Release of Endogenous Amino Acids from the Hippocampus and Brain Stem from Developing and Adult Mice in Ischemia

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K⁺-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, l-glutamate and l-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active l-glutamine, l-alanine, l-threonine and l-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K⁺ stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.     

Correlation of (Ordovician, Mohawkian) K-bentonites in the upper Mississippi valley using apatite chemistry: implications for stratigraphic interpretation of the mixed carbonate-siliciclastic Decorah Formation

Four Ordovician K-bentonites have been chemically fingerprinted using trace element content of apatite phenocrysts contained within the altered ash layers. Trace element analysis was performed using electron microprobe on individual crystals. The bentonites include the Deicke, Millbrig, Elkport, and Dickeyville beds. These beds lie within the Decorah Formation of the northern Mississippi Valley outcrop area. All four K-bentonite beds are believed to have a Taconic source whereas volcanic ash was transported by wind and deposited in the Ordovician North America epeiric sea.

The Decorah is a marine unit, shaly to the north and west and carbonate-rich to the south and east. Thirteen K-bentonite samples were collected from six localities. Only one locality (Dickeyville, WI) contains all four beds in succession. One hundred seventy-one apatite crystals were handpicked and analyzed for major, minor and trace elements using an electron microprobe. Each crystal was analyzed at three to six separate spots to ascertain compositional variation. The most discriminating and diagnostic elements were Mg and Mn; plotting Mg vs. Mn content produces data clusters characteristic for each K-bentonite. Clusters show only minimal change between localities, allowing individual K-bentonites to be identified and used for stratigraphic correlation.

Time slices provided by the K-bentonite horizons show that the Decorah Formation is composed of reciprocal wedges (stratigraphic sequences) of shale and carbonate. Shale was deposited in deeper water within the Hollandale Embayment but pinched out southeastward onto the flank of the Wisconsin Dome. Carbonates were formed largely in shoal water on the arch, prograding northwestward and shaling out downramp into the embayment.     

Evidence of PPII-like helical conformation and glass transition in a self-assembled solid-state polypeptide-surfactant complex: poly(L-histidine)/docylbenzenesulfonic acid

We present lamellar self-assembly of cationic poly(L-histidine) (PLH) stoichiometrically complexed with an anionic surfactant, dodecyl benzenesulfonic acid (DBSA), which allows a stabilized conformation reminiscent of polyproline type II (PPII) left-handed helices. Such a conformation has no intrapeptide hydrogen bonds, and it has previously been found to be one source of flexibility, e.g., in collagen and elastin, as well as an intermediate in silk processing. PLH(DBSA)1.0 complexes were characterized by Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The PPII-like conformation in PLH(DBSA)1.0 is revealed by characteristic CD and FTIR spectra, where the latter indicates absence of intrachain peptide hydrogen bonds. In addition, a glass transition was directly verified by DSC at ca. 135 degrees C for PLH(DBSA)1.0 and indirectly by SAXS and TEM in comparison to pure PLH at 165 degrees C, thus indicating plasticization. Glass transitions have not been observed before in polypeptide-surfactant complexes. The present results show that surfactant binding can be a simple scheme to provide steric crowding to stabilize PPII conformation to tune the polypeptide properties, plasticization and flexibility.     

GABA Release Under Normal and Ischemic Conditions

This article overviews the release of GABA in normoxia and ischemia with an emphasis on the mechanisms of the release and on the effects of ionotrophic and metabotropic glutamate receptors, second messengers and nitric oxide on the release.     

Involvement of Metabotropic Glutamate Receptors in Ischemia-Induced Taurine Release in the Developing and Adult Hippocampus

Metabotropic glutamate receptors have recently been envisaged as involved in both potentiation and prevention of ischemic and excitotoxic neuronal damage. The release of the inhibitory amino acid taurine is markedly enhanced in ischemia in both the immature and mature mouse hippocampus. The modulation of [³H]taurine release by metabotropic receptor agonists and antagonists was studied in hippocampal slices from developing (7-day-old) and adult (3-month-old) mice using a superfusion system. Agonists of group I, II and III metabotropic glutamate receptors generally reduced the ischemia-induced release in adult animals. In the immature hippocampus the group I agonists (S)-3,5-dihydroxyphenylglycine and (1±)-1-aminocyclopentane-trans-1,3-dicarboxylate, which mainly enhance neuronal excitation, potentiated initial taurine release in ischemia. Ionotropic glutamate receptor agonists also enhance the ischemia-induced taurine release in developing mice. This glutamate-activated taurine release may thus constitute an important protective mechanism against excitotoxicity in the immature hippocampus.     

Interference of S-Nitrosoglutathione with the Binding of Ligands to Ionotropic Glutamate Receptors in Pig Cerebral Cortical Synaptic Membranes

The interactions of S-nitrosoglutathione (GSNO) with the ionotropic glutamate receptors were studied on synaptic membranes isolated from the pig cerebral cortex. GSNO displaced the binding of [³H]glutamate, 3-[(R)-2-carboxypiperazin-4-yl][³H]propyl-1-phosphonate ([³H]CPP), a competitive N-methyl-D-aspartate (NMDA) antagonist, and [³H]kainate, with IC₅₀ values in the low micromolar range. It failed to displace (S)-5-fluoro-[³H]willardiine, a selective agonist of 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Reduced and oxidized glutathione were almost as effective as GSNO in glutamate and CPP binding. Of the three, GSNO was the most potent in kainate binding. They all stimulated [³H]dizocilpine binding in a concentration-dependent manner. This effect was additive to that of glycine and not mimicked by NO donors such as S-nitroso-N-acetylpenicillamine, 5-amino-3-morpholinyl-1,2,3-oxadiazolium chloride (SIN-1) and nitroglycerin. We assume that GSNO may act as an endogenous ligand at the NMDA and non-NMDA classes of glutamate receptors. In this manner it may facilitate NO transfer and target its delivery to specific sites in these receptors.     

Prevalence of cold-related complaints,symptoms and injuries in the general population: the FINRISK 2002 cold substudy

The prevalence of cold-related complaints and symptoms in the general population has remained unknown. As part of the nationwide FINRISK 2002 health survey performed in Finland, 8,723 people aged 25–64 years filled in a questionnaire asking about the number of hours spent weekly in cold air, their sensations during cold exposure, cold-related complaints, symptoms of diseases, and degradation of performance. Cold thermal sensations at +5°C to −5°C were reported by 35% of men and 46% of women. Almost all subjects reported at least some cold-related complaints, most commonly musculoskeletal pain (men 30%, women 27%), followed by respiratory (25% / 29%), white finger (15% / 18%) and episodic peripheral circulation symptoms (12% / 15%). Decreased mental or physical performance in cold was reported by 75% of men and 70% of women, most commonly impairing manual dexterity and tactile sense. With declining temperature, the first symptom to emerge was pain in the elbow or the forearm (at −3°C), followed by increased excretion of mucus from the lungs (−5°C), while most other symptoms appeared only at lower temperatures of −15°C to −20°C. Most symptoms showed little or no association with the weekly duration of exposure, with the exception of cold-induced pain at most sites. Although, in general, Finns are well adapted to the cold climate, the high prevalence of cold-related complaints poses a challenge to the health care system in terms of decreased performance and the possibility that such symptoms predict more serious health effects, such as increased mortality. This work was carried out in the framework of the FINADAPT project (Assessing the adaptive capacity of the Finnish environment and society under a changing climate).