The Role of the δ GABA(A) Receptor in Ovarian Cycle-Linked Changes in Hippocampus-Dependent Learning and Memory

The δ subunit of the GABA_AR is highly expressed in the dentate gyrus of the hippocampus where it mediates a tonic extrasynaptic inhibitory current that is sensitive to neurosteroids. In female mice, the expression level of the δ subunit within the dentate gyrus is elevated in the diestrous relative to estrous phase of the estrous cycle. Previous work in our lab found that female δ-GABA_AR KO mice showed enhanced hippocampus-dependent trace but normal hippocampus-independent delay fear conditioning. Wild-type females in this study showed a wide range of freezing levels, whereas δ-GABA_AR KO mice expressed only high levels of fear. We hypothesized that the variability in the wild-type mice may have been due to estrous cycle-mediated changes in the expression of the δ-GABA_AR, with low levels of freezing in mice that were in the diestrous phase when dentate gyrus tonic inhibition is high. In the present study we tested this hypothesis by utilizing contextual, delay, and trace fear conditioning protocols in mice that were trained and tested in either the diestrous or estrous phases. Consistent with our hypothesis, we found a significant impairment of hippocampus-dependent learning and memory during diestrus relative to estrus in wild-type mice and this impairment was absent in δ-GABA_AR mice. These findings argue that the δ-GABA_AR plays an important role in estrous cycle-mediated fluctuations in hippocampus-dependent learning and memory.     

Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice.

The immediate responses of the upper respiratory tract (URT) to the irritants acrolein and acetic acid were examined in healthy and allergic airway-diseased C57Bl/6J mice. Acrolein (1.1 ppm) and acetic acid (330 ppm) vapors induced an immediate increase in flow resistance, as measured in the surgically isolated URT of urethane-anesthetized healthy animals. Acrolein, but not acetic acid, induced a small URT vasodilatory response. In awake spontaneously breathing mice, both vapors induced a prolonged pause at the start of expiration (a response mediated via stimulation of nasal trigeminal nerves) and an increase in total respiratory specific airway flow resistance, the magnitude of which was similar to that observed in the isolated URT. Both responses were significantly reduced in animals pretreated with large doses of capsaicin to defunctionalize sensory nerves, strongly suggesting a role for sensory nerves in development of these responses. The breathing pattern and/or obstructive responses were enhanced in mice with ovalbumin-induced allergic airway disease. These results suggest that the primary responses to acrolein and acetic acid vapors are altered breathing patterns and airway obstruction, that sensory nerves play an important role in these responses, and that these responses are enhanced in animals with allergic airway disease.     

Gross anatomy of the gastrointestinal system of harp seals (Phoca groenlandica)

The gross anatomy of the gastrointestinal system of 12 harp seals ( Phoca groenlandica ) was investigated. Harp seals have a typical carnivore monogastric stomach. The tissue wet weight of the stomach of harp seals represented 27.01 (S.D. 3.99)% ( n = 12) of the total gastrointestinal tract (GI-tract). All animals were killed while resting on the ice, and had empty stomachs, but when expanded with water to a 30cm pressure the stomach contained 0.60 to 1.60 litres, representing 1.00 (S.D. 0.26)% ( n = 12) of the body mass. The small intestine ranged in length from 20.44 to 25.32m, being 14.36 (S.D. 1.58) times the body length, and the tissue wet weight constituted 67.61 (S.D. 4.55)% of the total GI-tract ( n = 12). Both caecum and colon were short, maximally 5 and 78 cm, respectively, being 0.022 (S.D. 0.005) and 0.38 (S.D. 0.06) times the body length ( n = 12). The caecum tissue wet weight was only 0.18 (S.D. 0.04)% of the total GI-tract weight, while the colon tissue wet weight contributed to 5.33 (S.D. 1.19)% ( n = 12). It is concluded that harp seals have relatively long intestines compared to minke whales eating a comparable diet in the North Atlantic Ocean.     

Photoaffinity labeling of three renal cyclic 3′,5′-adenosine monophosphate-binding proteins

Evidence is presented for the presence of multiple cyclic AMP binding components in the plasma membrane and cytosol fractions of porcine renal cortex and medulla. N⁶-(Ethyl-2-diazomalonyl)-3′,5′-adenosine monophosphate, a photoaffinity label for cyclic AMP binding sites, exhibits non-covalent binding characteristics similar to cyclic AMP in membrane and soluble fractions. Binding data for either compound to the plasma membrane fraction yields biphasic Scatchard plots while triphasic plots are obtained with the dialyzed cytosol. When covalently labeled fractions are separated on SDS-polyacrylamide gel electrophoresis, the cyclic AMP photoaffinity label is found on 49 000 and 130 000 dalton components in each kidney fraction. DEAE-cellulose and gel filtration chromatography of the labeled cortical cytosol fraction establishes that the three components suggested by the binding data correspond to two 49 000 dalton species and a 130 000 component. The 49 000 species have higher affinities for cyclic AMP than the 130 000 component (K_a(1) = 2.0 · 10⁹, K_a(2) = 1.7 · 10⁸, K_a(3) = 1.0 · 10⁷). The 49 000 components are associated with protein kinase activity while the 130 000 component does not exhibit protein kinase, adenosine deaminase, or cyclic nucleotide phosphodiesterase activity. Immunologic results and effects of phosphorylation and cyclic GMP on cyclic AMP binding further suggest that the 49 000 components are regulatory subunits of cyclic AMP-dependent protein kinases. Cyclic AMP binding to the 130 000 component is markedly inhibited by adenosine and adenine nucleotides, but not cyclic GMP. Thus, this component may reflect an aspect of adenosine control or metabolism which may or may not be a cyclic AMP-related cellular function.     

Plasma growth hormone response to synthetic GH-RH1-44 in 52 children and adults with growth hormone deficiency of various etiologies

52 patients (42 children and 10 adults) with growth hormone deficiency (GHD), grouped into four diagnostic categories, and 6 children with constitutional short stature who served as controls were tested for plasma GH response to synthetic GH-RH1-44 given in an intravenous bolus. The response was classified into three degrees according to the magnitude of the maximal rise: Good, greater than 9 ng/ml; Partial, 3.1-9.0 ng/ml; None, less than or equal to 3 ng/ml. Among the GHD patients the highest response was observed in patients with partial growth hormone deficiency (PGHD), and 60% of the children with isolated GH deficiency (IGHD) showed an increase in plasma GH levels. Nevertheless, the response of the GHD patients was lower than that in the control group. In the children and adolescents with PGHD and IGHD the response was not age related. Among those with multiple pituitary hormone deficiencies-idiopathic (MPHD-ID) there was no response in the adolescents although a hypothalamic disorder had been documented by other tests. Among those with MPHD-organic (MPHD-ORG) the GH-RH stimulated GH secretion in the patients with glioma, who had received only irradiation treatment, and in the youngest of the patients with craniopharyngioma. Of the 10 young adults tested none showed a good response. It is concluded that GH-RH is useful in differentiating between GH deficiency of hypothalamic origin and that of pituitary origin, and in selecting those patients who might benefit from long-term treatment with GH-RH in the future.     

Seasonal Dynamics of Atlantic Herring (Clupea harengus L.) Populations Spawning in the Vicinity of Marginal Habitats

Gillnet sampling and analyses of otolith shape, vertebral count and growth indicated the presence of three putative Atlantic herring (Clupea harengus L.) populations mixing together over the spawning season February–June inside and outside an inland brackish water lake (Landvikvannet) in southern Norway. Peak spawning of oceanic Norwegian spring spawners and coastal Skagerrak spring spawners occurred in March–April with small proportions of spawners entering the lake. In comparison, spawning of Landvik herring peaked in May–June with high proportions found inside the lake, which could be explained by local adaptations to the environmental conditions and seasonal changes of this marginal habitat. The 1.85 km² lake was characterized by oxygen depletion occurring between 2.5 and 5 m depth between March and June. This was followed by changes in salinity from 1–7‰ in the 0–1 m surface layer to levels of 20–25‰ deeper than 10 m. In comparison, outside the 3 km long narrow channel connecting the lake with the neighboring fjord, no anoxic conditions were found. Here salinity in the surface layer increased over the season from 10 to 25‰, whereas deeper than 5 m it was stable at around 35‰. Temperature at 0–5 m depth increased significantly over the season in both habitats, from 7 to 14°C outside and 5 to 17°C inside the lake. Despite differences in peak spawning and utilization of the lake habitat between the three putative populations, there was an apparent temporal and spatial overlap in spawning stages suggesting potential interbreeding in accordance with the metapopulation concept.