Astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits. Astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction. Heterosynaptic long-term depression (hLTD) at synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation. Heterosynaptic long-term depression in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from synaptic terminals via activation of P2Y receptors. Selective stimulation of astrocytes resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors. Blocking P2Y receptors or buffering astrocyte intracellular Ca(2+) at a low level prevented hLTD without affecting LTP

Chronic psychological stress may contribute to the development of atherosclerosis by enhancing vascular inflammation and decreasing endothelial nitric oxide bioavailability. Unpredictable chronic mild stress (UCMS) exposure significantly increased the plaque size (p = .003) and decreased the plaque stability (decreased the contents of collagen and smooth muscle and increased the amount of macrophage and matrix metalloproteinases). The proatherogenic effects of UCMS were unrelated to changes in serum cholesterol level but accompanied by increased blood pressure (p < .001) and vascular inflammation (up-regulation of tumor necrosis factor α, C-reactive protein, and monocyte chemoattractant protein 1, all p values < .01). Serum concentrations of nitrate/nitrite were lower in UCMS-treated animals (p = .01). Vessels from UCMS-treated animals exhibited augmented phosphorylation of p38 and c-Jun N-terminal kinase and activation of nuclear factor κB.

Vitamin D deficiency is a potential risk factor for cardiometabolic disease. Vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia. Vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (β: -0.029 [-0.049, -0.0091], P=.004) and triglyceride (β: -0.094 [-0.15, -0.039] P=.001) levels. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P=.014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P <.001) in adjusted models.

Abdominal migraine is a diagnostically challenging disorder, characterized by recurrent episodes of abdominal pain. Our findings demonstrate that abdominal migraine occurs and should be considered in the differential diagnosis of recurrent abdominal pain in adults, especially if there is a family history of migraine headaches.

Growth hormone-releasing hormone (GHRH), growth hormone, and insulinlike growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI). The intent-to-treat analysis indicated a favorable effect of GHRH on cognition which was comparable in adults with MCI and healthy older adults. Subsequent analyses indicated a positive GHRH effect on executive function and a trend showing a similar treatment-related benefit in verbal memory. Treatment with GHRH increased insulinlike growth factor 1 levels by 117%, which remained within the physiological range, and reduced percent body fat by 7.4%. Treatment with GHRH increased fasting insulin levels within the normal range by 35% in adults with MCI but not in healthy adults. Adverse events were mild and were reported by 68% of GHRH-treated adults and 36% of those who received placebo.

Alzheimer’s disease (AD) is characterized by the accumulation of the β-amyloid peptide (Aβ), which is generated from sequential cleavages of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Increased very long chain fatty acid (VLCFA) levels in AD brains imply that peroxisomal β-oxidation dysfunction may be associated with AD pathogenesis. Thioridazine is a selective peroxisomal β-oxidation inhibitor. Thioridazine caused VLCFA accumulation and increases in Aβ(40) content, APP immunoreactivity and APP(751+770) mRNA expressions in the rat cerebral cortex. Impaired peroxisomal function may play an important role in the progression of AD pathology.

Autoimmune thyrotoxicosis or Graves’ disease (GD) is the most common cause of hyperthyroidism in the United States. GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders.

Untreated maternal depression was associated with slower rates of fetal body and head growth. Pregnant mothers treated with SSRIs had fewer depressive symptoms and their fetuses had no delay in body growth but had delayed head growth and were at increased risk for preterm birth.

Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10-year risk of ischemic stroke among healthy middle-aged men. Resistin, adipsin, and total adiponectin, but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin.

There is significant evidence for a central role of inflammation in the development of Alzheimer disease (AD). Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. Stimulation of the the PGE(2) EP3 receptor activates proinflammatory, proamyloidogenic, and synaptotoxic signaling pathways. Deletion of the PGE(2) EP3 receptor in a model of Aβ(42) peptide-induced neuroinflammation reduced proinflammatory gene expression, cytokine production, and oxidative stress. Deletion of the EP3 receptor blocked induction of proinflammatory gene and protein expression and lipid peroxidation, and levels of Aβ peptides were significantly decreased, as were β-secretase and β C-terminal fragment levels.