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Distribution of beta-amyloid and amyloid precursor protein in the brain of spawning (senescent) salmon: a natural, brain-aging model.

Brain amyloid precursor protein (APP), a normal constituent of neurons, glial cells and cerebrospinal fluid, has several proposed functions (e.g., in neuronal growth and survival). It appears, however, that altered processing of APP is an initial or downstream step in the neuropathology of brain aging, Alzheimer's disease (AD), and Down's syndrome (DS). Some studies suggest that proteolytic cleavage of APP, producing beta-amyloid (Abeta(1-42)), could have neurotoxic or neuroprotective effects. In this study, we utilized antibodies to human APP(695) and Abeta(1-42,) and Congo red staining, to search for amyloid deposition in the brain of semelparous spawning kokanee salmon (Oncorhynchus nerka kennerlyi). Intracellular APP(695) immunoreactivity (APP-ir) was observed in brain regions involved in gustation (glomerulosus complex), olfaction (putative hippocampus, olfactory bulb), vision (optic tectum), the stress response (nucleus preopticus and nucleus lateralis tuberis), reproductive behavior (nucleus preopticus magnocellularis, nucleus preopticus periventricularis, ventral telencephalon), and coordination (cerebellum). Intra- and extra-neuronal Abeta(1-42) immunoreactivity (Abeta-ir) were present in all APP-ir regions except the nucleus lateralis tuberis and Purkinje cells of the cerebellum (coordination). Thus, the relationship between APP and Abeta deposition during brain aging could shed light on the processing of APP into Abeta, neurodegeneration, and possible protection of neurons that are functioning in spawning but senescent salmon. Pacific salmon, with their predictable and synchronized life history, could provide research options not available with the existing models for studies of brain aging and amyloidosis.

Aging↗

Gradations of emulation learning in infants' imitation of actions on objects.

This study explored different gradations of emulation in the imitation of actions on objects by 17-month-olds. Experiment 1 established levels of behavioral reproduction following prerecorded video demonstrations similar to those levels following live demonstrations. In Experiment 2, two digitally modified videos, where object movements or body movements critical to producing the target action were highlighted in isolation, were developed. Infants produced the target action equally frequently by observing the object movement video and observing the unmodified video. In contrast, their performance was much less successful based on the body movement video. In Experiment 3, the performance obtained following the object movement video was similar to that following a further video that emphasized the object movements produced in unsuccessful attempts to produce the target action. These findings suggest that emulation in the form of object movement reenactment or affordance learning plays a role in the social learning of actions on objects during infancy.

Attention↗

Chemical senses.

In the last decade, studies using approaches from molecular biology have substantially advanced our understanding of the early events in olfaction and taste. The many odorants that we can recognize may well interact with many distinct receptor proteins. Of the four taste qualities that we recognize, studies on salty and sour suggest that these tastes involve ion channels in the membrane of receptor cells while sweets and bitters bind to receptor proteins. Some volatiles (pheromones) play special roles in reproductive behavior via the vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that humans lack a VNO has been questioned recently, thus raising the fascinating possibility of human pheromones. The roles that taste and smell play in the world of the newborn are very different. Acceptance of sweet and rejection of bitter appear to be hard-wired while the affect associated with odors depends much more on experience. Genetic variation may produce total losses (Kallman's syndrome produces anosmia and familial dysautonomia produces ageusia) or losses specific to certain stimuli. The best known of the specific anosmias is that for androstenone, which has no smell to some, a urinous smell to others, and a smell like sandalwood to still others. Analogous to the specific anosmias, some individuals are unable to taste PROP while others, supertasters, perceive PROP to be exceedingly bitter. Clinical studies reveal pathologies responsible for total or partial losses. The olfactory system, dependent on one cranial nerve, is more vulnerable than taste, and total anosmia is a relatively common clinical problem. Three cranial nerves carry taste and two of those nerves inhibit one another such that damage to one disinhibits the other and preserves over-all taste function. Total ageusia is very rare. Throughout these studies we see that taste and olfaction have different properties and often different functions (e.g. odor and reproduction). Yet taste and smell can also be integrated to determine what does or does not enter the body. In Adrian's words, "we are dealing with the sense organs which signal the quality of the air we breathe and that of the food and drink we propose to swallow."

Ageusia↗

Alterations in the estrogen sensitivity of hypothalamic proenkephalin mRNA expression with age and prenatal exposure to alcohol.

Studies suggest that exposure to alcohol in utero causes reproductive and neuroendocrine deficits in adult female rats. The ventromedial nucleus of the hypothalamus (VMN) is an estrogen-sensitive brain region which is regarded as a primary locus for modulating female reproduction. Proenkephalin (PE) mRNA expression in the VMN is dramatically increased by estrogen and this elevation is thought to be involved in modulating female reproductive behavior and neuroendocrine function. To examine whether prenatal alcohol exposure has long-term effects on the ability of estrogen to influence hypothalamic PE mRNA levels, female rats at 2-3, 6-7 or 15-18 months of age, derived from alcohol- or control-fed dams, were studied. 7 days following ovariectomy, animals received either estrogen or sham treatment for 2 days prior to sacrifice. PE mRNA levels in the VMN and striatum were determined by in situ hybridization histochemistry. Film autoradiogram density, numbers of PE mRNA-expressing cells and exposed silver grains/cell were analyzed. Estrogen treatment increased hybridization density, the number of PE mRNA-expressing cells and PE mRNA (grains) level/cell in the VMN of normal adult female rats. In old rats, estrogen increased the number of PE mRNA-expressing cells without up-regulating PE mRNA grain density/cell. In fetal alcohol-exposed (FAE) female rats, the number of cells that expressed PE mRNA did not increase following estrogen treatment at any age. Elevation of grain density/cell following estrogen was observed in FAE animals but only at 7-8 months of age. Overall, these data indicate that the estrogen responsiveness of PE mRNA expression in the VMN declines with age and, furthermore, prenatal exposure to alcohol blunts estrogen's effects on PE mRNA expression in the adult VMN. These finding may help to explain the mechanisms underlying the loss of reproductive function observed in FAE females.

Age Factors↗

Barrier and spermicidal contraceptive methods and risk of invasive cervical cancer.

The effects of barrier and spermicidal methods of contraception on cervical cancer risk were examined by studying 479 cases of histologically confirmed invasive cervical cancer cases and 788 random digit dialing controls. In addition to a detailed history of contraceptive practices, information was available on numerous potential confounders, including demographic characteristics, sexual behavior, reproductive factors, Pap smear screening history, and smoking. After adjustment for relevant confounders, diaphragm and condom use were found not to be significantly associated with risk of cervical cancer. Although there was a small reduction in risk (OR = 0.8) associated with long-term use (5+ years) of the diaphragm, the effect appeared to relate to concomitant spermicide use, since there was evidence of further decreases in risk for women using spermicides alone for extended periods (OR = 0.7 for 5+ years). Effects were only seen among subjects of higher income and education levels, suggesting that patterns of usage may be important. The potential ability of spermicides to reduce cervical cancer risk by neutralizing viral agents warrants further attention.

Adult↗

Reproductive activity of Pelibuey and Suffolk ewes at 19 degrees north latitude.

Under photoperiod regulated conditions, some Pelibuey ewes appear to express estrous cycles continuously throughout the year. Ovulatory activity of Suffolk ewes has not being determined at 19 degrees N. The aim of the present study was to describe the annual reproductive cycle of Pelibuey and Suffolk ewes under natural conditions at 19 degrees N. Ten adult ewes of each breed were maintained under natural environmental conditions, on a constant plane of nutrition and isolated from rams. The ovulatory activity of both breeds was monitored over 2 years (2003 and 2004) by quantifying progesterone concentrations in blood samples taken twice a week. For both breeds, the proportion of ovulating ewes per month and year was analyzed by chi(2). The duration of anestrus was compared between breeds and years by analysis of variance. Correlation of ambient temperature and weight changes with the ovulatory activity was evaluated by regression procedure. Ovulatory activity was different (P<0.05) between breeds from February to July. Pelibuey sheep (60%, 6 of 10) ovulated continuously during the entire study; one animal was eliminated in the second year, due to ovarian follicular cysts and three ewes had anestrous periods from 65+/-46 to 70+/-36 days. Suffolk ewes displayed reproductive seasonality similar to that observed in sheep of the same breed in latitudes greater than 35 degrees . Within breed, reproductive behavior of sheep was similar between years, with the only difference (P<0.05) observed in February for Pelibuey and in July for Suffolk relative to other months. Ambient temperature was not correlated with ovulatory activity. The body weight of Pelibuey ewes was constant during the entire study and was not correlated with ovulatory activity. There was, however, an increase on the body weight of Suffolk ewes, but this variation was not related to ovulatory activity. These findings lead to the conclusion that at 19 degrees N, a high proportion of Pelibuey ewes is capable of ovulating throughout the year, whereas Suffolk ewes undergo seasonal anestrous periods similar to those observed in individuals of the same breed at latitudes greater than 35 degrees . Identification of continuous ovulatory Pelibuey ewes may be the first step for developing a selection program against seasonality to increase lambing frequency.

Animals↗

Glucoprivic regulation of estrous cycles in the rat.

Previous research has shown that glucoprivation induced by chronic 2-deoxy-D-glucose (2DG) treatment extends estrous cycle length and disrupts reproductive behaviors in female hamsters, similar to food deprivation. Such treatment also suppresses food intake, which is reversed in male rats by reducing brain histamine levels prior to 2DG treatment. We, therefore, determined if 2DG extends estrous cycles in the female rat and if this is due to elevated brain histamine levels. We measured estrous cycle length during 2DG-induced glucoprivation, in the presence and absence of alpha-fluoromethylhistidine (FMH), a treatment that reduces brain histamine levels. Adult female rats were treated for 72 h with either saline (n = 8), 2DG (200 mg/kg S.C. every 6 h; n = 9), or FMH (100 mg/kg i.p. daily) + 2DG (200 mg/kg; n = 7). An additional group was treated with FMH (100 mg/kg i.p.; n = 5) alone. To determine if 2DG extends estrous cycles due to glucoprivation or to decreased caloric intake, a group of rats (n = 7) received a reduced diet equal to the mean daily food intake of rats receiving 2DG alone. 2DG induced more long estrous cycles compared to rats receiving saline, FMH + 2DG, or FMH alone. In rats treated with FMH + 2DG, the percentage of 4-5-day cycles was similar to that of saline-treated rats, and a high percentage of 4-5-day cycles was also observed in rats receiving a reduced diet. These data suggest that 2DG does not suppress estrous cycles through a decrease in total calorie intake, but rather by inducing glucoprivation. In addition, during 2DG-induced glucoprivation, elevated brain histamine levels contribute to the mechanism that suppresses reproductive function.

Animals↗

Use of oral contraception in the United States, 1965. In only 5 years oral contraception has become a major means of regulating fertility.

This is the first report from the Na-tional Fertility Study, 1965, a survey of the reproductive behavior of a national sample of married women, under the age of 55, living with their husbands. The report presents basic data on the use of oral contraception by women under the age of 45, in relation to age, parity, education, race, and religion. The study leads to certain conclusions, as follows. Present, past, and prospective use vary inversely with the age of the woman and directly with the number of years of schooling; the majority of young women with college training have already used the oral contraceptive. Use by Negroes is somewhat less extensive than use by whites, particularly for ages below 25; some of this difference is explainable by concomitant racial differences in educational level. Negroes seem less likely than whites to use oral contraception for timing early births, and more likely, when they do use it, to be attempting to terminate their fertility. The same observation holds for white Catholics in relation to white non-Catholics. Although the extent of use may be lower among Catholics than non-Catholics, the proportion of Catholics who report use is substantial indeed in view of the persisting theological controversy. The prospects for increased use of oral contraception seem very good at present, but they may be limited by further developments in the technology of fertility regulation. Meanwhile the birth rate has declined substantially. Although much sophisticated analysis of other data from the survey will be required to determine the extent of the contribution of oral contraception to this decline, the findings presented here suggest that the contribution is substantial for young married couples. The major effect on the couple's eventual number of children may be less than the effect on the time pattern of childbearing; in any event, both lower eventual parity and delayed fertility contribute to a decline in the numbers of births from year to year. Whatever the intent may be, it is apparent that young American couples have adopted a new means for achieving their reproductive goals.

Adolescent↗

Reproductive and sexual behavior changes in male rats exposed perinatally to picrotoxin.

Previous studies in rats suggested that picrotoxin, a GABA(A) receptor antagonist, may cause long-term changes in male reproductive physiology and behavior in rats exposed during prenatal and postnatal periods. The present study has further examined this phenomenon. Wistar rat dams were dosed subcutaneously with 0.75 mg/kg picrotoxin in saline, or vehicle alone, during the perinatal period (day 19 of gestation, immediately after parturition, and once a day during the first 5 days of lactation). Birth weight and sexual maturation of pups were unchanged; however, plasma testosterone levels and sexual behavior was altered in male offspring. Although fertile, these males showed altered mating behavior in terms of a decrease in the mean number of mounts during a 30-min observation period with normal females. Some showed homosexual behavior when castrated and pretreated with exogenous estrogen. These findings suggest that perinatal exposure to picrotoxin alters sexual dimorphism in the developing rat brain, manifesting as altered reproductive performance and sexual behavior of males.

Animals↗

The pathogenesis of Tourette's syndrome. A possible role for hormonal and excitatory neurotransmitter influences in brain development.

Tourette's syndrome (TS) is associated with prominent gender differences in clinical expression, tics with a sexual content, and a stabilization or improvement of symptoms after puberty. It is herein hypothesized that some tics can be viewed as inappropriately expressed (normally inhibited) fragments of primitive motor and vocal programs involved in reproductive activity. The brain regions involved in TS (basal ganglia and limbic system) are proposed to be counterparts in humans of those functioning in primitive reproductive behavior whose development and organization are under sex hormone control. It is further hypothesized that sex hormone action is mediated by excitatory neurotransmitter mechanisms such that an excessive trophic effect occurs early in development and a neurotoxic environment emerges later on. The defective gene in TS is hypothesized to influence these developmental processes. This hypothesis has implications for the investigation of the pathogenesis of TS and for experimental therapeutics of the disorder.

Amino Acids↗

Afferent and efferent connections of the diencephalic prepacemaker nucleus in the weakly electric fish, Eigenmannia virescens: interactions between the electromotor system and the neuroendocrine axis.

The afferent and efferent connections of the gymnotiform central posterior nucleus of the dorsal thalamus and prepacemaker nucleus (CP/PPn) were examined by retrograde and anterograde transport of the small molecular weight tracer, Neurobiotin. The CP/PPn was identified by physiological assay and received a local iontophoretic injection of Neurobiotin. Retrogradely labeled somata were observed in the ventral telencephalon, hypothalamus, and the pretectal nucleus electrosensorius. Anterogradely labeled fibers were traced from the CP/PPn to the ventral telencephalon, the hypothalamus, the neuropil immediately adjacent to the most rostral subdivision of the nucleus electrosensorius, the optic tectum, and the pacemaker nucleus. Retrograde transport of tracer following injections into the ventral telencephalon, preoptic area, lateral hypothalamus, tectum, and pacemaker nucleus confirmed these efferent targets. A rostromedial subarea of the CP/PPn can be identified that projects to basal forebrain regions and to a lateral region of the CP/PPn that contains afferents to the pacemaker. Many of the targets, which are connected with the CP/PPn, have been linked to reproductive behavior or neuroendocrine control in other fishes. A comparative analysis reveals that the efferent pathways of the CP/PPn appear similar and may be homologous to efferent pathways of some components of the auditory thalamus among tetrapods.

Afferent Pathways↗

Subnuclear organization of the rat habenular complexes.

The habenular complexes represent phylogenetically constant structures in the diencephalon of all vertebrates. Available evidence suggests that this area is engaged in a variety of important biological functions, such as reproductive behaviors, central pain processing, nutrition, sleep-wake cycles, stress responses, and learning. Based on Nissl-stained sections, one medial nucleus and two lateral nuclei (divisions) have been widely accepted in the rat. Cytochemical, hodologic, and functional studies suggest a considerably more complex subnuclear structure. To improve our knowledge of the precise structural composition of the habenular complexes, we have systematically investigated their fine ultrastructure in the rat. Based on the detailed analysis of complete series of large, semithin sections supplemented with electron photomicrographs of selected fields, clear criteria for the delineation of five distinct subnuclei of the medial and ten subnuclei of the lateral habenular complexes were elaborated for the first time. All 15 subnuclei were reconstructed, and their dimensions were determined. A medial and lateral stria medullaris were described. Different roots of the fasciculus retroflexus were differentiated within the medial and lateral habenular complexes. The topographical relationships with respect to the adjacent habenular areas as well as to the neighboring thalamic nuclei were identified and demonstrated. The new understanding of the subnuclear organization of the habenular complexes certainly will facilitate further functional investigations. Whether the newly identified subnuclei finally will be recognized as functionally distinct awaits ongoing immunocytochemical, hodologic, and functional studies.

Animals↗

Structure and diversity in mammalian accessory olfactory bulb.

The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of development. Finally, new areas in vomeronasal system research such as the diversity of receptor molecules and the regional variation in receptor neuron type as well as in the output neurons of the AOB and their projection pathways are briefly discussed. In view of the pronounced diversity of size, morphologic differentiation, and phylogenetic development, the need to explore new functions for the vomeronasal system in areas other than sexual and reproductive behaviors is emphasized.

Animals↗

clk-1, mitochondria, and physiological rates.

Mutations in the C. elegans maternal-effect gene clk-1 are highly pleiotropic, affecting the duration of diverse developmental and behavioral processes. They result in an average slowing of embryonic and post-embryonic development, adult rhythmic behaviors, reproduction, and aging.(1) CLK-1 is a highly conserved mitochondrial protein,(2,3) but even severe clk-1 mutations affect mitochondrial respiration only slightly.(3) Here, we review the evidence supporting the regulatory role of clk-1 in physiological timing. We also discuss possible models for the action of CLK-1, in particular, one proposing that CLK-1 is involved in the coordination of mitochondrial and nuclear function. BioEssays 22:48-56, 2000.

Amino Acid Sequence↗

Monosynaptic projections from the nucleus retroambiguus to motoneurons supplying the abdominal wall, axial, hindlimb, and pelvic floor muscles in the female rhesus monkey.

The nucleus retroambiguus (NRA) consists of premotor neurons in the caudal medulla. It is involved in expiration, vomiting, vocalization, and probably reproductive behavior by means of projections to distinct motoneuronal cell groups. Because no information is available about the NRA and its efferent pathways in primates, the present study examines NRA projections to the lumbosacral spinal cord in female rhesus monkeys. To identify the NRA, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the lumbosacral cord in three monkeys. To study the distribution of NRA axons in the lumbosacral cord, WGA-HRP injections were made into the NRA in seven monkeys. To identify motoneuronal cell groups receiving input from the NRA, the same seven monkeys also received cholera toxin subunit b (CTb) injections into different hindlimb, axial, and pelvic floor muscles. The results show that NRA neurons projecting to the lumbosacral cord are mainly located between 1 to 4 mm caudal to the obex. They send numerous axons to external oblique and pelvic floor motoneurons, whereas projections to iliopsoas and axial motoneurons are less numerous. The projections are bilateral, but show a clear contralateral predominance in the iliopsoas, axial, and pelvic floor motoneuronal cell groups. At the ultrastructural level, NRA-terminal profiles make asymmetrical contacts with labeled and unlabeled dendrites in these motoneuronal cell groups and contain large amounts of spherical and a few dense core vesicles. It is concluded that the NRA is well developed in the monkey and that there exists a direct pathway from the NRA to lumbosacral motoneurons in this species. The finding that the NRA projects to a somewhat different set of motoneuronal cell groups compared with other species fits the concept that it is not only involved in expiration-related activities but also in species specific receptive and submissive behavior.

Abdominal Muscles↗

Comparative morphology and histochemistry of glands associated with the vomeronasal organ in humans, mouse lemurs, and voles.

The vomeronasal organ (VNO) is a chemosensory structure of the vertebrate nasal septum that has been recently shown to exist in nearly all adult humans. Although its link to reproductive behaviors has been shown in some primates, its functionality in humans is still debated. Some authors have suggested that the human VNO has the capacity to detect pheromones, while others described it as little more than a glandular pit. However, no studies have utilized histochemical techniques that would reveal whether the human VNO functions as a generalized gland duct or a specialized chemosensory organ. Nasal septal tissue from 13 humans (2-86 years old) were compared to that of two adult lemurs (Microcebus murinus) and eight adult voles (four Microtus pennsylvanicus and four Microtus ochrogaster). Sections at selected intervals of the VNO were stained with periodic acid-Schiff (PAS), alcian blue (AB), AB-PAS, and PAS-hematoxylin procedures. Results revealed typical well-developed VNOs with tubuloacinar glands in Microtus and Microcebus. VNO glands were AB-negative and PAS-positive in voles and mouse lemurs. Homo differed from Microtus and Microcebus in having more branched, AB and PAS-positive glands that emptied into the VNO lumen. Furthermore, the human VNO epithelium had unicellular mucous glands (AB and PAS-positive) and cilia, similar to respiratory epithelia. These results demonstrate unique characteristics of the human VNO which at once differs from glandular ducts (e.g., cilia) and also from the VNOs of mammals possessing demonstrably functional VNO.

Adolescent↗

The nasopalatine ducts and associated structures in the rhesus monkey (Macaca mulatta): topography, prenatal development, function, and phylogeny.

Morphological and developmental characteristics of the rhesus monkey nasopalatine duct system and associated primary palatal structures are described along with functional and phylogenetic considerations. Examination of five adult palates and coronal sections of 13 fetal palates together with dissections of a sixth adult specimen and of a 119-day-old fetal palate reveal that the lateral lobes of the tripartate incisive papilla cover clefts leading into the ducts. The ducts pierce the bony palate to enter the nasal fossae in proximity to the incisive suture. The ontogenetic stability of the duct path reflects the retention of ancient duct and primitive choanae relationships and functionally maintains an optimal oral odorant-to-receptor channel. Sixteen timed pregnancy specimens (35-100 days) provided histological material for documenting rostral nasopalatal development. Duct primordia, identified at 35 days, had by 40 days formed the medial duct walls (conjoined septum-papilla from the primary medial palatal component), the lateral duct walls (maxillary processes), and the rostral walls (fused maxillary-intermaxillary components). The caudal walls derive from the fusion of palatal shelves with the papilla (45 days), thus distinguishing primary and secondary fusion modes. Duct epithelial maturation occurs between 70 and 100 days. The absence of a vomeronasal system is attributed to reduction of olfaction in reproductive behavior, while the presence of the coevolved nasopalatine ducts is linked to the persistence of epiglottal-velar valving. The ducts serve as oral food-odor conduits in otherwise functionally separated respiratory and digestive tracts.

Animals↗