Maternal immune activation alters visual acuity and retinogeniculate axon pruning in offspring mice.

Individuals with autism spectrum disorder (ASD) have been found to have a variety of sensory processing deficits. Here we report that maternal immune activation, a known factor for ASD, alters visual acuity in the offspring mice. By intraperitoneally injecting polyinosinic-polycytidylic acid (polyI:C) to induce maternal immune activation during embryonic days 10 to 14, we found that polyI:C treatment impairs visual acuity in young adult offspring mice as examined by their optomotor responses. Concurrently, polyI:C treatment suppresses retinogeniculate axon elimination, resulting in a high fraction of weak optical fibers innervating the relay neurons in the visual thalamus. The results link in-utero maternal inflammation to defective optical fiber pruning and arrested developmental strengthening of single optic fibers which may underlie impaired visual acuity.

Amyloid ß oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate.

Amyloid ß (Aß) oligomer-induced aberrant neurotransmitter release is proposed to be a crucial early event leading to synapse dysfunction in Alzheimer's disease (AD). In the present study, we report that the release probability (Pr) at the synapse between the Schaffer collateral (SC) and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aß production. High nanomolar synthetic oligomeric Aß42 also suppresses Pr at the SC-CA1 synapse in wild-type mice. This Aß-induced suppression of Pr is mainly due to an mGluR5-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) in axons. Selectively inhibiting Aß-induced PIP2 hydrolysis in the CA3 region of the hippocampus strongly prevents oligomeric Aß-induced suppression of Pr at the SC-CA1 synapse and rescues synaptic and spatial learning and memory deficits in APP/PS1 mice. These results first reveal the presynaptic mGluR5-PIP2 pathway whereby oligomeric Aß induces early synaptic deficits in AD.

Splenic abscess owing to cancer at the splenic flexure: A case report and comprehensive review.

BACKGROUND: The cancer of the splenic flexure of the colon is a rare medical entity with severe morbidity because of its insidious onset. METHODS: We present the case of a 59-year-old male patient with dull left upper quadrant pain, leukocytosis, and anemia. A splenic abscess described as an air-fluid level with splenocolic fistula was found on CT scan imaging. Surgery was done for splenic pus drainage. He was again admitted 2 months later for intestinal obstruction. RESULTS: An exploratory laparotomy showed multiple hard, gray liver nodules as well as a hard mass in the small bowel. Owing to extensive adhesions and a late stage of cancer involvement, the splenic flexure tumor was not resected. A loop transverse colostomy was done and a Coloplast Colostomy bag placed. We also reviewed the literature-linking colon cancer and splenic abscess with specific attention to the carcinoma of the splenic flexure. As the latter invades through the spleen matter, there is the creation of a splenocolic fistula, which allows the migration of normal gut flora into the spleen. This leads to the formation of the splenic abscess. CONCLUSION: This is the 13 case report pertaining to invading colonic cancer causing a splenic abscess. Although the treatment for splenic abscesses is shifting from splenectomy to image-guided percutaneous pus drainage, the few reported cases make the proper management of such complication still unclear.

miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.

Recent studies have revealed the critical role of microRNAs (miRNAs) in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1) has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg) mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1) were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion). The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε) and heat shock protein 60 (HSP60). In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.

MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-ß1 pathway.

BACKGROUND: Cardiac interstitial fibrosis is a major cause of the deteriorated performance of the heart in patients with chronic myocardial infarction. MicroRNAs (miRs) have recently been proven to be a novel class of regulators of cardiovascular diseases, including those associated with cardiac fibrosis. This study aimed to explore the role of miR-101 in cardiac fibrosis and the underlying mechanisms. METHODS AND RESULTS: Four weeks after coronary artery ligation of rats, the expression of miR-101a and miR-101b (miR-101a/b) in the peri-infarct area was decreased. Treatment of cultured rat neonatal cardiac fibroblasts with angiotensin II also suppressed the expression of miR-101a/b. Forced expression of miR-101a/b suppressed the proliferation and collagen production in rat neonatal cardiac fibroblasts, as revealed by cell counting, MTT assay, and quantitative reverse transcription-polymerase chain reaction. The effect was abrogated by cotransfection with AMO-101a/b, the antisense inhibitors of miR-101a/b. c-Fos was found to be a target of miR-101a because overexpression of miR-101a decreased the protein and mRNA levels of c-Fos and its downstream protein transforming growth factor-ß1. Silencing c-Fos by siRNA mimicked the antifibrotic action of miR-101a, whereas forced expression of c-Fos protein canceled the effect of miR-101a in cultured cardiac fibroblasts. Strikingly, echocardiography and hemodynamic measurements indicated remarkable improvement of the cardiac performance 4 weeks after adenovirus-mediated overexpression of miR-101a in rats with chronic myocardial infarction. Furthermore, the interstitial fibrosis was alleviated and the expression of c-Fos and transforming growth factor-ß1 was inhibited. CONCLUSION: Overexpression of miR-101a can mitigate interstitial fibrosis and the deterioration of cardiac performance in postinfarct rats, indicating the therapeutic potential of miR-101a for cardiac disease associated with fibrosis.