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Biomedical subjects

J Kume-Kick

Publications and source records attributed to J Kume-Kick.

7 recordsLinked to original sources
PubMed2001

Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake.

Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (alpha) and tortuosity (lambda), together with linear uptake (k'), were determined for tetramethylammonium (TMA(+)), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA(+)-diffusion measurements revealed a large alpha of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for lambda and k' for TMA(+) were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k' for DA in SNc and VTA (0.08--0.09 s(-1)) than in SNr (0.006 s(-1)), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 microm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.

Animals↗
PubMed1998

Dependence of dopamine calibration factors on media Ca2+ and Mg2+ at carbon-fiber microelectrodes used with fast-scan cyclic voltammetry.

Carbon-fiber microelectrodes and voltammetric methods have been used extensively for the detection of dopamine in brain tissue in vivo and in vitro. Voltammetric microelectrodes are often calibrated in non-physiological media, like phosphate-buffered saline, rather than in oxygenated physiological media. Here, we determined dopamine calibration factors (nA microM-1) in several defined solutions for two types of carbon-fiber electrode used with fast-scan cyclic voltammetry. For both electrode types, dopamine calibration factors, and thus electrode sensitivities, were 2-3-fold higher in phosphate- or HEPES-buffered saline than in a bicarbonate-based artificial CSF (ACSF) that reflected that normal ionic composition of brain extracellular fluid. Removal of Ca2+ and Mg2+ from ACSF eliminated this difference. Because extracellular Ca2+ concentration ([Ca2+]o) can fall under stimulation conditions used to elicit dopamine release, we also evaluated the size of stimulated [Ca2+]o shifts in guinea pig midbrain slices using ion-selective microelectrodes. The [Ca2+]o decreases were less than 100 microM, which was well below the mM decreases observed to alter DA sensitivity. Consequently, calibration data obtained in normal physiological solutions should be valid under conditions of mild stimulation. Moreover, calibration in divalent cation-free media will cause calculated DA levels to be underestimated and should be avoided, unless appropriate for a given experimental paradigm.

Animals↗
PubMed1998

Estrogen-dependent modulation of rat brain ascorbate levels and ischemia-induced ascorbate loss.

Brain ascorbate levels in young adult female rat are lower than those in males. Loss of ascorbate during ischemia is also less in females, suggesting lower oxidative stress. After ovariectomy, however, ischemia-induced loss equals that in males. In the present study, we determined ascorbate levels in maturing male and female rat brain to establish when the gender difference in content arises. We further investigated whether 17beta-estradiol and/or progesterone treatment modulate levels and ischemia-induced loss in ovariectomized females and compared these data with those from normal females in proestrus and estrus. Gender differences in brain ascorbate content were absent before puberty and persisted only in cortex in aging rats. Chronic estradiol treatment, whether alone or in combination with progesterone, prevented an ovariectomy-induced ascorbate increase in hippocampus and caused levels in cortex and cerebellum to fall below those of randomly sampled normal females. These same low levels were found during proestrus and estrus. Estradiol replacement after ovariectomy prevented enhanced ischemia-induced ascorbate loss in hippocampus, but not in cortex or cerebellum. Ischemia-induced losses in proestrus and estrus were similar to those in normal controls. Progesterone had little effect in any region. These data indicate that ascorbate content and redox balance in female brain are influenced postpubertally by estrogens in a region-selective manner.

Age Factors↗
PubMed1996

Enhanced oxidative stress in female rat brain after gonadectomy.

Oxidative stress, assessed by tissue ascorbate loss following ischemia, is greater in male than female rat brain. The factors mediating this gender difference are unclear. The goal of the present studies was to determine the influence of gonadal sex hormones on this difference. Three weeks prior to experiment, adult Long-Evans male and female rats were gonadectomized for comparison with controls. Ascorbate and glutathione levels were determined in brain and plasma under basal conditions and in brain after one-hour decapitation ischemia, using liquid chromatography with electrochemical detection. Basal ascorbate levels in brain were 6-9% higher in males than in females, whereas plasma levels were 100% higher in males. After gonadectomy, the gender difference in plasma ascorbate levels was lost, while the effect on basal brain levels depended upon region. Ischemia-induced losses in brain ascorbate were three-fold greater in control males compared to control females. Significant losses occurred in frontal cortex, hippocampus, and cerebellum in males during ischemia, whereas loss in females was significant in cerebellum only. After gonadectomy, increased ascorbate loss was seen in all female brain regions, indicating enhanced oxidative stress. This increase eliminated the gender difference in loss; male ascorbate loss was comparatively unaffected by gonadectomy. Glutathione levels and loss were unaffected by either gender or gonadectomy, indicating differences in regulation from that of ascorbate. These findings provide evidence for the hypothesis that protection against oxidative stress is afforded by ovarian sex hormones, thus decreasing the potential for oxidative cell damage in females compared to males.

Animals↗
PubMed1995

Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia.

Ascorbate and glutathione (GSH) are the primary water-soluble antioxidants in the CNS. Oxidative stress, sometimes indicated by loss of these antioxidants, has been linked to several clinical and experimental conditions, including cerebral ischemia. These conditions are also gender-linked, with greater incidence or severity in males than females. To test whether there are gender differences in oxidant/antioxidant regulation, we determined basal levels of ascorbate and GSH in rat brain and their loss after 1 h decapitation ischemia. We found that ascorbate levels in male rat brain were 7-10% higher than in females, depending on region, whereas GSH levels were gender-independent. Significant ascorbate loss (up to 12%) occurred in males during ischemia, with a regional pattern of cerebellum > hippocampus > prefrontal cortex. Loss of ascorbate in females was not significant in any region. By contrast, loss of GSH was significant in both males and females. Greater loss of GSH than ascorbate was in agreement with previous studies and was consistent with loss from enzymatic degradation, as well as oxidation. The significant gender difference in ascorbate loss, as a marker of oxidative stress, supports the hypothesis that inherent differences in oxidant/antioxidant regulation contribute to gender differences in response to ischemia and other pathological conditions.

Analysis of Variance↗
PubMed1994

Sex hormones affect muscle contractility and motor functional recovery following peroneal nerve crush.

This study was performed to investigate possible sex differences in the contractile responses of the reinnervated extensor digitorum longus (EDL) muscle. Electromechanical studies on muscle stimulated indirectly through its nerve provided information on muscle contractility during early reinnervation. Locomotor functional recovery was followed by analyzing changes in footprint parameters over time. At 9 days postsurgery, nerve crush affected negatively many isometric contractile parameters, including twitch peak rate and contraction amplitude, as well as tetanic peak rate, contraction amplitude, and half relaxation time (HRT), regardless of sex. Female EDLs had a greater tetanic peak contraction amplitude and fully recovered twitch HRT levels. While this sex difference is clearly apparent in muscle contractility, it was abolished when considering motor functional recovery. Locomotor tests were less sensitive in demonstrating sex differences during recovery from nerve crush. Peroneal functional index (PFI), a parameter well-described by Bain in 1989, is a paradigm which compares all footprint changes incurred in a rat after peroneal nerve crush, using data obtained from uncrushed side to normalize values. PFI indicated that removal of the sex steroids seriously hindered recovery of motor function regardless of gender.

Adrenocorticotropic Hormone↗