis of cultured beta cells, the mechanism of which may be improved HO-1 activity and CO content.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Carbon Monoxide ; metabolism ; Cells, Cultured ; Female ; Fructosediphosphates ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; physiology ; Insulin ; secretion ; Interleukin-1beta ; antagonists & inhibitors ; pharmacology ; Islets of Langerhans ; cytology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the epidemiology and etiologic characteristics of a Dengue fever outbreak in Fuzhou from the beginning of September to the end of October in 2004 in order to understand the source of infection.

METHODSData on descriptive epidemiology was collected to study the characteristics and related factors to the epidemic. Dengue virus was isolated through the use of C6/36 cell line while viral serotypes were identified by indirect immunofluorecent assay with type-specific monoclonal antibody. The sources of infection were traced by nucleotide sequencing.

RESULTSDuring the epidemic, 93 cases occured consistently with the region entomoplily growth and decay. The viruses of 6 strains isolated from 10 patients' blood specimens were identified as dengue virus type 1. Phylogenetic evidence suggested that the viral isolate had high genetic relation with the isolates from Kampuchea (DENV-1/KHM/2001; GenBank Accession No. L0904278).

CONCLUSIONThe epidemic was caused by introduction of patients migrating into Fuzhou.

China ; epidemiology ; Dengue ; epidemiology ; Dengue Virus ; genetics ; isolation & purification ; Disease Outbreaks ; Emigration and Immigration ; Genetic Variation ; Humans ; Phylogeny

Objective To investigate spatial and temporal patterns of event-related potentials (ERP) evoked by facial expression.Methods ERP was recorded in 25 healthy subjects while they performed facial recognition task. Repeated-measure one-way ANOVA was adopted to compare the subjects' responses to stimulation by 3 different expressions (positive, neutral and negative) with statistical parametric mapping (SPM). Results Significant facial expression effects occurred separately in the left parietal and bilateral occipital regions (280-340 ms), left frontal region (400-420 ms), and right prefrontal region (480-500 ms).In 4 time periods, significant difference was observed between positive and neutral emotion wave in the right frontoparietotemporal and left prefrontal regions (60-80 ms), right occipital region (120-140 ms), left occipital region (280-320 ms), and left frontoparietal region (400-440 ms). Significant difference between negative and neutral emotion waves was observed in 5 time periods in the right occipital region (120-140 ms), central frontoparietal region (220-240 ms), central parietal region (280-300 ms),left parietal and right temporopartial regions (320-340 ms) and frontopartial occipitotemporal region (480-500 ms).Conclusions The spatiotemporal patterns of ERP suggest that the information processing of facial expression involves extensive brain regions dynamically.

Objective To investigate spatial and temporal patterns of event-related potentials (ERP) evoked by facial expression.Methods ERP was recorded in 25 healthy subjects while they performed facial recognition task. Repeated-measure one-way ANOVA was adopted to compare the subjects' responses to stimulation by 3 different expressions (positive, neutral and negative) with statistical parametric mapping (SPM). Results Significant facial expression effects occurred separately in the left parietal and bilateral occipital regions (280-340 ms), left frontal region (400-420 ms), and right prefrontal region (480-500 ms).In 4 time periods, significant difference was observed between positive and neutral emotion wave in the right frontoparietotemporal and left prefrontal regions (60-80 ms), right occipital region (120-140 ms), left occipital region (280-320 ms), and left frontoparietal region (400-440 ms). Significant difference between negative and neutral emotion waves was observed in 5 time periods in the right occipital region (120-140 ms), central frontoparietal region (220-240 ms), central parietal region (280-300 ms),left parietal and right temporopartial regions (320-340 ms) and frontopartial occipitotemporal region (480-500 ms).Conclusions The spatiotemporal patterns of ERP suggest that the information processing of facial expression involves extensive brain regions dynamically.