Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types.

Aging is a complex process involving transcriptomic changes associated with deterioration across multiple tissues and organs, including the brain. Recent studies using heterochronic parabiosis have shown that various aspects of aging-associated decline are modifiable or even reversible. To better understand how this occurs, we performed single-cell transcriptomic profiling of young and old mouse brains after parabiosis. For each cell type, we cataloged alterations in gene expression, molecular pathways, transcriptional networks, ligand-receptor interactions and senescence status. Our analyses identified gene signatures, demonstrating that heterochronic parabiosis regulates several hallmarks of aging in a cell-type-specific manner. Brain endothelial cells were found to be especially malleable to this intervention, exhibiting dynamic transcriptional changes that affect vascular structure and function. These findings suggest new strategies for slowing deterioration and driving regeneration in the aging brain through approaches that do not rely on disease-specific mechanisms or actions of individual circulating factors.

A load-based thermopower measurement setup in the temperature range of 5-330 K.

This is a report on the development of an automated precision load-based measurement setup for thermoelectric power (S) of different types of samples in the temperature range of 5-330 K. The problems in the old spring-based setup have been solved in this load-based setup. This setup takes nearly 4 h for each run, and the typical error is within 5%. High quality calibration has been demonstrated using high purity platinum wires and cylinders.

Perturbation of canonical and non-canonical BMP signaling affects migration, polarity and dendritogenesis of mouse cortical neurons.

Bone morphogenetic protein (BMP) signaling has been implicated in the regulation of patterning of the forebrain and as a regulator of neurogenesis and gliogenesis in the mammalian cortex. However, its role in other aspects of cortical development in vivo remains unexplored. We hypothesized that BMP signaling might regulate additional processes during the development of cortical neurons after observing active BMP signaling in a spatiotemporally dynamic pattern in the mouse cortex. Our investigation revealed that BMP signaling specifically regulates the migration, polarity and the dendritic morphology of upper layer cortical neurons born at E15.5. On further dissection of the role of canonical and non-canonical BMP signaling in each of these processes, we found that migration of these neurons is regulated by both pathways. Their polarity, however, appears to be affected more strongly by canonical BMP signaling, whereas dendritic branch formation appears to be somewhat more strongly affected by LIMK-mediated non-canonical BMP signaling.

Identification of novel candidate regulators of retinotectal map formation through transcriptional profiling of the chick optic tectum.

Information from the retina is carried along the visual pathway with accuracy and spatial conservation as a result of topographically mapped axonal connections. The optic tectum in the midbrain is the primary region to which retinal ganglion cells project their axons in the chick. The two primary axes of the retina project independently onto the tectum using different sets of guidance cues to give rise to the retinotectal map. Specificity of the map is determined by attractive or repulsive interactions between molecular tags that are distributed in gradients in the retina and the tectum. Despite several studies, knowledge of the retinotectal guidance molecules is far from being complete. We screened for all molecules that are expressed differentially along the anterior-posterior and medial-lateral axes of the chick tectum using microarray based transcriptional profiling and identified several novel candidate retinotectal guidance molecules. Two such genes, encoding Wnt5a and Raldh2, the synthesizing enzymes for retinoic acid, were further analyzed for their function as putative regulators of retinotectal map formation. Wnt5a and retinoic acid were found to exhibit differential effects on the growth of axons from retinal explants derived from different quadrants of the retina. This screen also yielded a large number of genes expressed in a lamina-specific manner in the tectum, which may have other roles in tectal development. J. Comp. Neurol. 525:459-477, 2017. © 2016 Wiley Periodicals, Inc.

Mouse bone marrow stromal cells differentiate to neuron-like cells upon inhibition of BMP signaling.

Bone marrow stromal cells (BMSCs) are a source of autologous stem cells that have the potential for undergoing differentiation into multiple cell types including neurons. Although the neuronal differentiation of mesenchymal stem cells has been studied for a long time, the molecular players involved are still not defined. Here we report that the genetic deletion of two members of the bone morphogenetic protein (Bmp) family, Bmp2 and Bmp4 in mouse BMSCs causes their differentiation into cells with neuron-like morphology. Surprisingly these cells expressed certain markers characteristic of both neuronal and glial cells. Based on this observation, we inhibited BMP signaling in mouse BMSCs through a brief exposure to Noggin protein which also led to their differentiation into cells expressing both neuronal and glial markers. Such cells seem to have the potential for further differentiation into subtypes of neuronal and glial cells and thus could be utilized for cell-based therapeutic applications.

Jaggery protects hepatorenal injury induced by acute exposure to carbon tetrachloride in Wistar rats.

In this study, we evaluated the protective activity of aqueous extract of jaggery against CCl4-induced hepatic-renal damage in rats. Jaggery was administered in one group at doses of 250, 500 and 750 mg/ kg body weight (bwt) (p.o., once only), and CCL4 was administered in another group at a dose of 1.5 ml/kg bwt (i.p., once only) to evaluate the protective effect of jaggery on induced oxidative damage in rats. Various blood and tissue biochemical studies were performed. The administration of toxicant significantly altered blood biochemical variables. Hepatic and renal lipid peroxidation (LPO) levels increased significantly, whereas considerable depletion was observed in reduced glutathione (GSH) level after intoxication. A remarkable decrease was observed in the activities of adenosine triphosphatase (ATPase) and glucose-6-phosphatase (G-6-Pase) after induction of toxicity. Treatment with extract at three different altered all measured biochemical variables, but greater hepatic-renal protection was observed at higher doses (750 mg/kg bwt) than at lower does (250 and 500 mg/kg bwt). Jaggery also reversed histopathological alterations. Thus, it may be concluded that jaggery can be used to reduce hepatic and renal damage and may serve as an alternative medicine in hepatic and renal etiology.

Hepatoprotective efficacy of Sharbat-e-Deenar against carbon tetrachloride-induced liver damage.

This study was undertaken to evaluate the antioxidant and hepatoprotective efficacy of Sharbat-e-Deenar (SD) against carbon tetrachloride (CCl(4))-induced hepatic damage in a rat model. The antioxidant activity of SD was estimated by DPPH assay, H(2)O(2) assay, and total phenolic contents. SD therapy at doses of 1, 2, and 4 mL/kg, orally, was administered after CCl(4) intoxication (1.5 mL/kg, intraperitoneally for 48 hours) in experimental animals. Hexobarbitone sleep time and bromosulfophthalein retention time also were determined against CCl(4)-induced liver damage. Exposure to CCl(4) in experimental animals showed biochemical and histopathological deterioration in the liver. Treatment with SD showed a marked protection on biochemical parameters, that is, alanine transaminase, aspartate transaminase, albumin, and urea. SD therapy exhibited a protective effect by restoring the level of lipid peroxidation-reduced glutathione, adenosine triphosphate, and glucose-6-phosphatase (G-6-Pase). Treatment with SD significantly recovered the level of hexobarbitone sleep time and bromosulfophthalein retention time. DPPH and H(2)O(2) assays showed antioxidant properties in a dose-dependent manner. Histopathological observations of liver sections showed recovery in liver architecture after SD treatment. These results indicate that SD exerts a protective effect on CCl(4)-induced hepatotoxicity, which may be due to its antioxidant properties.

Defining structural homology between the mammalian and avian hippocampus through conserved gene expression patterns observed in the chick embryo.

The mammalian hippocampus, a center of neurogenesis in the adult brain, is involved in critical functions such as learning and memory processing. Although there is an overall functional conservation between birds and mammals in the hippocampal region of the brain, there are several morphological differences. A few different models have been proposed for identifying regional and structural homology between the avian and mammalian hippocampus however a consensus is yet to be reached. In this study we have systematically and comprehensively characterized the developing chicken hippocampus at the molecular level. We have identified the time window of neurogenesis and apoptosis during hippocampal development as well as the likely origin and migration path of neurons of the ventral v-shaped region of chick hippocampus. In addition to this we have identified several genes with expression patterns that are conserved between the hippocampus of chicken and mice. Our study provides molecular data that partially supports one of the models reported in literature for structural homology between the avian and mammalian hippocampus. Functional characterization of the genes found in this study to be specifically expressed in the developing chicken hippocampus is likely to provide valuable information on the mechanisms regulating hippocampus development of birds and perhaps could be extrapolated to mammalian hippocampus development as well.

Reversal of carbon tetrachloride-induced hepatic injury by aqueous extract of Artemisia absinthium in Sprague-Dawley rats.

In the present study, we evaluated the protective activity of an aqueous extract of Artemisia absinthium against CCl4-induced hepatic damage in rats. The protective activity of this extract at three doses (2.5, 5, and 10 ml/ kg, once orally) against CCl4-induced oxidative damage (1.5 ml/kg, once intraperitoneally) in rats was analyzed. Various blood and tissue biochemical studies were performed, and the administration of the toxicant significantly altered blood biochemical variables. Hepatic lipid peroxidation (LPO) was significantly elevated, whereas glutathione (GSH) level was considerable depleted after intoxication. Remarkable decreases in the activities of adenosine triphosphatase (ATPase) and glucose-6-phosphatase (G-6-Pase) after intoxication were observed. Treatment with all three doses reversed altered tissue biochemical values, but the greatest protection was observed at the lowest dose (2.5 ml/kg). The results of this study show that A. absinthium induces strong hepatoprotective activity. It decreased the hexobarbitone-induced sleep time and improved cholerectic activity (bile flow and bile solids) and excretory capacity, and it also stimulated bile secretion. The potent antioxidant activity of A. absinthium was indicated by scavenging effects on 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydrogen peroxide (H2O2). Thus, be considered for use in reducing hepatic damage and may serve as an alternative medicine in hepatic etiologies.

Evaluation of the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward against carbon tetrachloride induced liver injury.

The present study was designed to demonstrate the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward, a Unani herbal formulation. The Majoon-e-Dabeed-ul-ward (MD) at the doses of 250, 500 and 1000 mg/kg, p.o. was administered after carbon-tetrachloride (CCl(4); 1.5 ml/kg, i.p. once only) intoxication. Treatment with MD at three doses brought the levels of aspartate transaminase, alanine transaminase, albumin and urea in dose dependent manner. Signification reduction was found in TBARS content and restored the level of reduced glutathione, adenosine triphosphatase, and glucose-6-phosphatase in liver. Therapy of MD showed its protective effect on biochemical and histopathological observation at all the three doses in a dose dependent manner. The study conducted showed that MD possesses strong hepatoprotective activity as decrease the hexobarbitone sleep time and improvement in physiological parameter, excretory capacity (BSP retention time) was seen. DPPH and H(2)O(2) scavenging effects indicated its potent antioxidant activities. The results revealed that MD could afford significant dose-dependent protection against CCl(4) induced hepatocellular injury.

Therapeutic efficacy of Rosa damascena Mill. on acetaminophen-induced oxidative stress in albino rats.

Rosa damascena (RD) is a widely cultivated ornamental plant. It acts as an astringent, aperients, carminative, and refrigerant and is used in respiratory disorders, tonsillitis, eye disorders, migraines, gynecological disorders, and menopausal symptoms. The aim of this study is to investigate the hepatoprotective activity of the aqueous extract of RD flowers at different oral dose levels (250, 500, and 1000 mg/kg body weight) on acetaminophen (2 g/kg oral N-acetyl-p-aminophenol [APAP])-induced toxicity in rats. APAP administration altered various biochemical parameters, including serum transaminases, serum alkaline phosphatase, lactate dehydrogenase, albumin, bilirubin, urea and creatinine, hepatic lipid peroxidation, and reduced glutathione levels. Adenosine triphosphatase and glucose-6-phosphatase activity in the liver was decreased significantly in animals treated with APAP. These values are retrieved significantly by treatment with RD extract at all 3 doses in dose-dependant manner. Apart from these, histopathological changes also reveal the protective nature of the RD extract against acetaminophen-induced necrotic damage of hepatic tissues. In conclusion, these data suggest that the aqueous extract of RD may prevent hepatic damage from APAP-induced toxicity in rats and is likely to be mediated through its antioxidant activities.

CDK5: the "pathfinder" for new born neurons in adult hippocampus?

Neurogenesis takes place in the mammalian hippocampus throughout the whole life and deficient adult hippocampal neurogenesis has been related to neurological conditions like Alzheimer disease (AD), Parkinson disease (PD) and epilepsy. The molecular mechanisms by which immature neurons and their extending neurites find their appropriate position and target area remain largely unknown. Recent work by Jessberger et al. examines the role of Cdk5 in normal adult neurogenesis by a retroviral knock-down approach. Cdk5 is shown to be implicated in the migration of newborn neurons into the granule cell layer (GCL), as well as, in correct targeting of dendrites from newborn granule cells (GC) into the molecular layer (ML) of the dentate gyrus (DG). The study also shows that aberrant dendrites still seem to become synaptically integrated into the existing circuitry thereby suggesting a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation. The finding of Cdk5 guiding this integration of new born neurons at the physiologically appropriate place is an important step towards understanding adult neurogenesis that may help to overcome problems with the restorative use of neural stem cells in present grafting approaches in neurological diseases.