Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.     

Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings

Fingerprinting of more than 700 clinical and environmental isolates of Aspergillus fumigatus from four differential hospital settings was undertaken with a dispersed repeated DNA sequence. The analysis of the environmental isolates showed that the airborne A. fumigatus population is extremely diverse, with 85% of the strains being represented as a single genotype isolated once. The remaining 15% of the strains were isolated several times and were able to persist for several months in the same hospital environment. No strains were found to be associated with a specific location inside the hospital, and identical strains were isolated from different buildings of the hospital and outdoors. Isolation of the same strain both from patients and from the environment of the same hospital is highly suggestive of a nosocomial infection. The characteristics of the environmental fungal population explains the two main results obtained from the typing of the clinical isolates: (i) the absence of a common strain responsible for an invasive aspergillosis outbreak results from the extreme diversity of the environmental population of A. fumigatus in contact with the patients, and (ii) patients hospitalized in different wards of the same hospital can be infected with the same strain since every patient might inhale the same spore population.     

Phase 1B ventricular arrhythmia in the dog: localized reentry within the mid-myocardium

Our aim was to investigate the relationships between defensiveness and repression, on the one hand, and self-reported stressor exposure and resting blood pressure, on the other hand. In addition, different operationalizations of defensiveness and repression were compared. Participants were 310 male and 90 female employees representing a wide range of occupations. Before a medical examination, all subjects completed questionnaires measuring defensiveness, anxiety, repression, daily hassles, and life events. After controlling for potentially confounding variables, multiple regression analyses revealed an inverse association between defensiveness and self-reported number of daily hassles and a positive link between defensiveness and resting systolic blood pressure. In general, the interaction between defensiveness and anxiety (representing repression) did not add to the predictive power of defensiveness and anxiety alone. The results support the notion that defensive individuals tend to underreport problems, while exhibiting elevated resting blood pressures.