Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Cell‐adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain‐specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age‐/gender‐matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell‐adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD.     

Reciprocal changes in amino acid metabolism in mammary gland and liver of the lactating rat on starvation and refeeding as indicated by the tissue accumulation of alpha-amino[1-14C]isobutyrate.

Measurements of the tissue accumulation in vivo and in vitro by hepatocytes and mammary-gland acini of alpha-amino[1-14C]isobutyrate ([1-14C]AIB) were compared in virgin and lactating rats. The results indicate the existence of a reciprocal relationship between mammary gland and liver for AIB accumulation that is dependent on the lactational and the nutritional state of the rat. This suggests that amino acids are preferentially directed to the mammary gland during active lactation.     

Evidence that use of Triton WR1339 underestimates the triacylglycerol entry rate into the plasma of lactating rats owing to continued accumulation of lipid in the mammary gland.

An analysis is presented of the catalytic factors responsible for the rate-enhancement that may be observed when a protein modification reaction is compared with a reaction of the same modifying agent with a model micromolecular compound exhibiting the same reactive group as the protein under study. It is seen that affinity-mediated rate-enhancement of protein modification is realized by the loss of activation entropy. On the assumption that attainment of maximal affinity-mediated rate-enhancement presents with an activation entropy of the protein modification reaction equal to zero, whereas the activation enthalpy of the reaction remains unchanged, it is shown that the value for maximal affinity-mediated rate-enhancement is equal to e-delta s++/R. Accordingly, protein modification reactions may be differentiated into (i) reactions the rate-enhancement of which (relative to the reaction of the same modifying agent with a model compound) is primarily entropy-controlled and (ii) reactions the rate-enhancement of which is primarily enthalpy-controlled. It is seen that modifying agents of low reactivity towards model compounds, but with a high, i.e. highly negative, activation entropy are better suited as prospective affinity-based protein-modifying agents, since the potential affinity-mediated rate-enhancement, and hence the selectivity, of these compounds is necessarily high. Kinetic and thermodynamic constants of the reaction of modifying agents with proteins, and with model compounds, and values of maximal affinity-mediated rate-enhancement, based on published data of the reaction of several modifying agents with model compounds, are presented and discussed.     

Physiological significance of altered insulin metabolism in the conscious rat during lactation.

Uptake of radioactively labelled insulin by the mammary gland of the rat increased 12-fold in lactation compared with non-lactating controls. This uptake was decreased by the presence of unlabelled insulin, indicating that it occurred via insulin receptors. The plasma half-life of insulin is decreased in lactation from 9.4 min to 4.8 min, and the metabolic clearance rate for insulin increased from 7.26 to 13.03 ml/kg body wt. per min. The basal insulin and glucose concentrations in the plasma were decreased in lactation. Infusion of insulin at a dose which led to a small physiological rise in plasma insulin concentration increased lipogenic rates in the mammary gland by 100% without causing marked hypoglycaemia. It is concluded that the lactating mammary gland is a highly insulin-sensitive tissue and that the lower plasma insulin during lactation occurs primarily as a result of this sensitivity increasing extraction of glucose by the gland and thus producing a decrease in the plasma glucose concentration. It is suggested that a secondary result of the fall in plasma insulin concentration is the preferential direction of substrates (glucose and non-esterified fatty acids) towards the lactating mammary gland and away from adipose tissue and the liver.     

Sulfated polysaccharides inhibit the catabolism and loss of both large and small proteoglycans in explant cultures of tendon

This study investigated the effects of two highly sulfated polysaccharides, calcium pentosan polysulfate and heparin, on the loss of newly synthesized proteoglycans from the matrix of explant cultures of bovine tendon. The tensional region of deep flexor tendon was incubated with [35S]sulfate for 6 h and then placed in culture for up to 15 days. The amount of radiolabel associated with proteoglycans lost to the medium and retained in the matrix was determined for each day in culture. It was shown that both sulfated polysaccharides at concentrations of 1000 microg x mL(-1) inhibited the loss of 35S-labeled large and small proteoglycans from the matrix and concomitant with this was a retention of chemical levels of proteoglycans in the explant cultures. In other explant cultures that were maintained in culture in the presence of both agents for more than 5 days after incubation with [35S]sulfate, inhibition of the intracellular catabolic pathway was evident, indicating that these highly sulfated polysaccharides also interfered with the intracellular uptake of small proteoglycans by tendon cells.     

Plants and human health in the twenty-first century

The concept of growing crops for health rather than for food or fiber is slowly changing plant biotechnology and medicine. Rediscovery of the connection between plants and health is responsible for launching a new generation of botanical therapeutics that include plant-derived pharmaceuticals, multicomponent botanical drugs, dietary supplements, functional foods and plant-produced recombinant proteins. Many of these products will soon complement conventional pharmaceuticals in the treatment, prevention and diagnosis of diseases, while at the same time adding value to agriculture. Such complementation can be accelerated by developing better tools for the efficient exploration of diverse and mutually interacting arrays of phytochemicals and for the manipulation of the plant's ability to synthesize natural products and complex proteins. This review discusses the history, future, scientific background and regulatory issues related to botanical therapeutics.     

Development of a topographically organized auditory network in slice culture is calcium dependent

Inhibitory and excitatory connections of remarkably precise topographic order are characteristic features of the mammalian auditory system, particularly within the superior olivary complex (SOC). Little is known about the requirements for the correct development of these specific connections. Previous in vivo experiments have demonstrated a high expression of calcium-binding proteins in this system during development, pointing to the need for precise calcium regulation. Here, we have employed an organotypic slice culture from the above neuronal network and analyzed the requirements for the maintenance and development of this system in vitro. When slices from neonatal rats were incubated in standard culture medium for up to 7 days, we found no organotypic features. Only if 25 mM KCl was added to the culture medium, the cytoarchitecture of the nuclei, the neuronal morphology, and the specificity and topography of internuclear connections were indistinguishable from that in vivo. The addition of calcium channel blockers (MgCl₂ and nifedipine) to the high-KCl medium reduced organotypicity drastically, indicating that a depolarization-induced increase of intracellular calcium is indispensable. Furthermore, the temporal course of the expression of the calcium-binding protein parvalbumin in culture under high KCl mimics that in vivo, demonstrating developmental processes during incubation. The need for calcium influx into neurons of this auditory network in vitro (which is not seen in other slice culture systems) strengthens the hypothesis that an optimal calcium concentration is exceptionally important in auditory neurons. The effect of KCl in the slice cultures may substitute for input activity regulating intracellular calcium in auditory neurons in vivo. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 97–112, 1998