Central angiotensin II has catabolic action at white and brown adipose tissue

Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and β(3)-adrenergic receptor expression in brown adipose tissue and β3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue.     

Corticosteroids and the brain

Mineralocorticoid (MR) and glucocorticoid receptors (GR) are expressed in the central nervous system. Radioligand binding studies, autoradiography, immunocytochemistry and in situ hybridization have shown that MR and GR are found in abundance in neurons of the limbic system (hippocampus), a structure involved in mood, affect and subtle control of the hypothalamic-pituitary-adrenal (HPA) axis. In the hippocampus MR binds corticosterone (CORT) as well as aldosterone (ALDO) with high affinity. MR seems mainly occupied by CORT in the face of its 2-3 order higher circulating concentration. GR binds CORT with a 6-10-fold lower affinity. MR and GR gene expression, as well as the native receptor proteins, seem to be controlled in a coordinative manner. When GR is down-regulated by excess homologous steroid, MR appears to be increased. Down regulation of MR reduces GR as well. MR and GR display a differential ontogenetic pattern. Ontogeny, particularly that of GR, can be permanently influenced when animals are exposed during the first post-natal week of maternal deprivation, handling, CORT or ACTH1-24 injections. These MR and GR changes persist into senescence and have been proposed to result in altered CORT responsiveness, stress regulation, behavioural adaptation and brain aging.     

Superkiller yeast strain contains additional species of double-stranded RNA

A superkiller yeast strain, T158C, was found to contain four new species of ds RNA designated P3, P4, P5, and P6. The new components were found to have molecular weights of 880,000 daltons, 620,000 daltons, 500,000 daltons, and 330,000 daltons, respectively. The new species were shown to be double-stranded RNA by their resistance to pancreatic RNAse (E.C.3.1.4.22) in high salt and their sensitivity in low salt. Curing of the killer character by growth at high temperature resulted in the loss of P3–6 as well as M ds RNA. Since T158C is a superkiller, these new molecules may play an important role in the expression of the killer character.     

Hippocampal Neuropathology of Diabetes Mellitus is Relieved by Estrogen Treatment

1. A recently recognized complication of uncontrolled diabetes mellitus is the encephalopathy involving, among other regions, the hippocampus. Since estrogens bring neuroprotection in cases of brain injury and degenerative diseases, we have studied if estradiol (E2) administration counteracts some hippocampal abnormalities of streptozotocin (STZ)-diabetic adult mice.2. We first report the ability of E2 to modulate neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ) of diabetic mice. Using bromodeoxyuridine (BrdU) to label newly generated cells, a strong reduction in cell proliferation was obtained in DG and SVZ of mice sacrificed 20 days after STZ administration. The reduction was completely relieved by 10 days of E2 pellet implantation, which increased 30-fold the circulating E2 levels.3. Diabetic mice also showed abnormal expression of astrocyte markers in hippocampus. Thus, increased number of GFAP⁺ cells, indicative of astrogliosis, and increased number of apolipoprotein-E (Apo-E)⁺ astrocytes, a marker of ongoing neuronal dysfunction, was found in stratum radiatum below the CA1 hippocampal subfield of diabetic mice. Both parameters were reverted to normal by the E2 regime that upregulated cell proliferation.4. The studies demonstrated that hippocampal neuropathology of uncontrolled diabetes is a reversible condition and sensitive to estrogen treatment. Studies in animal models may open up new venues for understanding the beneficial role of steroid hormones in diabetic encephalopathy.     

The evolution of the spindlin gene in birds: sequence analysis of an intron of the spindlin W and Z gene reveals four major divisions of the Psittaciformes

The Psittaciformes (parrots, parakeets) are among the most widely held captive birds. Yet, their evolution and their phylogenetic relationships have been relatively little studied. This paper describes the phylogenetic relationships between a number of Psittaciformes as derived from the sequences of the third intron of the Z-chromosomal and W-chromosomal spindlin genes. The Z-chromosomal sequences of the kakapo (Strigops habroptilus), the kea (Nestor notabilis), and the kaka (Nestor meridionalis) from New Zealand form a cluster which is the sister group to all other Psittaciformes. The results show further that the Z-chromosomal sequences of the other species can be divided into two groups based on the occurrence of a sequence element ACCCT. The group with the insert (A) is mainly from species with an Australasian geographical distribution and includes such species as the Lories (Lorius, etc.), the budgerigar (Melospittacus undulatus), and the rosellas (Platycercus). It also includes the African lovebirds (Agapornidae), which are the only representative of group A outside Australasia. Group B, without the insert, includes the neotropical parrots and parakeets such as the amazons (Amazona, etc.), the macaws (Ara, etc.), and the conures (Aratinga, etc.), the Australian Cacatuini and the African species such as the African grey parrot (Psittacus erithacus) as well as Coracopsis vasa from Madagascar and Psittrichas fulgidus from New Guinea. The W-chromosomal sequence data show that another division of the Psittacidae is found in the replacement of a pyrimidine-rich segment occurring in many non-psittacines as well as the kakapo (S. habroptilus), the kea (N. notabilis), the kaka (N. meridionalis), and the Cacatuini by a microsatellite consisting of a variable number of TATTA monomers in the other Psittaciformes. The results support a Gondwanan origin of the Psittaciformes and the suggestion that paleogeographic events were a major force in psittacine divergence.     

The amount of free corticosterone is increased during lipopolysaccharide-induced fever

The relation between lipopolysaccharide (LPS)-induced fever and bioavailability of corticosterone (B) was examined in male Wistar rats. Animals were injected with LPS (2.5 mg/kg i.p.) or saline and core temperature and heart rate were monitored continuously using a biotelemetry system. Blood samples were withdrawn from freely moving rats via jugular catheters for estimation of total and free plasma B. LPS induced a long-lasting increase (24-48 h) in core temperature and B secretion and a short-lasting increase (90 min) in heart rate. LPS-induced fever was accompanied by a significant increase in the free/total B ratio. In contrast, an acute injection of B, which resulted in circulating B levels similar to those found after LPS, did not affect the free/total B ratio. The important role of LPS-induced fever in the hormone secretion pattern and the equilibrium between free and total B was further demonstrated in an in vitro study showing that an increase in the temperature by 3 degrees C elevated the free B fraction and the free/total B ratio of plasma samples with concentrations of B in the physiological range (5-40 microg/dl). Taken together, these findings indicate that during LPS-induced fever there is an increase in the amount of biologically available B. Exposure of glucocorticoid-sensitive targets to elevated levels of free B could contribute to the restoration of homeostasis that is disturbed during inflammation.