Effects Of Early Development Research Articles

Postnatal treatment with ACTH-(4-9) analog ORG 2766 attenuates N-methyl- d-aspartate-induced excitotoxicity in rat nucleus basalis in adulthood

It has been reported that the ACTH-(4-9) analog H-Met(O 2)-Glu-His-Phe- d-Lys-Phe-OH (ORG 2766) administered in adulthood has trophic effects on neuronal tissue and when given postnatally, it can induce long-lasting changes in brain development. In the present study, we investigated whether early postnatal treatment with ORG 2766 affects adult neuronal vulnerability, i.e. the sensitivity of cholinergic neurons against excitotoxic damage. Wistar rat pups received injections of ORG 2766 or saline on postnatal days 1, 3 and 5 and were then left undisturbed until adulthood. At the age of 6 months, the animals were subjected to unilateral lesion of magnocellular basal nucleus by infusion of high dose of N-methyl- d-aspartate (NMDA). The effects of the excitotoxic insult were studied 28 hours and 12 days after the lesion by measuring both the acute cholinergic and glial responses, and the final outcome of the degeneration process. Twenty eight hours after NMDA infusion, postnatally ACTH-(4-9)-treated animals showed stronger suppression of choline-acetyltransferase immunoreactivity and increased reaction of glial fibrillary acidic protein -immunopositive astrocytes in the lesioned nucleus compared to control animals. However, 12 days post-surgery, the NMDA-induced loss of cholinergic neurons, as well as the decrease of their acetylcholinesterase -positive fibre projections in the cortex, were less in ACTH-(4-9) animals. Our data indicate that the early developmental effects of ACTH-(4-9) influence intrinsic neuroprotective mechanisms and reactivity of neuronal and glial cells, thereby resulting in a facilitated rescuing mechanism following excitotoxic injury.

Phenotypic Knockout of Nerve Growth Factor in Adult Transgenic Mice Reveals Severe Deficits in Basal Forebrain Cholinergic Neurons, Cell Death in the Spleen, and Skeletal Muscle Dystrophy

The disruption of the nerve growth factor (NGF) gene in transgenic mice leads to a lethal phenotype (Crowley et al., 1994) and hinders the study of NGF functions in the adult. In this study the phenotypic knockout of NGF in adult mice was achieved by expressing transgenic anti-NGF antibodies, under the control of the human cytomegalovirus promoter. In adult mice, antibody levels are 2000-fold higher than in newborns. Classical NGF targets, including sympathetic and sensory neurons, are severely affected. In the CNS, basal forebrain and hippocampal cholinergic neurons are not affected in the early postnatal period, whereas they are greatly reduced in the adult (55 and 62% reduction, respectively). Adult mice show a reduced ability in spatial learning behavioral tasks. Adult, but not neonatal, transgenic mice further show a new phenotype at the level of peripheral tissues, such as apoptosis in the spleen and dystrophy of skeletal muscles. The analysis of this novel comprehensive transgenic model settles the controversial issue regarding the NGF dependence of cholinergic neurons in adult animals and reveals new NGF functions in adult non-neuronal tissues. The results demonstrate that the decreased availability of NGF in the adult causes phenotypic effects via processes that are at least partially distinct from early developmental effects of NGF deprivation.

The ontogeny of behavioral sensitization to phencyclidine

Repeated exposure of adult rats to a variety of psychoactive compounds can result in altered behavioral responsiveness to later exposures depending on the dose, route, and frequency of administration and time of testing. The ontogeny and mechanism of this altered responsiveness are not well understood. To determine when behavioral sensitization to phencyclidine (PCP) occurs, neonatal and early developmental exposure effects of PCP were assessed on later behavioral responsiveness to a PCP challenge. Rat pups were injected daily for nine days beginning on either postnatal days (PNDs) 1 or 22 with 0.9% saline, 5.0 or 10.0 mg/kg PCP-HCl (s.c.). Ten days following the last injection, rats were given one of the following drug challenges: 0.9% saline, 5.0 or 10.0 mg/kg PCP-HCl (s.c.). Locomotor activity, ataxia, and several other behaviors were measured for 1 h beginning 2–3 min after the challenge injection. Two major findings emerged from these studies. First, pups treated subchronically with PCP on PNDs 1–9 did not exhibit any difference in behavioral sensitivity to a PCP challenge when tested on PND 19 compared to subchronically treated saline controls. In contrast, pups subchronically treated with PCP on PNDs 22–30 exhibited an increased sensitivity to the behavioral effects of a PCP challenge. These data suggest that PCP has age-dependent exposure effects that occur sometime after the first postnatal week and that result in an enhanced behavioral responsiveness to PCP later in life.

Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichloroethene on later development

Determining whether early developmental effects of perinatal exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE) persist. Cohort followed from birth; ages now 5 1/2 to 10 1/2 years. General community. Volunteer sample of 859 children, of whom 712 had been examined with the McCarthy Scales of Children's Abilities at 3, 4, or 5 years; 506 sent report cards. None. Neither transplacental nor breast-feeding exposure to PCBs or DDE affected McCarthy scores at 3, 4, or 5 years. There was no statistically significant relationship between poorer grades and PCB or DDE exposure by either route. The deficits seen in these children on the Bayley Scales of Infant Development through 2 years of age are no longer apparent.

Adult Children of Alcoholics A Valid Diagnostic Group?

"Adult children of alcoholics" (COAs) has become a popular diagnostic categorization denoting a group of adults sharing a common environmental background. These individuals are felt to share common familial effects of early development in an "alcoholic" home. The COA concept has gained significant acceptance in the popular press with many substance abuse treatment centers developing programmed treatment approaches for Adult COAs. However, little research evidence is available to validate this diagnosis. To evaluate the validity of the Adult COA concept among patients in treatment for substance abuse, we compared a series of patients for a variety of demographic, personality, psychiatric illness, and substance abuse phenomenology measures. The results of this comparison showed few distinctions in phenomenology between the two groups. The COA group reported more specific problem-drinking behaviors and medical problems related to alcohol as well as a higher total alcoholism severity score. This study finds only limited support for the validity of the diagnosis of Adult COA in a distinct inpatient substance abuse population.

DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9

Formation of anterior structures in the Drosophila embryo requires the product of the gene bicoid. The bicoid protein contains a homeodomain and may exert its effects in early development by regulating transcription of the gap gene, hunchback (hb). Consistent with this view, we have demonstrated that DNA-bound Bicoid fusion proteins stimulate gene expression. We used the gene activation phenotype in yeast to study DNA recognition by the Bicoid homeodomain. We found that a single amino acid replacement at position 9 of the recognition helix was sufficient to switch the DNA specificity of the Bicoid protein. The altered specificity Bicoid mutants recognized DNA sites bound by Ultrabithorax, fushi tarazu, and other related homeodomain proteins. Our results suggest that DNA specificity in Bicoid and Antennapedia class proteins is determined by recognition helix residue 9.

Maternal effects in early development.

Maternal effects in early development.

Early Developmental Effects of Lime-Neutralized Iron Hydroxide Suspensions on Brook Trout and Coho Salmon

Abstract A study of the effect of lime-neutralized iron hydroxide suspensions on eggs and alevins of brook trout (Salvelinus fontinalis) and coho salmon (Oncorhynchus kisutch) was conducted with a modified proportional diluter. Effects were interpreted from data on hatchability, survival, and growth in five test concentrations and control. Growth of 90-day-old coho salmon alevins was reduced in water containing 1.27 mg Fe/liter of lime-neutralized suspended iron, whereas hatchability was unaffected in the highest concentration tested, 10.5 mg Fe/liter, However, 10.5 mg Fe/liter water had no measurable effect on hatchability, survival, and growth of brook trout alevins. The safe upper limit of lime-neutralized suspended iron for hatchability, survival, and growth of coho salmon alevins may lie between 0.97 and 1.27 mg Fe/liter.

Net uptake of glucose, glycerol, and fatty acids by the isolated perfused rat lung.

Net uptake of glucose, glycerol, and fatty acids by the isolated perfused rat lung.

Genetic control of cellular differentiation in Ulva mutabilis. Gene effects in early development

The spontaneous mutant bu (bubble) of the multicellular green alga Ulva mutabilis develops in its most extreme form as a hollow sphere consisting of only one cell type, while the wild type has a differentiated thallus consisting of rhizoid cells, giant stem cells, and blade cells. In the early development of the wild type, the planes of division are perpendicular to the long axis of the plant. Later, the restrictions of the division planes are partly released and the planes are perpendicular to the surface of the plant and otherwise arbitrarily oriented. The mutant, throughout its development, has only the latter restrictions on its division planes. The early cell divisions of the mutant are synchronized in a diurnal light-dark cycle, in contrast to the early development of the wild type, but in agreement with what is found in its blade. In addition, newly differentiated blade cells, when isolated, develop into plants phenotypically similar to the mutant. These results suggest that the mutant cells are equivalent to the blade cells of wild type. The bu gametophytes derived from bu + bu sporophytes may develop either their own bubble phenotype, or phenotypes intermediate between bubble and wild type, or the wild-type phenotype. The frequency of the latter is lower by treatment of the spore mother cells with dactinomycin during a period immediately preceding meiosis and sporulation. It is also dependent on the length of the first period of light to which the zoospores are exposed. Accordingly, it is a premeiotic transcription of the bu + gene, and a product of the gene is transferred from the heterozygous ( bu + bu ) spore mother cells to the zoospores. When the zoospores are exposed to light for the first time, the bu + gene product becomes involved in processes which proceed during the light-dark sensitive period, and when completed, channel the development of the mutant progeny into the developmental path of the wild type. The predetermining effect of the bu + product is also observed among gametophytes derived from sporophytes heterozygous for bu and the semidominant mutant Sl (Slender). The presence of Sl in the heterozygous sporophyte has no effect on predetermination, even if Sl is phenotypically expressed in the heterozygote itself. But the presence of Sl in the zoospores reduces the expression of the predetermination, and this implies that the Sl + gene is of importance for the completion of the bu + processes of the zoospores. The blade cells form the reproductive units (zoospores and gametes) in Ulva, and the properties of the mutant can be explained if the bu + gene is concerned with the removal of restrictions imposed on the differentiated blade cells, so that the total information in the genome can again be used to direct a normal development.