Biomedical subjects

Isabelle Seif

Publications and source records attributed to Isabelle Seif.

22 records · Page 2Linked to original sources

PubMed2002

Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout mice.

Monoamine oxidase-A knockout (MAO-A KO) mice have elevated brain serotonin (5-HT) and noradrenaline (NA) levels, and one would therefore anticipate increased monoamine release and compensatory changes in other aspects of presynaptic monoamine function. In this study we used voltammetry in brain slices from the locus coeruleus (LC), dorsal raphe (DRN) and striatum (CPu) in 7-week-old MAO-A KO and C3H control mice to measure stimulated monoamine efflux and its control by amine transporters and autoreceptors. In LC, peak NA efflux on stimulation (99 pulses, 100 Hz) was higher in MAO-A KO than C3H mice (938 +/- 58 nm cf. 511 +/- 42 nm; P < 0.001). The NA uptake half time (t(1/2)) was longer in MAO-A KO than in C3H mice (6.0 +/- 0.9 s cf. 1.9 +/- 0.3 s; P < 0.001) and the selective NA reuptake inhibitor desipramine (50 nm) had a smaller effect in MAO-A KO mice. NA transporter binding was significantly lower in the LC of MAO-A KO mice compared to C3H controls (P < 0.01) but not in the DRN. The alpha 2 agonist dexmedetomidine (10 nm) decreased stimulated NA efflux more in C3H than in MAO-A KO mice (73.3% cf. 29.6% inhibition, P < 0.001). In DRN, peak 5-HT efflux on stimulation (99 pulses, 100 Hz) was greater (P < 0.01) in MAO-A KO (262 +/- 44 nm) than C3H mice (157 +/- 16 nm). Moreover, 5-HT uptake t(1/2) was longer (P < 0.05) in MAO-A KO than in C3H mice (8.8 +/- 1.1 s cf. 4.9 +/- 0.6 s, P < 0.05) and the effect of citalopram (75 nm) was attenuated in MAO-A KOs. Serotonin transporter binding was also lower in both the DRN and LC of MAO-A KO mice. The 5-HT(1A) agonist 8-OH-DPAT (1 microm) decreased 5-HT efflux more in C3H than in MAO-A KO mice (38.3% inhibition cf. 21.6%, P < 0.001). In contrast, there were no significant differences between MAO-A KO and C3H mice in CPu dopamine efflux and uptake and the effect of the D(2/3) agonist quinpirole was similar in the two strains. In summary, MAO-A KO mice show major dysregulation of monoaminergic presynaptic mechanisms such as autoreceptor control and transporter kinetics.

Adrenergic Uptake Inhibitors↗

PubMed2002

Enhanced tumor development in mice lacking a functional type I interferon receptor.

The aim of this study was to investigate the contribution of endogenous - that is, without the addition of any interferon (IFN) inducer - type I IFN production in the defense against tumor development. To this purpose, the IFN-alpha receptor (IFNAR) knockout (KO)-induced mutation, resulting in the complete absence of IFN-alpha/beta activity, was introduced into a C3H genetic background by 10 backcross generations, followed by brother-sister matings for at least four generations. The resulting mice were inoculated either with syngeneic C3H melanoma K1735 cells, with allogeneic 3LL carcinoma cells, or with allogeneic B16F10 melanoma cells. With all three tumor cell lines, tumor development and ensuing mortality were enhanced in the IFNAR KO animals. This indicates that endogenous IFN-alpha/beta production is a mediator of natural immunity to tumor development.

Animals↗

PubMed2002

Adult experience-dependent plasticity of S1 barrel cortex in the normal and monoamine oxidase-A knockout (Tg8) mouse.

By restricted use of D2 and D3 whiskers for 3-20 days at maturity (whisker pairing, WP), receptive field plasticity of adult D2 barrel cortex cells was compared in vivo for Tg8 mutant and normal (NOR) mice. Little plasticity was achieved until 20 days of WP in both mice. For Tg8, which lacks segregation of thalamocortical (TC) terminals into barrels, the first relay (TC) responses in layer IV to the principal whisker were potentiated more than in NOR mice by 20 days of WP. In parallel, secondary discharges were reduced more in Tg8 than NOR. It is suggested that both TC excitation and feed-forward inhibition in Tg8 are greater and potentiated more by WP than in NOR mice. Similar differences were reflected in supragranular (SG) cells. For Tg8 but not NOR mice, first latencies of one in five cells in layer IV to an adjacent surround whisker matched those of the principal whisker, increasing to one in three by 20 days of WP experience. Converse decreases occurred for the deprived surround whisker. Changes were similar but smaller for SG cells. Lack of TC segregation in Tg8, therefore, allows substantial overlapping TC terminals of immediate surround whiskers to activate neighbouring D2 column cells directly with potentiated relay to a whisker paired input and weakened relay to a deprived input. Although differing from NOR mice, experiential plasticity was not strongly compromised in Tg8 mice. Differences in WP plasticity from rat barrel cortex are discussed.

Animals↗

PubMed1999

Knockout Corner: Knockout mice for monoamine oxidase A.

A line of transgenic mice was isolated in which transgene integration had caused a deletion in the gene encoding monoamine oxidase A, an enzyme that degrades serotonin and norepinephrine. This has provided an animal model of MAOA deficiency in humans, a condition characterized by borderline mental retardation and impulsive aggression.

Journal Article↗