Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.

Major depression is associated with low bone mass and increased incidence of osteoporotic fractures. However, causality between depression and bone loss has not been established. Here, we show that mice subjected to chronic mild stress (CMS), an established model of depression in rodents, display behavioral depression accompanied by impaired bone mass and structure, as portrayed by decreases in trabecular bone volume density, trabecular number, and trabecular connectivity density assessed in the distal femoral metaphysis and L3 vertebral body. Bone remodeling analysis revealed that the CMS-induced skeletal deficiency is accompanied by restrained bone formation resulting from reduced osteoblast number. Antidepressant therapy, which prevents the behavioral responses to CMS, completely inhibits the decrease in bone formation and markedly attenuates the CMS-induced bone loss. The depression-triggered bone loss is associated with a substantial increase in bone norepinephrine levels and can be blocked by the ␤-adrenergic antagonist propranolol, suggesting that the sympathetic nervous system mediates the skeletal effects of stress-induced depression. These results define a linkage among depression, excessive adrenergic activity, and reduced bone formation, thus demonstrating an interaction among behavioral responses, the brain, and the skeleton, which leads to impaired bone structure. Together with the common occurrence of depression and bone loss in the aging population, the present data implicate depression as a potential major risk factor for osteoporosis and the associated increase in fracture incidence.antidepressant ͉ chronic depression ͉ osteoporosis ͉ bone formation ͉ adrenergic signaling

IntroductionRecent studies have shown that several strains of transgenic Alzheimer’s disease (AD) mice overexpressing the amyloid precursor protein (APP) have cortical hyperexcitability, and their results have suggested that this aberrant network activity may be a mechanism by which amyloid-β (Aβ) causes more widespread neuronal dysfunction. Specific anticonvulsant therapy reverses memory impairments in various transgenic mouse strains, but it is not known whether reduction of epileptiform activity might serve as a surrogate marker of drug efficacy for memory improvement in AD mouse models.MethodsTransgenic AD mice (APP/PS1 and 3xTg-AD) were chronically implanted with dural electroencephalography electrodes, and epileptiform activity was correlated with spatial memory function and transgene-specific pathology. The antiepileptic drugs ethosuximide and brivaracetam were tested for their ability to suppress epileptiform activity and to reverse memory impairments and synapse loss in APP/PS1 mice.ResultsWe report that in two transgenic mouse models of AD (APP/PS1 and 3xTg-AD), the presence of spike-wave discharges (SWDs) correlated with impairments in spatial memory. Both ethosuximide and brivaracetam reduce mouse SWDs, but only brivaracetam reverses memory impairments in APP/PS1 mice.ConclusionsOur data confirm an intriguing therapeutic role of anticonvulsant drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice, despite reduction of SWDs. Our data indicate that SWDs are not a reliable surrogate marker of appropriate target engagement for reversal of memory dysfunction in APP/PS1 mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-015-0110-9) contains supplementary material, which is available to authorized users.

The protein product of oncogene c-myc is believed to be important in regulation of the cell cycle. However, its direct role in DNA synthesis has not been explored. Experiments presented here show that the addition of affinity-purified antibodies against the human c-myc protein to nuclei isolated from several types of human cells reversibly inhibited DNA synthesis and DNA polymerase activity of these nuclei. This suggests that c-myc encodes a protein that is functionally involved in DNA synthesis.

Immunoreactive calcium-binding protein (CaBP) has been characterized in rat brain both biochemically and immunocytochemically. In this study antiserum to chick CaBP was used to characterize this protein and to describe its distribution in neurons and fibers of the rat fore- and midbrain. Immunostaining in neuronal elements was judged specific for this protein by the absence of staining in tissue sections after adsorption of the antiserum with either chick intestinal CaBP or the 28,000-dalton fraction from rat brain, but not with other molecular weight fractions with calcium-binding activity. Immunoreactive CaBP was found to have a widespread distribution throughout the central nervous system, and was present in most but not all major neuronal cell groups and fiber tracts. The protein was limited primarily to neuronal elements and some ependymal cells, and was absent in glia and blood vessels. The proportion of immunoreactivity in neuronal perikarya and fibers varied among nuclei and within a given structure at different rostral-caudal levels. Immunoreactivity was prominent in neocortex, hippocampal formation (primarily in CA1 and granular cells of the dentate gyrus), hypothalamus, and amygdala. These areas are responsible for the regulation of a variety of pituitary hormones, and several bind steroids. Immunoreactive CaBP was also a major constituent of nonlimbic system pathways. The widespread distribution of immunoreactive CaBP in the central nervous system suggests that CaBP and the vitamin D endocrine system may play a significant role in the regulation of mammalian brain function.