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Developmental regulation of leucine-enkephalin expression in adrenal chromaffin cells by glucocorticoids and innervation.

Most catecholaminergic cells derived from the sympathoadrenal lineage of the neural crest contain one or more neuropeptides. Although a great deal is known about the development and regulation of catecholaminergic properties in these cells, relatively little is known about the developmental control of their neuropeptidergic properties. We have investigated the possible role of glucocorticoids and preganglionic innervation in the regulation of leucine-enkephalin (L-Enk) expression in cultures of embryonic and neonatal adrenal chromaffin cells and in mature chromaffin cells in vivo. Exposure of embryonic and neonatal chromaffin cells to the synthetic glucocorticoid dexamethasone increases L-Enk content. Neonatal chromaffin cells grown in medium containing elevated levels of potassium to mimic depolarization also exhibited increased L-Enk levels. The depolarization-induced increase in L-Enk was selectively inhibited by treatment with the enkephalin analog [D-Ala, d-Leu]-enkephalin to mimic the enkephalinergic component of the preganglionic innervation. Denervation of the adrenal gland in vivo resulted in a dramatic increase in L-enk expression that could be partially mimicked by selectively blocking enkephalinergic transmission with administration of the opiate receptor antagonist naloxone. Taken together with the developmental time course and pattern of L-Enk expression in vivo, our results suggest that glucocorticoids and the preganglionic innervation regulate the developmental expression of this peptide in adrenal chromaffin cells and therefore participate in the generation of the mature neurochemical phenotypes present in the adrenal medulla. Further, in adult chromaffin cells similar factors appear to regulate the expression of L-Enk, which could in turn participate in physiological responses to stress.

Adrenal Glands↗

Toxicity of insecticides to Toxorhynchites splendens and three vector mosquitos and their sublethal effect on biocontrol potential of the predator.

Toxicity of six larvicides ie fenthion, temephos, malathion, deltamethrin, alphamethrin (Fendona), OMS 3031 and five adulticides ie malathion, fenitrothion, propoxur, deltamethrin, permethrin to Aedes aegypti, Culex quiquefasciatus, Anopheles stephensi and the predator, Toxorhynchites splendens was studied for evaluating safety margin. Concentrations of alphamethrin that killed 50% larvae of T. splendens were 53 and 12 times more than that which killed Cx. quinquefasciatus and Ae. aegypti. In case of deltamethrin, concentrations required to kill 50% larvae of T. splendens were 14 and 5 times more than that required against other two species. Other larvicides tested were equally toxic to both T. splendens and vector mosquitos. There was no significant difference in the toxicity of larvicides to T. splendens and An. stephensi. Deltamethrin was 25-132 times less toxic to adults of T. splendens in comparison to vector mosquitos. For other adulticides the range was 1-10. Immature developmental time of T. splendens was not affected by any of the insecticides tested. However, predation rate was lowered when larvae of Ae. aegypti previously exposed to fenthion and temephos were offered. Whereas, alphamethrin and OMS 3031 did not affect the feeding rate of the predator. There was a significant reduction in the pupal weight and pupation as a result of the predator feeding on the insecticide treated prey. There was a significant negative relationship between rate of pupation and dosage. The present study indicates that synthetic pyrethroids owing to their higher safety margin can be used in an integrated vector management program.

Aedes↗

Evidence for a phase transition in the early development of prehension.

A longitudinal study was conducted to examine the hypothesis that the development of prehension during the first 5 months of life is characterized by the presence of a discontinuous phase transition. Ten infants were observed weekly from 8 to 24 weeks of age. Video recordings were made of movements toward an attractive object which were classified according to two behavioral categories: reaching without grasping and reaching with grasping. The time evolution of the relative incidence of these behavioral categories was analyzed statistically. Evidence was found for a sudden jump from a (developmental) state in which reaching without grasping is predominant to a state in which reaching with grasping is predominant. Evidence was also found for bimodality, inaccessibility, and anomalous variance. In combination, these findings support the hypothesis that the investigated behavioral change constitutes a discontinuous phase transition. The behavioral change in question occurred at the moment in developmental time at which the attractor strength of reaching for objects as such relative to that of other behavioral activities appeared to be increased.

Age Factors↗

Insect seasonality: circle map analysis of temperature-driven life cycles.

Maintaining an adaptive seasonality, with life cycle events occurring at appropriate times of year and in synchrony with cohorts and ephemeral resources, is a basic ecological requisite for many cold-blooded organisms. There are many mechanisms for synchronizing developmental milestones, such as egg laying (oviposition), egg hatching, cocoon opening, and the emergence of adults. These are often irreversible, specific to particular life stages, and include diapause, an altered physiological state which can be reversed by some synchronizing environmental cue (e.g. photoperiod). However, many successful organisms display none of these mechanisms for maintaining adaptive seasonality. In this paper, we briefly review the mathematical relationship between environmental temperatures and developmental timing and discuss the consequences of viewing these models as circle maps from the cycle of yearly oviposition dates and temperatures to oviposition dates for subsequent generations. Of particular interest biologically are life cycles which are timed to complete in exactly 1 year, or univoltine cycles. Univoltinism, associated with reproductive success for many temperate species, is related to stable fixed points of the developmental circle map. Univoltine fixed points are stable and robust in broad temperature bands, but lose stability suddenly to maladaptive cycles at the edges of these bands. Adaptive seasonality may therefore break down with little warning with constantly increasing or decreasing temperature change, as in scenarios for global warming. These ideas are illustrated and explored in the context of Mountain Pine Beetle (Dendroctonus ponderosae Hopkins) occurring in the marginal thermal habitat of central Idaho's Rocky Mountains. Applications of these techniques have not been widely explored by the applied math community, but are likely to provide great insight into the response of biological systems to climate change.

Animals↗

Inverting the hourglass: quantitative evidence against the phylotypic stage in vertebrate development.

The concept of a phylotypic stage, when all vertebrate embryos show low phenotypic diversity, is an important cornerstone underlying modern developmental biology. Many theories involving patterns of development, developmental modules, mechanisms of development including developmental integration, and the action of natural selection on embryological stages have been proposed with reference to the phylotypic stage. However, the phylotypic stage has never been precisely defined, or conclusively supported or disproved by comparative quantitative data. We tested the predictions of the 'developmental hourglass' definition of the phylotypic stage quantitatively by looking at the pattern of developmental-timing variation across vertebrates as a whole and within mammals. For both datasets, the results using two different metrics were counter to the predictions of the definition: phenotypic variation between species was highest in the middle of the developmental sequence. This surprising degree of developmental character independence argues against the existence of a phylotypic stage in vertebrates. Instead, we hypothesize that numerous tightly delimited developmental modules exist during the mid-embryonic period. Further, the high level of timing changes (heterochrony) between these modules may be an important evolutionary mechanism giving rise to the diversity of vertebrates. The onus is now clearly on proponents of the phylotypic stage to present both a clear definition of it and quantitative data supporting its existence.

Animals↗

A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA.

The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals. We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA. Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression.

Animals↗

Regulation of flowering time and floral organ identity by a MicroRNA and its APETALA2-like target genes.

MicroRNAs (miRNAs) are approximately 21-nucleotide noncoding RNAs that have been identified in both animals and plants. Although in animals there is direct evidence implicating particular miRNAs in the control of developmental timing, to date it is not known whether plant miRNAs also play a role in regulating temporal transitions. Through an activation-tagging approach, we demonstrate that miRNA 172 (miR172) causes early flowering and disrupts the specification of floral organ identity when overexpressed in Arabidopsis. miR172 normally is expressed in a temporal manner, consistent with its proposed role in flowering time control. The regulatory target of miR172 is a subfamily of APETALA2 (AP2) transcription factor genes. We present evidence that miR172 downregulates these target genes by a translational mechanism rather than by RNA cleavage. Gain-of-function and loss-of-function analyses indicate that two of the AP2-like target genes normally act as floral repressors, supporting the notion that miR172 regulates flowering time by downregulating AP2-like target genes.

Arabidopsis↗

Modulation of gene expression by genetic and environmental heterogeneity in timing of a developmental milestone.

The expression of many important behavioral outcomes is contingent on passing a developmental milestone, such as puberty, or exposure to an age-dependent risk factor, such as alcohol or drugs. Current models for genetic effects on development have not provided explicit theoretical insight about possible patterns of epistasis and genotype x environment interaction generated by genetic and environmental heterogeneity in the timing of developmental milestones that influence gene expression. We explore theoretically the effects of individual differences in the timing of a developmental milestone on the expression of genetic differences in outcome. The consequences of additive genetic variation and shared environmental variation on timing are examined. Additive genetic effects on timing generate transient epistatic effects on outcome because they modulate the expression of otherwise additive genetic differences in outcome. Epistatic effects will be greatest at ages when there is the most heterogeneity in developmental maturity. Epistasis will gradually disappear as proportionately more individuals mature. Similarly, shared environmental effects on the timing of a milestone will generate transient genotype x shared environment interaction appearing as shared environmental effects on outcome that are greatest when there is the most heterogeneity in developmental maturity. The impact of these effects on age patterns in twin correlations is examined and their relevance to current data on developmental change discussed briefly.

Adolescent↗

Three cell recognition changes accompany the ingression of sea urchin primary mesenchyme cells.

At gastrulation the primary mesenchyme cells of sea urchin embryos lose contact with the extracellular hyaline layer and with neighboring blastomeres as they pass through the basal lamina and enter the blastocoel. This delamination process was examined using a cell-binding assay to follow changes in affinities between mesenchyme cells and their three substrates: hyalin, early gastrula cells, and basal lamina. Sixteen-cell-stage micromeres (the precursors of primary mesenchyme cells), and mesenchyme cells obtained from mesenchyme-blastula-stage embryos were used in conjunction with micromeres raised in culture to intermediate ages. The micromeres exhibited an affinity for hyalin, but the affinity was lost at the time of mesenchyme ingression in vivo. Similarly, micromeres had an affinity for monolayers of gastrula cells but the older mesenchyme cells lost much of their cell-to-cell affinity. Presumptive ectoderm and endoderm cells tested against the gastrula monolayers showed no decrease in binding over the same time interval. When micromeres and primary mesenchyme cells were tested against basal lamina preparations, there was an increase in affinity that was associated with developmental time. Presumptive ectoderm and endoderm cells showed no change in affinity over the same interval. Binding measurements using isolated basal laminar components identified fibronectin as one molecule for which the wandering primary mesenchyme cells acquired a specific affinity. The data indicate that as the presumptive mesenchyme cells leave the vegetal plate of the embryo they lose affinities for hyalin and for neighboring cells, and gain an affinity for fibronectin associated with the basal lamina and extracellular matrix that lines the blastocoel.

Animals↗

Effects of larval density on the size of Aedes polynesiensis adults (Diptera: Culicidae).

Replicated cohorts of a Tahitian laboratory strain of Aedes polynesiensis Marks were reared at 3 larval densities with a fixed amount of food. For larvae provided with limiting per capita food (i.e., 400 larvae per pan with 500 mg liver powder) relative to standard rearing conditions (i.e., 200 larvae per pan), mean pupal survival as well as male and female mean adult dry weights were significantly reduced and median developmental times were significantly prolonged. However, excess per capita food did not allow low density cohorts (i.e., 100 larvae per pan) to increase adult production, developmental rate, or adult dry weight compared with cohorts reared under standard rearing conditions. Male and female pupal wet weights, adult dry weights, and adult wing lengths all were correlated for Ae. polynesiensis collected as pupae from natural habitats near Papara Commune, Tahiti. Mean adult dry weights of host-seeking females from the same and a neighboring location did not differ significantly from weights of females emerging from field-collected pupae. The comparison of mean adult dry weight of these adults with adults reared at different densities in the laboratory indicated that field populations develop under food-limited conditions. Aedes polynesiensis responds to intraspecific larval competition by producing small adults over elongated developmental periods. Pupal wet weights, adult dry weights, and adult wing lengths are equally acceptable measures of mosquito size for vector and fecundity studies.

Aedes↗

Prenatal cocaine produces biochemical and functional changes in brain serotonin systems in rat progeny.

These studies demonstrate that prenatal cocaine produces differential changes in neuroendocrine responses following challenge with a 5-HT releaser versus a 5-HT1A agonist and suggest differential functional alterations in both pre- and postsynaptic components of 5-HT pathways. The attenuated neuroendocrine responses in adult male progeny following challenge with a 5-HT releaser, in the absence of reductions in 5-HT receptors, provide additional evidence in support of a presynaptic 5-HT deficit in adult male cocaine-exposed progeny. Furthermore, since prenatal cocaine produced a differential profile of alterations in 5-HT-mediated neuroendocrine responses in adult male (i.e., decreases ACTH and renin) versus prepubescent female (i.e., decreases ACTH and corticosterone) progeny following challenge with a 5-HT releaser, these data indicate that the differences could be due to gender and/or postnatal developmental ages. Gender differences in prenatal cocaine effects on postsynaptic receptor function were more clearly shown in study II, which demonstrated that at the same postnatal age, 5-HT1A-mediated neuroendocrine responses were significantly potentiated in male but not female cocaine-exposed progeny. In summary, the data presented in this chapter indicate that the biochemical and functional changes in 5-HT systems observed following prenatal exposure to cocaine are unique with respect to pre- versus postsynaptic alterations, pre- versus postpubescent developmental times, and differences between genders. A number of general conclusions can be drawn from the data presented. The presence of marked neurochemical deficits at both pre- and postpubescent timepoints, in the absence of any visually apparent physical terata, emphasizes the importance of investigating the neurochemical teratogenic potential of cocaine and other psychostimulants. Furthermore, data from these studies demonstrate the importance of investigating male and female progeny separately, as prenatal cocaine exposure may produce gender-specific alterations in some, but not all, aspects of brain neurotransmitter systems. Another important point that can be discerned from the present data is the necessity of subjecting cocaine-treated animals to challenge tests in order to reveal alterations that might not be readily apparent from measuring basal values for specific biochemical or functional parameters (e.g., basal hormone levels). In addition, the differential biochemical and functional changes in 5-HT systems, manifested at pre- versus postpubescent times, suggests that prenatal cocaine may adversely affect the normal maturational changes occurring in 5-HT systems. This may be of consequence in evaluating developmental stages in human offspring exposed to cocaine in utero. Furthermore, the ability of prenatal cocaine to alter 5-HT-mediated ACTH and renin responses in progeny suggest that offspring may exhibit alterations in their response to physiologic stimuli such as stress. Since neuroendocrine challenge tests can be performed in humans, the present data indicate the potential clinical utility of this approach to provide peripheral markers that can be used to identify changes in brain 5-HT pathways in human offspring exposed in utero to cocaine. Prenatal cocaine-induced alterations in brain 5-HT systems may be of significant clinical importance as dysfunction of 5-HT systems has been implicated in various psychiatric disorders including depression, anxiety, aggression, and drug-seeking behavior.

Animals↗

Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs.

We hypothesized that exposure of murine fetuses to environmental toxins, such as nitrofen, during early embryogenesis alters vasculogenesis. To address our hypothesis, we assessed protein levels of endothelial cell-selective angiogenic factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a transmembrane receptor tyrosine kinase. VEGF and Flk-1 proteins were lower in hypoplastic lungs from pseudoglandular to alveolar stages than in normal lungs at equivalent developmental time points significant for induction of pulmonary vasculogenesis and angiogenesis. ANG-1 protein was higher in hypoplastic lungs than in normal lungs at all the developmental stages considered in this study, i.e., pseudoglandular, canalicular, saccular, and alveolar stages. We assessed exogenous VEGF-mediated endothelial cell response on extracellular signal-regulated kinase (ERK) 1/2, also referred to as p44/42 mitogen-activated protein kinase. Hypoplastic lungs had more elevated ERK 1/2 protein than normal developing lungs. Exposure to exogenous VEGF activated ERK 1/2 in normal developing lungs but not in hypoplastic lungs. Our results suggest that in hypoplastic lungs: 1) low VEGF signifies negative effects on vasculogenesis/angiogenesis and indicates altered endothelial-mesenchymal interactions; 2) increased ANG-1 protein may be required to maintain vessel integrity and quiescence; and 3) regulation of ERK 1/2 protein is affected in hypoplastic lungs. We speculate that extensive remodeling of blood vessels in hypoplastic lungs may occur to compensate for structurally and functionally defective vasculature.

Angiopoietin-1↗

Event-related potential studies in infants and children.

The current status of event-related potentials (ERPs) in infants and children is discussed based on a review of the relevant literature. Although the N100-P200 component evoked by tone stimuli is clearly detected using an odd-ball paradigm in children over approximately 6 years of age, that component evoked by speech stimuli is not clearly detected until at least 10 years of age. In contrast to the adult N100-P200 component evoked by speech stimuli, infants and young children show a positivity at a latency of about 85-120 ms and a negativity at about 200-240 ms. The definition of P300 in children has not yet been established. P300 latency evoked by both auditory and visual stimuli decreases throughout childhood and reaches the mature value by puberty or young adulthood. However, P300s elicited by auditory and visual stimuli show different developmental time courses from each other, suggesting that they may originate from different neural generators. The Nc component is elicited by a variety of attention-getting events in infants and children. Interestingly, the developmental change in the Nc amplitude parallels the maturational course of synaptogenesis in the frontal cortex, and the Nc latency reaches the mature value at the time when myelinogenesis is complete in the nonspecific thalamic radiation.

Arousal↗

Effects of equilibration time, precooling and developmental stage on the survival of mouse embryos cryopreserved by vitrification.

Factorial experiments were carried out to examine the effects of equilibration time, precooling and developmental stage on the postthaw in vitro survival of vitrified mouse embryos. Eight-cell embryos, compacted morulae, or blastocysts were cryopreserved using vitrification Solution 1 (VS1; 10% glycerol + 20% propylene glycol), and vitrification Solution 2 (VS2; 25% glycerol + 25% propylene glycol) in phosphate buffered saline + 10% calf serum. Each embryo stage group was first equilibrated in VS1 for 5, 10 or 20 min and then exposed to either a precooled ( approximately 4 degrees C) or nonprecooled ( approximately 20 degrees C) VS2 in a 0.25-ml straw before they were plunged directly into liquid nitrogen. Results of this study showed an interaction between precooling, equilibration time and developmental stage which affect significantly post-thaw embryo survival (P< 0.05). High survival rates were obtained after 10 min equilibration in VS1 irrespective of the embryo developmental stage. Precooling of the VS2 significantly improved the survival mainly of blastocysts. However, eight-cell and morula-stage embryos also showed high survival rates when they were exposed to precooled VS2 after 5 min equilibration in VS1. It was further observed that morulae usually exhibit high survival rates, and vitrification conditions are more critical for early and advanced stage embryo development.

Journal Article↗

Epigenetic reprogramming in mammalian development.

DNA methylation is a major epigenetic modification of the genome that regulates crucial aspects of its function. Genomic methylation patterns in somatic differentiated cells are generally stable and heritable. However, in mammals there are at least two developmental periods-in germ cells and in preimplantation embryos-in which methylation patterns are reprogrammed genome wide, generating cells with a broad developmental potential. Epigenetic reprogramming in germ cells is critical for imprinting; reprogramming in early embryos also affects imprinting. Reprogramming is likely to have a crucial role in establishing nuclear totipotency in normal development and in cloned animals, and in the erasure of acquired epigenetic information. A role of reprogramming in stem cell differentiation is also envisaged. DNA methylation is one of the best-studied epigenetic modifications of DNA in all unicellular and multicellular organisms. In mammals and other vertebrates, methylation occurs predominantly at the symmetrical dinucleotide CpG (1-4). Symmetrical methylation and the discovery of a DNA methyltransferase that prefers a hemimethylated substrate, Dnmt1 (4), suggested a mechanism by which specific patterns of methylation in the genome could be maintained. Patterns imposed on the genome at defined developmental time points in precursor cells could be maintained by Dnmt1, and would lead to predetermined programs of gene expression during development in descendants of the precursor cells (5, 6). This provided a means to explain how patterns of differentiation could be maintained by populations of cells. In addition, specific demethylation events in differentiated tissues could then lead to further changes in gene expression as needed. Neat and convincing as this model is, it is still largely unsubstantiated. While effects of methylation on expression of specific genes, particularly imprinted ones (7) and some retrotransposons (8), have been demonstrated in vivo, it is still unclear whether or not methylation is involved in the control of gene expression during normal development (9-13). Although enzymes have been identified that can methylate DNA de novo (Dnmt3a and Dnmt3b) (14), it is unknown how specific patterns of methylation are established in the genome. Mechanisms for active demethylation have been suggested, but no enzymes have been identified that carry out this function in vivo (15-17). Genomewide alterations in methylation-brought about, for example, by knockouts of the methylase genes-result in embryo lethality or developmental defects, but the basis for abnormal development still remains to be discovered (7, 14). What is clear, however, is that in mammals there are developmental periods of genomewide reprogramming of methylation patterns in vivo. Typically, a substantial part of the genome is demethylated, and after some time remethylated, in a cell- or tissue-specific pattern. The developmental dynamics of these reprogramming events, as well as some of the enzymatic mechanisms involved and the biological purposes, are beginning to be understood. Here we look at what is known about reprogramming in mammals and discuss how it might relate to developmental potency and imprinting.

Animals↗

Enhancer detector analysis of the extent of genomic involvement in nervous system development in Drosophila melanogaster.

We conducted a survey of the patterns of gene expression in the central nervous system (CNS) of larvae of the fruitfly Drosophila melanogaster to identify genes that may be important in the development of the CNS, aid in the recognition of basic organizing features that might underlie CNS development, and estimate the extent of the use of information encoded in the genome in the construction of the nervous system. A so-called enhancer detector strategy was used to generate many thousands of lines containing a beta-galactosidase reporter gene. These lines were screened as third-instar larvae for patterns of expression in the developing optic lobes and other portions of the CNS. Most of the lines recovered which evidence staining within the CNS could be included in one of a relatively small number of patterns. A random sample of 594 lines from the larger population screened was selected to quantify the relative frequencies of these patterns, and a more careful analysis of the changes in the patterns of expression with developmental time was done for representative lines of nine of the patterns. These studies demonstrated great variability in the pattern of gene expression as a function of developmental stage. Few, if any, lines showed beta-galactosidase activity limited to the optic lobes; similarly, few lines were identified in which staining was limited to only a small number of cells. Together with the limited number of patterns of gene expression seen, this suggests that in the larval CNS developmental pathways may be controlled by a combinatorial process of gene activity that involves the majority of the genome rather than by having a specific gene specify the fate of only a few neuronal precursors.

Animals↗

Timing of pubertal maturation and the onset of sexual behavior among Zimbabwe school boys.

The relationship between reproductive maturation and the onset of sexual behavior in boys across cultures is unclear. To explore the relative timing of pubertal events and their relationship to the onset of sexual behavior, we used data collected from 442 Zimbabwe school boys aged 12-18 years. Measures of reproductive maturation included self-reported spontaneous nocturnal emission, secondary sexual characteristics, and salivary testosterone. Behavioral measures included age at first sexual fantasies, non-coital sexual behavior, and coitus. Sigmoid interpolation curve techniques indicated a median age of first erection at 10.75 +/- 0.11 years, first sexual fantasy at 12.66 +/- 0.03 years, first spontaneous nocturnal emission at 13.02 +/- 0.03 years, and adult levels of blood testosterone at 17.2 +/- 0.7 years. First reported spontaneous nocturnal emission was significantly related to all measures of sexual behavior. Multiple regression models indicated that first reported spontaneous nocturnal emission was a stronger predictor of sexual behavior than variation in secondary sexual characteristics. In addition, testosterone was a significant predictor of sexual fantasies and intercourse, independent of first reported spontaneous nocturnal emission. These results confirm earlier findings in other populations that self-reported spontaneous nocturnal emissions can be used as a marker of pubertal timing among adolescent boys. They also suggest that variation in testosterone plays a role in the onset of sexual behavior among boys, beyond its relationship to developmental timing. The behavioral mechanisms represented by the significant effects of testosterone reported here remain to be investigated.

Adolescent↗

The ontogeny of the uptake systems for glutamate, GABA, and glycine in synaptic vesicles isolated from rat brain.

The ontogeny of the uptake of glutamate, GABA and glycine into synaptic vesicles isolated from rat brain has been investigated. The vesicular uptake of the three amino acids increased with developmental age in parallel with synaptogenesis, indicating a functional role of uptake of the amino acids by synaptic vesicles in the nerve terminals. Uptake of the amino acids by plasma membrane particles (synaptosomes) in brain homogenate showed a somewhat different developmental profile. The uptake of glutamate increased markedly with developmental time, while the uptake of GABA showed only a slight increase. Uptake of glycine by plasma membrane particles was very low and therefore not registered. The observed developmental increase in uptake of glycine by synaptic vesicles isolated from brain, supports previous reports indicating that glycine can be taken up by vesicles from non-glycine terminals.

Adenosine Triphosphate↗