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Critical period for degradation of adult rat retinal ganglion cells and their regeneration capability after axotomy.

The optic nerve (ON) in adult rats was transected intraorbitally followed by retrograde labelling of retinal ganglion cells (RGCs) with fluorescence dye (DiI). A two phase reduction of axotomized RGCs was represented in the retina until 15 days after ON transection. The critical period of RGC loss is around 7 days after axotomy. In this period, the capability of neurite regeneration from RGCs in culture was strongly intensified by ON transection. These findings indicate that the 7th day after axotomy is important for both RGC survival and regeneration.

Animals↗

Tutorial in Biostatistics: Evaluating the impact of 'critical periods' in longitudinal studies of growth using piecewise mixed effects models.

Recent developments in modern multivariate methods provide applied researchers with the means to address many important research questions that arise in studies with repeated measures data collected on individuals over time. One such area of applied research is focused on studying change associated with some event or critical period in human development. This tutorial deals with the use of the general linear mixed model for regression analysis of correlated data with a two-piece linear function of time corresponding to the pre- and post-event trends. The model assumes a continuous outcome is linearly related to a set of explanatory variables, but allows for the trend after the event to be different from the trend before it. This task can be accomplished using a piecewise linear random effects model for longitudinal data where the response depends upon time of the event. A detailed example that examines the influence of menarche on changes in body fat accretion will be presented using data from a prospective study of 162 girls measured annually from approximately age 10 until 4 years post menarche.

Adipose Tissue↗

Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity.

Antibodies that block Sonic Hedgehog (SHH) signaling have been used to show that SHH activity is required for the induction of floor plate differentiation by the notochord and independently for the induction of motor neurons by both the notochord and midline neural cells. Motor neuron generation depends on two critical periods of SHH signaling: an early period during which naive neural plate cells are converted into ventralized progenitors and a late period that extends well into S phase of the final progenitor cell division, during which SHH drives the differentiation of ventralized progenitors into motor neurons. The ambient SHH concentration during the late period determines whether ventralized progenitors differentiate into motor neurons or interneurons, thus defining the pattern of neuronal cell types generated in the neural tube.

Animals↗

Is there a critical period for bone response to weight-bearing exercise in children and adolescents? a systematic review.

This systematic review examines and compares the bone mineral changes in children and adolescents, as measured by dual energy x ray absorptiometry, reported in exercise intervention studies. The effects of hormonal factors and growth on bone mineral change during puberty are examined, and the possibility of a critical period during which bone is especially adaptable to exercise is discussed.

Absorptiometry, Photon↗

Modification of neurotransmitter receptor sensitivity in cat visual cortex during the critical period.

We have examined the characteristics of various receptors in cat visual cortex during postnatal development. These included beta-adrenergic, GABA, benzodiazepine and acetylcholine receptors. For each population of receptor the number (Bmax) and affinity (Kd) were examined as a function of postnatal age (3 days-adult). For all receptors examined, the Bmax increased during development from low early values to a peak within the critical period. The Kd also changed during development for most receptors. The simultaneous alterations in Bmax and Kd necessitate defining a term which takes both of these receptor properties into consideration. This term, called receptor sensitivity (RS), provides a more comprehensive measure of receptor function than either Bmax or Kd alone. Using this measure, we find that receptor sensitivity is low near birth for the 4 receptor populations studied, rises to a peak within the first two months of life, and then declines to near-neonatal levels for 3 of the 4 receptor populations.

Animals↗

Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: role of a serotonin excess during the critical period.

In a transgenic mouse line (Tg8) deficient for the gene encoding monoamine oxidase A (MAOA), we show that the primary somatosensory cortex (S1) lacks the characteristic barrel-like clustering of layer IV neurons, whereas normal pattern formation exists in the thalamus and the trigeminal nuclei. No barrel-like patterns were visible with tenascin or serotonin immunostaining or with labeling of thalamocortical axons. An excess of brain serotonin during the critical period of barrel formation appears to have a causal role in these cortical abnormalities, since early administration of parachlorophenylalanine, an inhibitor of serotonin synthesis, in Tg8 pups restored the formation of barrels in S1, whereas inhibition of catecholamine synthesis did not. Transient inactivation of MAOA in normal newborns reproduced a barrelless phenotype in parts of S1.

Animals↗

Critical periods for foetal mortality in gilts identified by analysing the length distribution of mummified foetuses and frequency of non-fresh stillborn piglets.

The objective of this study was to investigate the timing of foetal mortality in gilts of a segregating F2 cross of Large White and Meishan pigs on the basis of the length distribution of mummified foetuses and the frequency of non-fresh stillborn piglets in order to establish whether critical periods for foetal mortality exist. All expelled conceptuses and placentae of 192 farrowing gilts with a normal health status were meticulously investigated to recover all mummified foetuses. The length of each mummified foetus was measured. The predicted number of foetuses present per gilt at the early foetal stage of gestation was calculated as the sum of numbers of mummified foetuses and non-fresh stillborn, fresh stillborn and liveborn piglets. Foetal loss was calculated as the sum of mummified foetuses and non-fresh stillborn piglets. The average foetal mortality rate per gilt was 8.7%. In total 162 mummified foetuses were found (average 0.84 per litter), ranging in length from 0.4 to 33.0 cm. This indicates a range in foetal age at death of approximately 35-100 days. Although mummified foetuses of all lengths within the above mentioned range were found, relatively many had a length of less than 4 cm or of 10-21 cm. The total number of non-fresh stillborn piglets (i.e. late foetal deaths) was 58 (average 0.30 per litter). It can be concluded that foetal mortality occurred in these gilts throughout the period from day 35 to term, with relatively high incidences at the early foetal stage (days 35-40), shortly after mid-pregnancy (days 55-75) and after approximately day 100 of gestation. These three periods coincide with reported periods of change in porcine placental growth.

Abortion, Veterinary↗

Prominent expression of protein kinase C (gamma) mRNA in the dendrite-rich neuropil of mice cerebellum at the critical period for synaptogenesis.

It has been suggested that the expression of type 1 (gamma) protein kinase C(PKC) plays an active role in synaptogenesis. In situ hybridization assisted by an original computer image analysis technique (superimposition method) enabled the identification of PKC mRNA expression in the dendrite-rich neuropil area of the cerebellum. This study revealed prominent expression of PKC mRNA in the dendrite-rich neuropil area of the cerebellum at the critical period for synaptogenesis compared with adult mice cerebellum. Therefore, it is suggested that PKC mRNA in the dendrites of Purkinje cells plays an important role in synaptogenesis.

Algorithms↗

[Stages in the postnatal maturation of the optic nerve: morphometric changes during the critical period].

The postnatal differentiation in rat optic nerve fibers was examined by electron microscopy from birth until the age of 44 days. We have estimated the evolution of the following parameters: nerve, axons and fibers caliber, number of axons, number and density of microtubules and neurofilaments, and number of myelin lamellae. In this study, we have determined four phases in the postnatal maturation of the optic nerve fibers, and we have described the ultrastructural changes during the critical period. The first week is a period of slow growth in axonal size and there is a lack of myelinated fibers. Microtubules and neurofilaments are relatively stable at this time, being the microtubules more numerous. The second phase corresponds with the second and third postnatal weeks, and shows a rapid increase in axonal size, microtubule and neurofilament number. The number of neurofilaments was more numerous than the number of microtubules. The third phase corresponds with the fifth postnatal week, and there are no changes in axonal caliber and in microtubule and neurofilament number. The fourth and last phase occurred from the sixth postnatal week to adult age. In this phase the axonal size, the fiber caliber, the microtubule and the neurofilament number increased. Our findings support the idea that neurofilaments are the most relevant morphological structure in the determination of axonal maturation in rat optic nerve.

Animals↗

Hemolymph ecdysteroid titer and ecdysteroid-dependent developmental events in the last-larval stadium of the silkworm, Bombyx mori: role of low ecdysteroid titer in larval-pupal metamorphosis and a reappraisal of the head critical period.

The endocrine regulation of larval-pupal metamorphosis was studied in the silkworm, Bombyx mori, by measuring the following changes: hemolymph ecdysteroid titer, the secretory activity of prothoracic glands and the responsiveness of larvae to ecdysteroids and prothoracicotropic hormone (PTTH), with regard to developmental events such as the occurrence of spinneret pigmentation, initiation of cocoon spinning and onset of wandering stage as indicated by gut purge. These measurements were concentrated especially on the time before and after the head critical period (HCP) which falls 3-4 days before the gut purge ([Sakurai, 1984]). A small increase in the hemolymph ecdysteroid titer was first found during the HCP, and then the titer increased with daily fluctuations. Small but significant titer peaks were found prior to the occurrence of both spinneret pigmentation and gut purge, indicating that an individual titer peak could possess a specific role in development. Responsiveness of larvae to exogenous 20-hydroxyecdysone (20E) after the HCP was markedly higher than that before the HCP. The sensitivity of the prothoracic gland to PTTH also changed during the HCP. The results thus showed that the HCP is not the period after which an additional PTTH release is not required for the developmental events occurring on schedule, but rather it is the period during which complex events occur not only in the endocrine glands but also in the peripheral tissues. In addition, various developmental phenomena before gut purge are brought about by the hemolymph ecdysteroid whose concentration gradually increased with daily fluctuations, and these precise changes in the titer appeared to be important for the sequential occurrence of developmental events in the larval-pupal metamorphosis.

Journal Article↗

Critical periods in rat motoneuron development.

Reinnervation of rat internal intercostal muscles was examined 2 weeks after intramuscular axotomy in the period embryonic Day 17 (E17) to postnatal Day 2 (PN2). The efficiency of reinnervation depended on the day of denervation. Responses to nerve stimulation were common only in muscles denervated in the interval E19-21. Functional reinnervation was seldom seen in muscles denervated earlier, and was absent in muscles denervated shortly after birth. We suggest that there are "critical periods" in the sequence of differentiation of motoneurons. At E17 these neurons are very susceptible to cell death and any that lose contact with their muscle will die. Motoneurons axotomized later, while motor unit size is still increasing, can regenerate some functional nerve-muscle junctions. Motor unit size reaches its maximum by E21 and if motoneurons are axotomized after that time, in neonates, they cannot form more synaptic terminals although they can still extend axons. During this early postnatal period motoneurons normally reduce their number of nerve-muscle contacts. Finally, at 3 weeks of age, motoneurons reach their adult state when they are capable of regeneration relatively unhindered by restrictions on the number and location of their peripheral connections.

Animals↗

Critical periods of early development created by the coordinate modulation of ion channel properties.

The development of ion channel properties in excitable cells begins in the very early embryo and continues throughout differentiation. The pattern of ion channel development in a given cell type is not a simple linear progression to the mature state, but rather is a complex sequence of modulatory events that create windows of time during which excitability is qualitatively different from that in the mature cell. These windows are likely candidates for critical periods when electrical activity influences later development.

Animals↗

Natural selection of the critical period for language acquisition.

The language acquisition period in humans lasts about 13 years. After puberty it becomes increasingly difficult to learn a language. We explain this phenomenon by using an evolutionary framework. We present a dynamical system describing competition between language acquisition devices, which differ in the length of the learning period. There are two selective forces that play a role in determining the critical learning period: (i) having a longer learning period increases the accuracy of language acquisition; (ii) learning is associated with certain costs that affect fitness. As a result, there exists a limited learning period which is evolutionarily stable. This result is obtained analytically by means of a Nash equilibrium analysis of language acquisition devices. Interestingly, the evolutionarily stable learning period does not maximize the average fitness of the population.

Biological Evolution↗

Effect of embryonic treatment with estradiol or testosterone on sexual differentiation of the quail brain. Critical period and dose-response relationships.

Japanese quail eggs were injected with estradiol benzoate (EB) after 10, 11, 12, 13, or 14 days of incubation, or were injected on day 10 with one of six dosages of EB or seven dosages of testosterone propionate (TP). EB injected on day 10 of 11 demasculinized the males; as adults they were incapable of copulating in response to exogenous TP. EB injected on day 13 or 14 was without effect, and EB injected on day 12 caused slight demasculinization. The critical period for sexual differentiation of the brain appears to end after about 12 days of incubation in this species. As little as 1 microgram EB reduced masculine sexual behavior. Injection of TP at dosages equal to or greater than 100 micrograms also demasculinized male quail.

Animals↗

Critical periods in the prenatal morphogenesis of the human lateral pterygoid muscle, the mandibular condyle, the articular disk, and medial articular capsule.

This study was prompted by the renewed clinical interests in understanding the natural history or early morphogenesis of the human temporomandibular joint. Using histologic preparations of 52 representative human embryos and fetuses, each of the major components of the joint was systematically assessed for its changing structure and related to an approximate time scale. The emergence and continued morphogenesis of the joint articular fossa, mandibular condyle, disk, capsule, lateral pterygoid muscle fibers, and both joint cavities occur in regular temporal and spatial pattern. A key observation from this study of embryos and fetuses ranging in age from 32 days to 22 weeks is that each of the component parts of the TMJ progressively emerge with some kind of continuity from a common mass of embryonic mesenchyme interposed between the future temporal bone and mandibular regions. The observations of this study lead to the suggestion that significant developmental disturbances to this common tissue mass or "developmental field" can lead to anomalous morphogenesis of those structures expected to emerge over time from the "developmental field" of the temporomandibular joint. Timing and the identification of a critical time period for the joint are important variables. This study identifies the critical period in the early morphogenesis of TMJ structures as generally falling between the early 7th and 11th prenatal weeks.

Cartilage, Articular↗

A critical period requiring Rho proteins for cell cycle progression uncovered by reversible protein transduction in endothelial cells.

The time-specific requirement of Rho proteins for the S phase progression of vascular endothelial cells was determined by reversibly introducing inhibitor proteins with a cell-penetrating peptide. We found evidence of the reversibility of protein transduction. The removal of extracellular protein caused the transduced protein to decay in a manner sensitive to low temperatures. The time required for a 50% decay correlated with the protein size. The time-specific transduction of the inhibitor proteins uncovered a critical period requiring Rho proteins in the G1-S transition phase. Reversible protein transduction may thus be a powerful tool to investigate the time-specific role of signaling proteins.

Animals↗

Kinetics of induction of transplantation tolerance with a nondepleting anti-Cd4 monoclonal antibody and donor-specific transfusion before transplantation. A critical period of time is required for development of immunological unresponsiveness.

The combination of a depleting anti-Cd43 monoclonal antibody (mAb) and a single donor-specific transfusion before transplantation has been shown to induce operational transplantation tolerance in the majority of cardiac allograft recipients in a mouse model. To examine a protocol which might be more clinically relevant, we have modified this tolerance-inducing protocol by substituting the depleting with a nondepleting anti-Cd4 mAb. We show that this form of pretreatment can also induce immunologic unresponsiveness in most recipients (C3H/He, H2(k)), provided a critical period of time, in this case 28 days, is allowed between pretreatment and transplantation of a fully mismatched heart graft (H2(b)). When only 1 or 2 weeks were allowed between pretreatment and transplantation, only slight graft prolongation was obtained when compared with recipients receiving anti-Cd4 mAb alone, at these time points. Maintenance of tolerance in this model was due, at least in part, to active mechanisms as immunologic unresponsiveness to donor antigens could be transferred to naive syngeneic mice by splenocytes from recipients bearing long-term functioning grafts. These findings suggest that a population of regulatory cells develop after pretreatment with nondepleting anti-Cd4 mAb and donor-specific transfusion, and that it takes at least 1 month for these cells to expand and effectively drive the recipient's immune system toward immunologic unresponsiveness.

Animals↗

A critical period for retinoic acid teratogenesis and loss of neurophilic migration of pontine nuclei neurons.

Abnormalities in the pontine nuclei (PN) and inferior olive are hallmarks of human retinoic acid (RA) teratogenesis. This study shows that RA exposure of the mouse at a specific embryonic stage alters morphological structures that derive from the wall of the IVth ventricle to form components of the precerebellar system (the inferior olivary nucleus and the PN). The study employs both normal and a RAREhspLacZ transgenic RA reporter mouse. It is shown that abnormalities in the PN and inferior olive result from exposure at a critical period of embryonic day 9.5 and 10.5. The abnormalities in the PN are due to a failure in their usual neurophilic migration. The compact stream of cells that leads from the anterior rhombic lip to the ventral pons is instead scattered widely over the anterior medulla. Given that the RA exposure occurs after the resolution of rhombomere identity this suggests that teratogenic RA interferes with a regulatory event that overlays this original pattern.

Abnormalities, Drug-Induced↗