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ABSTRACT: The treatment of Alzheimer's disease (AD) has been hampered by a lack of sensitive and specific non-invasive diagnostic methods. Quantum dots (QD) are nano-crystals with unique photo-physical properties that bypass some of the limitations of conventional dyes and imaging tools. This study is aimed to evaluate the fluorescence properties of a QD probe conjugated with an anti-Aβ antibody (QD-Aβ-Ab). Healthy mice and mice bearing mutated human APP695swe and APP717 V-F transgenes received intracerebroventricular injection of the probe for subsequent imaging. Immunohistochemistry revealed that Aβ1-42 was distributed in the hippocampus CA1 area in the APP transgenic mice. Fluorescence microscopy demonstrated that fluorescence was mainly observed in the hippocampus area, the cerebral cortex, sagittal septum and striatum of APP transgenic mice. In vivo imaging of mice receiving the QD-Aβ-Ab probe showed that healthy mice exhibited a narrow range of fluorescence and lower fluorescence intensity compared with APP transgenic mice. The mean fluorescence intensity of brain tissues of healthy C57BL mice was 12.3784 ± 3.9826, which was significantly lower than that of 10- and 16-month-old APP transgenic mice (45.03 ± 2.66 and 46.69 ± 3.22, respectively; P < 0.05). In this study we present the first direct evidence that QD-Aβ-Ab conjugate probes can track in vivo state of Aβ accumulation in mice and the findings suggest that such probes may be of potential use for early molecular diagnostic imaging of AD.
Cellular and Molecular Neurobiology 05/2013; · 1.97 Impact Factor
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ABSTRACT: Hirayama disease is characterized by asymmetrical focal weakness and atrophy of the distal upper limbs with onset in the teens and early 20s. This retrospective study aims to review clinical features of the children (onset before the age of 18 years) with Hirayama disease from mainland of China. Sixty-five children who fulfilled the clinical criteria for Hirayama disease were enrolled. The mean age of onset was 15.7 years, 3.3 years later than the peak age for the normal growth curve. Electrophysiology studies showed chronic denervation changes in C7-T1 segments with normal sensory nerve conduction. Flexion cervical magnetic resonance imaging (MRI) showed forward shifting of the posterior dural sac and engorgement of the posterior epidural venous plexus. Therapeutic intervention with cervical collar can induce a premature arrest of disease progression. Knowledge and awareness of Hirayama disease will facilitate diagnosis and therapeutic intervention in its early stages.
Journal of child neurology 04/2013; · 1.59 Impact Factor
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ABSTRACT: Previous studies have suggested that macrophage migration inhibitory factor (MIF) may play a critical role in the pathogenesis of Guillain-Barre syndrome (GBS); however, its definite mechanism remains unknown. In this study, we prepared the monocytes from the peripheral blood mononuclear cells (PBMCs) of GBS patients and the controls. Lipo-oligosaccharide (LOS) from Campylobacter jejuni was used as the stimulus of the monocytes in vitro and siRNA-MIF was used to explore the roles of MIF in LOS-induced response. Significantly, silencing of MIF attenuated the LOS-induced up-regulation of Toll-like receptor 4 (TLR4) and translocation of NF-кB into the nucleus; we also observed the up-regulation of IL-12p40, TNF-α, IL-6, CXCL8 and CCL5 in GBS monocytes with LOS stimulus; and siRNA-MIF overrided the effects of LOS on the production of the TNF-α, IL-6, and CXCL8. Conclusively, our study provides evidences that MIF may participate in the pathogenesis of GBS by modulating the LOS-induced response through TLR4 signaling pathway.
Journal of neuroimmunology 02/2013; · 2.84 Impact Factor
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ABSTRACT: The catalytic steam gasification of pig compost (PC) for hydrogen-rich gas production was experimentally investigated in a fixed bed reactor using the developed NiO on modified dolomite (NiO/MD) catalyst. A series of experiments have been performed to explore the effects of catalyst, catalytic temperature, steam to PC ratio and PC particle size on the gas quality and yield. The results indicate that the NiO/MD catalyst could significantly eliminate the tar in the gas production and increase the hydrogen yield, and the catalyst lives a long lifetime in the PC steam gasification. Moreover, the higher catalytic temperature and smaller PC particle size can contribute to more hydrogen production and gas yield. Meanwhile, the optimal ratio of steam to PC (S/P) is found to be 1.24.
Bioresource technology 01/2013; 133C:127-133. · 4.25 Impact Factor
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ABSTRACT: Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathways, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus.
Gene 01/2013; · 2.34 Impact Factor
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Ilona Obara,
Scott P Goulding,
Adam T Gould,
Kevin D Lominac,
Jia-Hua Hu,
Ping Wu Zhang,
Georg von Jonquieres,
Marlin Dehoff, Bo Xiao,
Peter H Seeburg,
Paul F Worley,
Matthias Klugmann,
Karen K Szumlinski
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ABSTRACT: Pain alters opioid reinforcement, presumably via neuroadaptations within ascending pain pathways interacting with the limbic system. Nerve injury increases expression of glutamate receptors and their associated Homer scaffolding proteins throughout the pain processing pathway. Homer proteins, and their associated glutamate receptors, regulate behavioral sensitivity to various addictive drugs. Thus, we investigated a potential role for Homers in the interactions between pain and drug reward in mice. Chronic constriction injury (CCI) of the sciatic nerve elevated Homer1b/c and/or Homer2a/b expression within all mesolimbic structures examined and for the most part, the Homer increases coincided with elevated mGluR5, GluN2A/B, and the activational state of various down-stream kinases. Behaviorally, CCI mice showed pain hypersensitivity and a conditioned place-aversion (CPA) at a low heroin dose that supported conditioned place-preference (CPP) in naïve controls. Null mutations of Homer1a, Homer1, and Homer2, as well as transgenic disruption of mGluR5-Homer interactions, either attenuated or completely blocked low-dose heroin CPP, and none of the CCI mutant strains exhibited heroin-induced CPA. However, heroin CPP did not depend upon full Homer1c expression within the nucleus accumbens (NAC), as CPP occurred in controls infused locally with small hairpin RNA-Homer1c, although intra-NAC and/or intrathecal cDNA-Homer1c, -Homer1a, and -Homer2b infusions (to best mimic CCI's effects) were sufficient to blunt heroin CPP in uninjured mice. However, arguing against a simple role for CCI-induced increases in either spinal or NAC Homer expression for heroin CPA, cDNA infusion of our various cDNA constructs either did not affect (intrathecal) or attenuated (NAC) heroin CPA. Together, these data implicate increases in glutamate receptor/Homer/kinase activity within limbic structures, perhaps outside the NAC, as possibly critical for switching the incentive motivational properties of heroin following nerve injury, which has relevance for opioid psychopharmacology in individuals suffering from neuropathic pain.
Frontiers in psychiatry / Frontiers Research Foundation. 01/2013; 4:39.
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ABSTRACT: A 40-year-old woman presented with worsening headache accompanied by vomiting, anorexia, and tinnitus. The headaches were initially orthostatic. MRI showed chronic progressive subdural hematomas (SDH) with significant mass effect, diffuse pachymeningeal enhancement, and pituitary enhancement/enlargement (figure, A and B), indicating intracranial hypotension due to spontaneous spinal CSF leak, which was confirmed by CT myelography (figure, C). CSF leak is an important cause of SDH,(1) which, by clinical and radiologic manifestations, may give the false impression that the patient has intracranial hypertension but without papilledema or hydrocephalus, termed pseudo-intracranial hypertension. This recognition is crucial because both conservative measures to decrease intracranial pressure and evacuation of the SDH are harmful.(1,2).
Neurology 01/2013; 80(1):e12. · 8.31 Impact Factor
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ABSTRACT: Myasthenia Gravis (MG) is an autoimmune disorder in which CD4(+)CD25(+) FOXP3(+)regulatory T cells (Tregs) are thought to play important roles in driving the ongoing autoimmune response. Although it is known that single-nucleotide polymorphisms (SNPs) in the fork head/winged-helix transcription factor 3 (FOXP3) gene contribute to some autoimmune diseases, information about the role of this gene in MG is limited. We therefore evaluated the association between FOXP3 gene SNPs and susceptibility to MG in a Han Chinese population. In a hospital-based, case-control study, two SNPs in the FOXP3 gene (-3279 and IVS9+459) were investigated in 118 MG and 124 healthy controls, and their relationship with the four parameters of gender, onset age, thymus pathology, and clinical classification of MG were performed with a stratified analysis. We found that the frequency of the FOXP3 IVS9+459 G allele was significantly lower in MG patients than in healthy controls (P=0.041), while the frequency of the FOXP3 -3279 polymorphisms was not significantly different between the two groups. Our results suggest that FOXP3 IVS9+459 polymorphisms appear to have an effect on the risk of MG in a Han Chinese population, and the G allele may be a genetic protective factor to MG.
Neuroscience Letters 12/2012; · 2.11 Impact Factor
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Jie Feng,
Yun-Hai Liu,
Qi-Dong Yang,
Zan-Hua Zhu,
Kun Xia,
Xing-Lin Tan,
Jian Xia,
Wen-Ping Gu,
Lin Zhou, Bo Xiao,
Bei-Sha Tang,
Qing Huang
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ABSTRACT: Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.
Journal of Thrombosis and Thrombolysis 11/2012; · 1.48 Impact Factor
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ABSTRACT: Objective: To examine the changes of metabolites in the bilateral thalamus of patients with secondarily generalized tonic-clonic seizure (SGTCS) and to explore the mechanism of SGTCS. Methods: Thirty patients with SGTCS (epilepsy group) and 30 matched healthy controls (control group) were examined by 1H-magnetic resonance spectroscopy (1H-MRS). The levels of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine phosphocreatine (Cr-PCr), and myo-inositol (mI) of the bilateral thalamus were measured in both the epilepsy group and the control group. The ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr-PCr and mI/Cr-PCr were compared and analyzed in the 2 groups. Results: The ratios of NAA/Cr-PCr, and NAA/(Cr-PCr+Cho)(1.7074 ± 0.2214; 0.9333 ± 0.2173) in the left thalamus in the epilepsy group were significantly lower than those in the control group(1.8834 ±0.2093; 1.1243 ±0.2447)(P<0.05). The ratios of NAA/Cr-PCr, and NAA/(Cr- PCr+Cho) (1.7472 ±0.2439; 0.9165 ±0.2462) in the right thalamus in the epilepsy group were also significantly lower than those in the control group(1.8925 ± 0.2004; 1.0941 ± 0.2372)(P<0.05). There were no significant differences in the ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr- PCr, and mI/Cr-PCr between the bilateral thalamis in the epilepsy group (P>0.05). Conclusion: There is neuronal dysfunction in the bilateral thalamus in the epilepsy group. Abnormal changes of the bilateral thalamus are involved in the mechanism of SGTCS.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 11/2012; 37(11):1147-51.
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ABSTRACT: To study the clinical and pathological features of children with Duchenne muscular dystrophy (DMD), with the aim of increasing the possibility of early diagnosis.
The clinical data of 50 children who were definitely diagnosed with DMD, based on clinical manifestations and the results of skeletal muscle biopsies and monoclonal antibody immunohistochemical staining, was reviewed.
The children showed similar clinical manifestations, including running slowly in the toddler period, muscle weakness when climbing stairs and standing up followed by squatting down and walking abnormalities a predominant increase in serum creatine kinase level increased dominantly, and myopathic lesions seen on electromyography. Hematoxylin-eosin staining showed similar pathological presentations in all 50 children, including different-sized muscle fibers with rounding, degeneration and necrosis in various degrees, and proliferation of connective tissues. There was some inflammatory cell infiltration in muscle fibers and interstitial tissues. Dystrophin expression was completely absent at the sarcolemma in all 50 children, and sarcoglycan-α,-β, -',-δ expression was reduced to various degrees in 33 of them.
For children with the clinical manifestations mentioned above, skeletal muscle biopsies and monoclonal antibody immunohistochemical staining are recommended as these examinations contribute to a definite diagnosis of DMD by demonstrating dystrophin deficiency at the sarcolemma.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 10/2012; 14(10):746-50.
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Neurological Sciences 09/2012; · 1.32 Impact Factor
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ABSTRACT: Exosomes, 60-90-nm-sized vesicles, are produced by a large number of cell types, including tumor cells, neurons, astrocytes, hemocytes, intestinal epithelial cells, and so on. Dendritic cell (DC), the most potent professional antigen-presenting cell in the immune system, produces exosomes in the course of maturation. Mature DCs produce exosomes with the ability to elicit potent immunoactivation, resulting in tumor eradication and bacterial or virus elimination. Given the notion that exosomes are stable and easy to be modified artificially, autologous mature DC-derived exosomes have been vaccinated into patients with malignant diseases. In clinical trials utilizing exosomes as therapeutic approaches, researchers observed considerable curative effect with little side effect. However, immature or suppressive DC-derived exosomes harbor anti-inflammatory properties distinct from mature DC-derived exosomes. In murine models of autoimmune disease and transplantation, immature DC-derived exosomes reduced T cell-dependent immunoactivation, relieved clinical manifestation of autoimmune disease, and prolonged survival time of transplantation. Although the exact mechanism of how immature DC-derived exosomes function in vivo is still unclear, and there are no clinical trials regarding application of exosome vaccine into patients with autoimmune disease, we will analyze the promise of immature DC-derived exosomes as a subcellular vaccine in autoimmunity in this review.
Inflammation 09/2012; · 1.75 Impact Factor
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ABSTRACT: Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. MiRNA let-7 family is known to be involved in the regulation of cell apoptosis. However, the function of let-7 in ox-LDL induced ECs apoptosis and atherosclerosis is still unknown. Here, we show that let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (HUVECs). Let-7c over-expression enhanced apoptosis in ECs whereas inhibition of let-7c could partly alleviate apoptotic cell death mediated by ox-LDL. Searching for how let-7c affected apoptosis, we discovered that antiapoptotic protein Bcl-xl was a direct target of let-7c in ECs. Our data suggest that let-7c contributes to endothelial apoptosis through suppression of Bcl-xl.
BMB reports 08/2012; 45(8):464-9. · 1.72 Impact Factor
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ABSTRACT: When treating patients with a spontaneous supratentorial massive (≥ 70 ml) intracerebral hemorrhage (ICH), the results of surgery are gloomy. A worsening pupil response has been observed in patients preoperatively, despite blood pressure control and diuretic administration. Because open surgery needs time for decompression to occur, the authors conducted a prospective randomized study to determine whether patients who have suffered a massive ICH can benefit from a more urgently performed decompressive procedure.
Overall, 36 eligible patients admitted 6 or fewer hours post-ictus were enrolled in the study. In Group A, 12 patients underwent CT-based hematoma puncture and partial aspiration in the emergency department (ED) and subsequent evacuation via a craniectomy; in Group B, 24 patients underwent hematoma evacuation via a craniectomy only. Pupil responses were categorized into 5 grades (Grade 0, bilaterally fixed; Grade 1, unilaterally fixed with the fixed pupil > 7 mm; Grade 2, unilaterally fixed with the fixed pupil ≤ 7 mm; Grade 3, a unilaterally sluggish response; and Grade 4, a bilaterally brisk response). Grades were obtained on admission, at surgical decompression (defined as the point at which liquid hematoma began to flow out in Group A and at dural opening in Group B), and at completion of craniectomy. The Barthel Scale was used to assess survivors' functional outcome at 12 months. Comparisons were made between Groups A and B. Logistic regression analysis was used to evaluate the positive likelihood ratio of all variables for survival and function (Barthel Scale score of ≥ 35 at 12 months).
Decompressive surgery was undertaken approximately 60 minutes earlier in Group A than B. A worsening pupil reflex before decompression was observed in no Group A patient and in 9 Group B patients. At the time of decompression pupil response was better in Group A than B (p < 0.05). Although only approximately one-third of the hematoma volume documented on initial CT scanning had been drained before the craniectomy in Group A, when partial aspiration was followed by craniectomy, better pupil-response results were obtained in Group A at the completion of craniectomy, and survival rate and 12-month Barthel Scale score were better as well (p < 0.05). Logistic regression analysis revealed that one variable, a minimum pupil grade of 3 at the time of decompression, had the highest predictive value for survival at 12 months (8.0, 95% CI 2.0-32.0), and a pupil grade of 4 at the same time was the most valuable predictor of a Barthel Scale score of 35 or greater at 12 months (15.0, 95% CI 1.9-120.9).
Patients with massive spontaneous supratentorial ICHs may benefit from more urgent surgical decompression. The results of logistic regression analysis implied that, to improve long-term functional outcome, decompression should be performed in patients before herniation occurs. Due to the fact that most of these patients have signs of herniation when presenting to the ED and because conventional surgical decompression requires time to take effect, this combination of surgical treatment provides a feasible and effective surgical option.
Journal of Neurosurgery 07/2012; 117(3):566-73. · 2.96 Impact Factor
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ABSTRACT: To investigate the effect of miR-590-5p on the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in apoptotic human umbilical vein endothelial cells (HUVECs) induced by ox-LDL, and to explore the role of miR-590-5p in modulating HUVECs apoptosis.
HUVECs were exposed to ox-LDL (50 μg/mL) for 0 to 48 h. Apoptosis was detected by Annexin V-FITC stain and was distinguished from necrosis by propidium iodide (PI) staining. The relative expression level of miR-590-5p in HUVECs was analyzed using real-time quantitative PCR (RT-qPCR). HUVECs were transfected with miR-590-5p mimics or miRNA mimics control followed by 50 μg/mL ox-LDL stimulation for 48 h. LOX-1 mRNA and protein were measured by RT-qPCR and Western blot, and apoptosis in HUVECs was analyzed by flow ctyometry after Annexin V-FITC/PI double stain.
Incubation of HUVECs with 50 μg/mL ox-LDL for 0 to 48 h resulted in a time-dependent induction of apoptotic cell death and down-regulation of miR-590-5p. Transfection of miR-590-5p mimics suppressed LOX-1 expression at both mRNA and protein levels, leading to a reduction of ox-LDL-induced apoptosis in HUVECs.
MiR-590-5p protects endothelial cells from ox-LDL induced apoptosis by inhibiting the expression of LOX-1.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 07/2012; 37(7):675-81.
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ABSTRACT: To explore the clinical and imaging features of anoxic-ischemic encephalopathy (AIE) patients after cardiopulmonary resuscitation.
A total of 28 qualified AIE patients during the last decade from Xiangya Hospital, Central South University were recruited and analyzed retrospectively.
The symptoms of status epilepticus, acute posthypoxic myoclonus, Lance-Adams syndrome, subarachnoid hemorrhage and cognitive deficits were observed. The abnormal findings of magnetic resonance imaging (MRI) or computed tomography (CT), involving neocortex, basal ganglia and para-ventricular white matter, were also recorded. During the early phase of disease, swollen cortex was present on MRI/CT. However, encephalatrophy appeared during the late phase. The more severe symptoms were observed, the more foci were present on MRI/CT.
The etiologies of AIE patients are heterogeneous after cardiopulmonary resuscitation. The clinical symptoms and imaging studies are of prognostic significance.
Zhonghua yi xue za zhi 06/2012; 92(23):1599-602.
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ABSTRACT: In this work, we sequenced the first complete mitochondrial genome of Tetrigoidea species, Alulatettix yunnanensis. The circle genome (15,104 bp) consists of 13 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes, and an A+T-rich region. It has the typical invertebrate mitochondrial gene arrangement.
Mitochondrial DNA 04/2012; 23(4):286-7. · 1.49 Impact Factor
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ABSTRACT: We have determined the complete mitochondrial genome of a species of grouse locust, Tetrix japonica. The total length of the T. japonica mitogenome is 15,128 bp with 75.57% A+T content. It consists of 13 protein-coding, 22 transfer RNA (tRNA), and 2 ribosomal RNA (rRNA) genes, and an A+T-rich region. The A+T-rich region was located between the small rRNA and tRNA-Ile genes and is 531 bp in length.
Mitochondrial DNA 04/2012; 23(4):288-9. · 1.49 Impact Factor
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Debra K Cozzoli,
Justin Courson,
Amanda L Caruana,
Bailey W Miller,
Daniel I Greentree,
Andrew B Thompson,
Melissa G Wroten,
Ping-Wu Zhang, Bo Xiao,
Jia-Hua Hu,
Matthias Klugmann,
Pamela Metten,
Paul F Worley,
John C Crabbe,
Karen K Szumlinski
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ABSTRACT: Alcohol increases the expression of Group 1 metabotropic glutamate receptors (mGluRs) and their associated scaffolding protein Homer2 and stimulates phosphatidylinositol 3-kinase (PI3K) within the nucleus accumbens (NAC). Moreover, functional studies suggest that NAC Group 1 mGluR/Homer2/PI3K signaling may be a potential target for pharmacotherapeutic intervention in alcoholism.
Immunoblotting was conducted to examine the effects of alcohol consumption under drinking-in-the-dark (DID) procedures on Group 1 mGluR-associated proteins in C57BL/6J (B6) mice. Follow-up behavioral studies examined the importance of Group 1 mGluR/Homer2/PI3K signaling within the NAC shell for limited-access alcohol drinking. Finally, immunoblotting examined whether the NAC expression of Group 1 mGluR-associated proteins is a genetic correlate of high alcohol drinking using a selectively bred high DID (HDID-1) mouse line.
Limited-access alcohol drinking under DID procedures up-regulated NAC shell Homer2 levels, concomitant with increases in mGluR5 and NR2B. Intra-NAC shell blockade of mGluR5, Homer2, or PI3K signaling, as well as transgenic disruption of the Homer binding site on mGluR5, decreased alcohol consumption in B6 mice. Moreover, transgenic disruption of the Homer binding site on mGluR5 and Homer2 deletion both prevented the attenuating effect of mGluR5 and PI3K blockade upon intake. Finally, the basal NAC shell protein expression of mGluR1 and Homer2 was increased in offspring of HDID-1 animals.
Taken together, these data further implicate Group 1 mGluR signaling through Homer2 within the NAC in excessive alcohol consumption.
Alcoholism Clinical and Experimental Research 03/2012; 36(9):1623-33. · 3.34 Impact Factor
