Yeast CUP1 protects HeLa cells against copper-induced stress

As an essential trace element, copper can be toxic in mammalian cells when present in excess. Metallothioneins (MTs) are small, cysteine-rich proteins that avidly bind copper and thus play an important role in detoxification. Yeast CUP1 is a member of the MT gene family. The aim of this study was to determine whether yeast CUP1 could bind copper effectively and protect cells against copper stress. In this study, CUP1 expression was determined by quantitative real-time PCR, and copper content was detected by inductively coupled plasma mass spectrometry. Production of intracellular reactive oxygen species (ROS) was evaluated using the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay. Cellular viability was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell cycle distribution of CUP1 was analyzed by fluorescence-activated cell sorting. The data indicated that overexpression of yeast CUP1 in HeLa cells played a protective role against copper-induced stress, leading to increased cellular viability (P<0.05) and decreased ROS production (P<0.05). It was also observed that overexpression of yeast CUP1 reduced the percentage of G1 cells and increased the percentage of S cells, which suggested that it contributed to cell viability. We found that overexpression of yeast CUP1 protected HeLa cells against copper stress. These results offer useful data to elucidate the mechanism of the MT gene on copper metabolism in mammalian cells.

Stud male-originating chemosignals: A luteotrophic agent.

The chemosignals from mating male are found to be responsible for protecting his coital partner against pregnancy failure induced by strange male or food-deprivation. The stud male pheromone not only provides luteotrophic support in female of vulnerable condition but also exerts luteotrophic effect in pregnancy-blocked females by inducing pseudopregnancy. The luteotrophic stimulus rendered by stud male to prevent pregnancy failure is mediated through the main olfactory system, and not through the accessory olfactory system, since the accessory olfactory system is primarily involved in perceiving the luteolytic stimulus produced from strange male for causing pregnancy failure. It has been shown that pericopulatory period seems to be crucial in females in the formation of stud male chemosignals, and the olfactory luteotrophic memory of stud male is further proved to be a short-term one. The precise mechanism involved in accessing and retaining the stud male chemical cues is unclear. In this brief review an attempt has been made to bring out the luteotrophic process of stud male chemosignals, the olfactory pathway and critical period to access the signals. The possible neural mechanism and neural chemistry underlying the formation and recognition of mating male chemical cues are also highlighted.

The neurobiology of infant maternal odor learning

Infant rats must learn to identify their mother’s diet-dependent odor. Once learned, maternal odor controls pups’ approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Sexual dimorphism with respect to the macro-morphometric investigations of the forebrain and cerebellum of the grasscutter (Thryonomys swinderianus) / Dimorfismo sexual en relación con la investigación macro-morfométrica del cerebro y cerebelo del grasscutter (Thryonomys swinderianus)

This study was carried out to record the morphometric parameters of the brain of male and female grasscutters. Ten healthy grasscutters (5 males and 5 females) were used in this study. The mean brain weights were 9.80 + 0.50 g and 10.27 + 0.45 g for males and females respectively. The olfactory bulb mean weight was 0.57 + 0.05 g for males and 0.43 + 0.10 g for females. The cerebral and cerebellar mean lengths of 3.14 + 0.04 cm and 1.34 + 0.04 cm for males, 6.26 + 0.10 cm and 3.80 + 0.32 cm for females were observed. The cerebrum, cerebellum and olfactory bulb account for 70%, 12% and 6% of the total brain weight in males and 64%, 13% and 4% in the females respectively. The mean brain lengths were 5.63 + 0.07 cm and 6.26 + 0.1 cm for males and females respectively. There were significant differences in the body and olfactory bulb weights and also, in the whole brain and cerebral lengths between the males and females. In our present research, the ratios of 0.01 for males and 0.006 for females were observed. This suggests a relatively low brain weight in the ruminants. The olfactory bulb in the male is larger than that in the females. Females in turn have longer brain dimension than the males. Cerebellum has no sex variation both in weight and in length.

Este estudio se llevó a cabo para registrar los parámetros morfométricos del cerebro de grasscutters machos y hembras. Diez grasscutters sanos (5 machos y 5 hembras) fueron utilizados en este estudio. La media de peso del cerebro fueron 9,80 +/- 0,50 g y 10,27 +/- 0,45 g para los machos y hembras respectivamente. El peso medio del bulbo olfatorio fue 0,57 +/- 0,05 g para los machos y 0,43 +/- 0,10 g para las hembras. La longitud media del cerebro y del cerebelo fue de 3,14 +/- 0,04 y 1,34 cm +/- 0,04 cm para los machos, y 6,26 +/- 0,10 cm y 3,80 +/- 0,32 cm para las hembras, en las muestras observadas. El cerebro, cerebelo y el bulbo olfatorio representaron un 70%, 12% y el 6% del peso total del cerebro en machos y 64%, 13% y 4% en las hembras, respectivamente. La media de las longitudes del cerebro fueron 5,63 +/- 0,0 y 6,26 cm +/- 0,1 cm para los machos y hembras respectivamente. Hubo diferencias significativas en el peso del cuerpo y el bulbo olfatorio, y también en la longitud total del cerebro de machos y hembras. En nuestra actual investigación, los índices de 0,01 para los machos y de 0,006 para las hembras fueron observados. Esto sugiere un peso relativamente bajo en el cerebro de rumiantes. El bulbo olfatorio en los machos es mayor que en las hembras. A su vez, las hembras presentan una dimensión cerebral mayor que los machos. El cerebelo no tuvo variación según el sexo tanto en peso como en longitud.

Síndrome de Kallmann: uma revisão histórica, clínica e molecular / Kallmann syndrome: a hystorical, clinical and molecular review

A síndrome de Kallmann (SK) é a associação de hipogonadismo hipogonadotrófico (HH) e anosmia descrita por Maestre de San Juan, em 1856, e caracterizada como condição hereditária por Franz Josef Kallmann, em 1944. Muitos aspectos de sua patogenia, variabilidade fenotípica e genotípica foram desvendados nos últimos 15 anos. Conseqüentemente, tem sido difícil manter-se atualizado frente à rapidez que o conhecimento dessa condição é gerado. Nesta revisão, resgatamos aspectos históricos pouco conhecidos sobre a síndrome e seus descobridores; incorporamos novas descobertas relacionadas à embriogênese dos neurônios olfatórios e produtores de GnRH. Esse processo é fundamental para compreender a associação de hipogonadismo e anosmia; descrevemos a heterogeneidade fenotípica e genotípica, incluindo mutações em cinco genes (KAL-1, FGFR1, PROKR2, PROK2 e NELF). Para cada gene, discutimos a função da proteína codificada na migração e maturação dos neurônios olfatórios e GnRH a partir de estudos in vitro e modelos experimentais e descrevemos características clínicas dos portadores dessas mutações.

Kallmann syndrome (KS), the association of hypogonadotropic hypogonadism and anosmia, was described by Maestre de San Juan in 1856 and characterized as a hereditary condition by Franz Josef Kallmann in 1944. Many aspects such as pathogeny, phenotype and genotype in KS were described in the last fifteen years. The knowledge of this condition has grown fast, making it difficult to update. Here we review historical aspects of this condition and its discoverers and describe new findings regarding the embryogenesis of the olfactory bulb and GnRH secreting neuronal tracts that are important for understanding the association of hypogonadism and anosmia. Additionally, we describe the phenotypic and genotypic heterogeneity of KS, including five related genes (KAL-1, FGFR1, PROKR2, PROK2 e NELF), and discuss the function of each codified protein in migration and maturation of the olfactory and GnRH neurons, with data from in vitro and in vivo studies. Finally we describe the clinical phenotype of patients carrying these mutations.

Age and gender-related differences in mitral cells of olfactory bulb

To investigate the age and gender-related differences in mitral cells of the human cadaveric olfactory bulbs. A cross-sectional study. The study was conducted in the Department of Anatomy, University of Health Sciences, Lahore, from August 2005 to July 2007. Sixty olfactory bulbs, 30 each from male and female [age 20-76 years] human cadavers divided into six groups of age and gender-wise were collected from the mortuary of the King Edward Medical University, Lahore. Mitral cells were counted and their diameter was calculated from 10 m thick cresyl violet stained histological sections. Statistical analysis was done using ANOVA for age-related differences and independent t-test for gender-related differences. There was significant reduction in the number of mitral cells and diameter of their nuclei with age. There was significant decrease in the number of mitral cells in males, between groups I and II [p < 0.001]; II and III [p < 0.001]; and I and III [p < 0.001]; statistically significant decrease also occurred in females, between groups IV and V [p < 0.001]; V and VI [p < 0.001]; and IV and VI [p < 0.001]. In most cases, the distance between individual mitral cells was seen to be much greater than in younger group. In group VI, few mitral cells were observed in the cell layer. There was also significant decrease in the diameter of mitral cell nuclei in males, between groups I and III [p < 0.001]; and II and III [p < 0.010]; in females, between groups IV and VI [p < 0.001]; and V and VI [p < 0.001]. No gender-related differences were observed. The number of mitral cells and diameter of their nuclei decreased with advancing age

Simultaneous Single Unit Recording in the Mitral Cell Layer of the Rat Olfactory Bulb under Nasal and Tracheal Breathing

Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell firing pattern within the olfactory bulb (OB). The OB exhibits a significant "ongoing" or spontaneous activity in the absence of sensory stimulation. We characterized this ongoing activity by simultaneously recording several single neurons in the mitral cell layer (MCL) of anesthetized rats and determined the extent of synchrony and oscillations under nasal and tracheal breathing. We recorded 115 neurons and found no significant differences in the mean firing rates between both breathing conditions. Surprisingly, nearly all single units exhibited a long refractory period averaging 14.4 ms during nasal respiration that was not different under tracheal breathing. We found a small incidence (2% of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated firing between adjacent MCL cells. During nasal respiration, a significant oscillation at the respiratory rate was observed in 12% of cells that disappeared during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a long refractory period, probably reflecting the intrinsic OB network properties. Furthermore, in the absence of sensory stimulation, MCL cell discharge does not oscillate in the gamma band and the respiratory cycle can modulate the firing of these cells.

Effect of photic changes and olfactory impairment on reproduction in female south Indian gerbil.

Effect of exposure to constant light (CL), blinding and olfactory bulbectomy (OBX) on reproduction of adult and weanling female Tatera indica cuvieri was investigated. In adult females, CL induced changes in estrus cyclicity. Weanlings subjected to CL showed reduced ovarian weight. Blinding did not bring about changes in estrus cyclicity and reproductive organ weight (ovary and uterus) of either adults or weanlings. Estrus cyclicity of both adults and weanlings were affected consequent to OBX. In weanlings, OBX lowered the ovarian and uterine weight.

Olfactory bulbectomy-induced changes in the reproductive behaviour of the south Indian gerbil, Tatera indica cuvieri.

Male South Indian gerbils (T. indica cuvieri), both adults and weanlings, were olfactory bulbectomized (OBX) and changes in male reproductive behaviour were assessed. Consequent to OBX, majority of the adult males failed to ejaculate, and courtship behaviour has also been considerably reduced. All OBX weanlings were rendered incapable of ejaculation. However, maturational parameters, and organ weights (testes, epididymis and seminal vesicle) remained unchanged in OBX males.

The amygdaloid nucleus and its relationship to epilepsy

El núcleo amigdalino en la base del cerebro, es filogéneticamente la parte más antigua del sistema olfatorio, el cual ha sido recientemente revisado en relación a sus implicaciones en la Epilepsia psicomotora. Su excéresis para el control de las crisis psicomotoras, en algunas ocasiones ha presentado compliaciones como el deterioro de la memoria y alteraciones motoras y sensoriales. La demencia por alcohol y la neurocisticercosis parecen afectar específicamente esta área. El núcleo amigdalino tiene conexiones con el hipocampo y entonces, tiene papel en la memoria. Adicionalmente, tiene conexiones con el hipotálamo y un papel en la expreción de emociones. La indagación patológica se puede hacer mediante estudios de tomografía computada y resonancia magnética

Origin of the telencephalic spindles of the toad Bufo paracnemis

Spindles (8-11 Hz and up to 100 uV in amplitude) recorded on the surface of the surface of the telencephalic hemispheres and olfaactory bulbs of the conscious toad disappear after transection between these two structures, indicating that their presence depends onm the integrity of their interconnections. Spindles continue to be present, although in reduced numbers, after transection between the hemispheres and the diencephalon, indicating that caudal regions are not essential for generating spindles but modulate the neurons responsible for spindle genesis. In contrast, the olfactoryy nerves, in addition to their known phasis activity on the spindles, exert a tonic action since after their section there is a change in the duration and amplitude of component waves

Participación de la dopamina en la motivación / Participation of the dopamine in the motivation

Numerosos experimentos que involucran la estimulación o la lesión de vías dopaminérgicas indican que el fenómeno de la autoestimulación intracerebral depende de la activación de dichas vías. Esta indicación se ha visto reforzada por el hecho de que la aplicación sistémica de fármacos que bloquean o incrementan las acciones sinápticas de la dopamina inducen un decremento y una mejoría, respectivamente, de la conducta de autoestimulación. Sin embargo, estos datos no permiten afirmar que la autoestimulación intracerebral sea debida a la estimulación directa de fibras dopaminérgicas; se decir, esta conducta podría ser debida a la estimulación directa de axones que contienen otros neurotrasnmisores, y que la actividad dopaminérgica represente un eslabón secundario en dicho proceso conductual. Recientemente, estas posibilidades han sido sometidas a pruebas experimentales. Se ha encontrado, en estudios electrofisiológicos, que las características funcionales de las fibras que son directamente activadas durante la autoestimulación difieren de las fibras dopaminérgicas. Por otra parte, se han hecho correlaciones entre la densidad relativa de dopamina de las zonas de autoestimulaciones y las características de ésta (umbrales y frecuencia de respuesta), no existiendo ninguna correlación significativa entre ellas . Estos datos sugieren fuertemente que en la autoestimulación intracerebral no se activan directamente células dopaminérgicas, sino que estas son activadas indirectamente (transinápticamentes)

Representación espacio-temporal dinámica de la información sensorial en el bulbo olfatorio / Dynamic spatio-temporal representation of sensory information in the olfactory bulb

Se estudiaron patrones espacio-temporales de la actividad electroencefalográfica del bulbo olfatorio en conejos crónicamente implantados conmultielectrodos y sometidos a un condicionamiento discriminativo de olores. La utilización de métodos computacionales de análisis espectral espacio-temporal de señales y de técnicas de agrupamiento numérico ha permitido encontrar patrones espaciales de actividad específicos ante la presentación de olores. En base a estos resultados se postula que el bulbo olfatorio opera sobre representaciones de la información sensorial como un sistema dinámico fuera del equilibrio con múltiples estado estables, manifestación de la dinámica de los mecanismos neuronales que determinan el patrón de actividad del bulbo tanto en presencia como en ausencia de estimulación