The pharmacology of neurosteroidogenesis

In adrenal cortex and other steroidogenic tissues including glial cells, the conversion of cholesterol into pregnenolone is catalyzed by the cytochrome P450_scc located in the inner mitochondrial membrane. A complex mechanism operative in regulating cholesterol access to P450_scc limits the rate of pregnenolone biosynthesis. Participating in this mechanism are DBI (diazepam binding inhibitor), an endogenous peptide that is highly expressed in steroidogenic cells and some of the DBI processing products including DBI 17–50 (TTN). DBI and TTN activate steroidogenesis by binding to a specific receptor located in the outer mitochondrial membrane, termed mitochondrial DBI receptor complex (MDRC). MDRC is a hetero-oligomeric protein: only the subunit that includes the DBI and benzodiazepine (BZD) recognition sites has been cloned. Several 2-aryl-3-indoleacetamide derivatives (FGIN-1-X) with highly selective affinity (nM) for MDRC were synthesized which can stimulate steroidogenesis in mitochondrial preparations. These compounds stimulate adrenal cortex steroidogenesis in hypophysectomized rats but not in intact animals. Moreover, this steroidogenesis is inhibited by the isoquinoline carboxamide derivative PK 11195, a specific high affinity ligand for MDRC with a low intrinsic steroidogenic activity. Some of the FGIN-1-X derivatives stimulate brain pregnenolone accumulation in adrenalectomized-castrated rats. The FGIN-1-X derivatives that increase brain pregnenolone content, elicit antineophobic activity and antagonize punished behavior in the Vogel conflict test in rats. These actions of FGIN-1-X are resistant to inhibition by flumazenil, a specific inhibitor of BZD action in GABA_A receptors but are antagonized by PK 11195, a specific blocker of the steroidogenesis activation via MDRC stimulation. It is postulated that the pharmacological action of FGIN-1-X depends on a positive modulation of the GABA action on GABA_A receptors mediated by the stimulation of brain neurosteroid production.     

Mapping of human hexokinase 1 gene to 10q11----qter.

Two partial-length cDNAs encoding the type 1 human hexokinase (ATP:D-hexose 6-phosphotransferase) were isolated from a placenta cDNA library using a 50-bp oligonucleotide synthesized according to the known sequence of human HK1. Using the larger (1.8 kb) cDNA insert as a probe and a panel of human-hamster somatic cell hybrids, we were able to assign the HK1 gene to the long arm of chromosome 10.     

Vagrant Subantarctic fur seal at Cape Shirreff,Livingston Island,Antarctica

A vagrant adult male Subantarctic fur seal Arctocephalus tropicalis was observed among Antarctic fur seals A. gazella at Cape Shirreff, Livingston Island, Antarctica, which is located to ~4,190 and ~5,939 km from the nearest breeding colonies of Subantarctic fur seals. Although the colony of origin of this animal and the reason for its movement outside its distribution range are unknown, this sighting shows the high dispersal capacity of this species and provides an insight into possible changes in its distribution. Although this vagrant was not observed with females Antarctic fur seal, news sightings in the future could result in viable hybrid, and introgressive hybridization could represent a threat for Cape Shirreff population recovery, if still the population way to go to recover to presailing levels.     

Enhanced glutamate,IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT,GABA and bone marrow cell supplementation

Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in B_max (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.     

2,4-Trans-4,5-trans-4,5-dihydroxypipecolic acid and cis-5-hydroxypipecolic acid from leaves of Calliandra angustifolia and sap of C. Confusa

2,4-Trans-4,5-trans-4,5-dihydroxypipecolic acid and cis-5-hydroxypipecolic acid have been isolated from the leaves of Calliandra angustifolia and the sap of C. confusa. Distribution of these and other non-protein amino acids is discussed.     

Calaminthadiol,a new 3,4-secotriterpenoid from Satureia calamintha and Satureia graeca

A new triterpenoid, calaminthadiol, 3,4-seco-4(23),12-ursadien-3,28-diol, was isolated from the leaves of Satureia calamintha and Satureia graeca. Its structure was elucidated by spectroscopic methods and partial synthesis. The natural occurrence of this compound can be conclusive for the chemotaxonomic characterization of the genus because of the rarity of the 3,4-fission in the α- and β-amyrin skeletons. A biogenetic mechanism for its formation is proposed. Sitosterol, stigmasterol and campesterol were also isolated.     

Lunar phobia in bats and its ecological correlates: A meta-analysis

Animals show several behavioral strategies to reduce predation risks. Presumably, moonlight avoidance is a strategy used by some nocturnal species to reduce the risk of predation. In bats, some research indicates that foraging activity is negatively correlated with moonlight intensity, a phenomenon better known as lunar phobia. However, the currently available evidence is contradictory because some bat species reduce their activity during nights with more moonlight while the opposite occurs in other species. We quantitatively evaluated the strength and direction of the relationship between moonlight intensity and bat activity using a meta-analysis. We also looked at some ecological correlates of lunar phobia in bats. Specifically, we examined foraging habitat and latitude as potential moderators of the size of the lunar phobia effect. Our results show that, regardless of the method used to evaluate bat activity, the overall relationship between moonlight intensity and bat activity is significant and negative (r = ?0.22). Species foraging on the surface of the water (piscivores and insectivores; r = ?0.83) and forest canopy species (i.e., big frugivores; r = ?0.30) are more affected by moonlight than those with different foraging habitats (understory, subcanopy, open air). Latitude was positively correlated with lunar phobia (r = 0.023). The stronger lunar phobia for bats foraging on the water surface and in the forest canopy may suggest that the risk of predation is greater where moonlight penetrates more easily. The significant effect of latitude as a moderator of lunar phobia suggests that there is a weak geographic pattern, with this phobia slightly more common in tropical bats than in temperate species.