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Biomedical subjects

C Pilgrim

Publications and source records attributed to C Pilgrim.

At least 19 recordsLinked to original sources
PubMed2001

Clustering in artificial categories: an equivalence analysis.

Category clustering is a robust finding in the free recall of familiar category members, but has rarely been studied with artificial categories. In the present study, college students learned artificial categories via stimulus-equivalence methodology. Arbitrary match-to-sample training with nonsense syllables established three interrelated conditional discriminations, and, for most subjects, unreinforced test trials revealed the emergent stimulus-control relations considered to be evidence of equivalence classes. Free-recall tests revealed evidence of significant within-class clustering both before and after equivalence testing, but was more pronounced after the equivalence tests. These findings confirm that classic phenomena like clustering in free recall can be studied with stimulus-equivalence methodology, thus allowing for experimental control over relevant variables.

Adult↗
PubMed2000

Developmental regulation of glutamic acid decarboxylase mRNA expression and splicing in the rat striatum by dopamine.

Dopamine (DA) promotes the morphological differentiation of striatal GABAergic neurons through D(1) receptor activation and cAMP/PKA signaling. In this study, we investigated the developmental role of DA on the expression of the two GAD(65/67) genes and the alternative splicing of GAD(67) transcripts in the rat striatum. In vivo, embryonic and adult GAD(67) splice variants and GAD(65) transcripts increased until E17 and E19, respectively. Thereafter, the embryonic GAD(67) isoform disappeared, whereas GAD(65) mRNA levels remained unchanged postnatally. The hypothesis that the prenatal ingrowth and functional maturation of nigrostriatal afferents may be responsible for these developmental events through DA-dependent signaling pathways was tested in E17 rat striatal cultures. Treatment with DA and D(1) but not D(2) agonists decreased the ratio of embryonic to adult GAD(67) mRNAs and increased GAD(65) mRNA levels as well as GABA synthesis rates. Our findings demonstrate a distinct developmental switch in the regulation of GAD(65) expression and GAD(67) splicing in the rat striatum which clearly depends upon D(1) receptor but not D(2) signaling. The dopaminergic input thus appears to control the functional differentiation of GABAergic neurons not only by upregulation of expression of the two GAD genes but also by regulating GAD(67) splicing.

Aging↗
PubMed2000

Developmental profile of Sry transcripts in mouse brain.

Transient activation of the gene Sry in the gonadal ridge during a brief period of embryonic development is believed to function as a key signal for sex determination. However, a number of reports suggest that Sry expression is not as restricted in space and time as one would expect if its role was confined to directing male-specific differentiation in the early gonadal anlage. We have previously reported the occurrence of Sry/SRY transcripts in adult murine and human brain. The present communication is concerned with the study of the ontogenetic time course of Sry transcripts in mouse brain as detected by reverse transcription-polymerase chain reaction (RT-PCR). Particular emphasis was placed on the identification of two different forms of Sry mRNA, which can be linear or circular. To this aim, we used specific RT-PCR strategies to distinguish between both. Sry transcripts were found in male brain tissue of all ontogenetic stages investigated. Circular, presumably untranslatable, transcripts were found in embryonic brains of day 11 through 19. In contrast, postnatal Sry transcripts were linear, and thus translatable, and were found in diencephalon, midbrain, and cortex. The change from one transcript form to the other suggests that expression of the Sry gene in mouse brain is developmentally regulated, presumably by a switch in promoter selection. This supports the notion that Sry expression in brain is biologically significant.

Adult↗
PubMed2000

Acquisition of arbitrary conditional discriminations by young normally developing children.

Three experiments investigated conditions designed to facilitate acquisition of arbitrary conditional discriminations in 3- to 6-year-old normally developing children. In Experiment 1, 6 subjects failed to master the arbitrary match-to-sample task under conditions of differential reinforcement alone, but 7 subjects did so when instructions or instructions and sample naming were added. In Experiment 2, sample naming introduced in a blocked-trial arrangement resulted in acquisition, but only when the sample name was a nonsense syllable provided by the experimenter (5 of 7 subjects) and not when the sample name was generated by the subject (0 of 5 subjects). Experiment 3 demonstrated the effectiveness of a training sequence involving thematically related stimuli as an intermediate step facilitating the transition from identity to novel arbitrary relations. The difficulties in mastering arbitrary conditional discriminations shown here imply that further analyses with young children will be particularly important in efforts to investigate the development of theoretically important stimulus relations.

Child↗
PubMed2000

Evaluation of a family-based substance abuse prevention program targeted for the middle school years.

A family-based substance abuse prevention program was evaluated which emphasizes family cohesion, school and peer attachment, self-esteem, and attitudes about adolescent use of alcohol and tobacco. The program was implemented in rural communities and targeted families with students entering middle or junior high school. Baseline surveys were conducted with students and parents in four schools and were readministered one year later. Because the program was voluntary, a quasi-experimental design was used to compare participants (29 students and 28 parents) and nonparticipants (268 students and 134 parents). Analyses of covariance indicated that student participants, as compared to nonparticipants, had higher family cohesion, less family fighting, greater school attachment, higher self-esteem, and believed that alcohol should be consumed at an older age at the one year follow-up. There were fewer significant results for parent participants. Strategies for involving parents in prevention programs are discussed.

Adolescent↗
PubMed1998

Differentiative effects of dopamine on striatal neurons involve stimulation of the cAMP/PKA pathway.

The neurotransmitter dopamine (DA) stimulates neurite outgrowth and growth cone formation in cultures of embryonic rat striatum through activation of D1 but not D2 receptors. We show here that neurite outgrowth could be stimulated to a similar extent by elevating cellular cAMP levels. Second, the neuritotrophic effect of DA was completely abolished by inhibiting adenylate cyclase or protein kinase A (PKA) but not protein kinase C (PKC). Third, double staining of cultures with antibodies against growth-associated protein-43 (GAP-43) and the phosphorylated form of the cAMP response element binding protein (pCREB) showed that pCREB was nearly exclusively associated with GAP-43-positive, i.e., actively growing, neurons. Again, this effect depended on D1 receptor and PKA activation. Although cross-talk with other signaling pathways needs to be studied further, we conclude that DA promotes the differentiation of striatal neurons via stimulation of D1 receptors and the cAMP/PKA signal transduction pathway.

Animals↗
PubMed1998

Mapping of D1 dopamine receptor mRNA by non-radioactive in situ hybridization.

In order to improve the identification and characterization of dopaminoceptive neurons, the rat brain was mapped for D1 dopamine receptor mRNA by non-radioactive in situ hybridization (ISH) with a 45mer digoxigenin-labeled oligonucleotide probe. The specificity of the results was controlled with the help of a 396-bp D1 receptor riboprobe. Labeled hybrids were visualized with an alkaline phosphatase-coupled anti-digoxigenin antibody. The high resolution obtained permitted individual labeled cells to be identified and to distinction between cell bodies and processes. D1 mRNA was largely confined to neurons. With the exception of ependymal cells, glial cells were not distinctly labeled. Subcellularly, D1 mRNA was localized to perikarya but not to dendrites or axons. D1 receptor-expressing neurons were present in all of the known terminal fields of mesencephalic or diencephalic dopaminergic neurons. However, D1 message was also detected in brain areas which are not known to contain D1 ligand binding sites or in which the presence or the cellular source of this receptor subtype had previously not been unequivocally established, such as the hippocampus or cerebellar cortex. Moreover, labeled neurons were present in regions not known to receive dopaminergic projections, such as the thalamic and some brainstem nuclei. We conclude that this ISH technique provides a considerable gain in sensitivity and resolution with regard to neurotransmitter receptor mapping.

Animals↗
PubMed1998

The Y-chromosomal genes SRY and ZFY are transcribed in adult human brain.

Sexual differentiation of the brain is thought to be regulated by hormonal signals from the developing male gonad. However, more-recent experimental and clinical data throw some doubt on the general validity of the "classical" steroid hypothesis and suggest that additional intervening factors or mechanisms need to be considered. In particular, it is now envisaged that neurons are capable of acquiring sex-specific properties independently of their hormonal environment. Here we show that two Y-chromosomal genes involved in sex determination of the gonad, SRY and ZFY, are transcribed in hypothalamus, and frontal and temporal cortex of the adult male human brain. These genes are candidates for male-specific transcriptional regulators that could confer upon human brain cells the potential for hormone-independent realization and maintenance of genetic sex.

Aged↗
PubMed1997

Localization of D1 and D2 dopamine receptors in the rat mesencephalic trigeminal nucleus by immunocytochemistry and in situ hybridization.

The rat mesencephalic trigeminal nucleus (MTN) receives a dopaminergic innervation. In order to identify and localize dopaminoceptive cells within this nucleus, expression of D1 and D2 dopamine (DA) receptors was examined by immunocytochemistry with subtype-specific antibodies and in situ hybridization with digoxigenin-labeled cRNA probes. Immunocytochemical labeling was restricted to neuronal perikarya and proximal processes whereas the hybridization signal was confined to MTN cell bodies. Cells immunopositive for D1 were located throughout the entire MTN whereas cells labeled with D2 antibodies were concentrated in its caudal portion. D1 receptor message was found in relatively low levels. In contrast, high levels of mRNA for D2 were seen in MTN neurons. The distribution of DA receptor mRNA-containing cells were very similar to those of DA receptor immunoreactivity. Neurons expressing the D1 receptor gene were localized in both rostral and caudal portions, which receive inputs from masticatory muscle spindles and from spindles and periodontal ligament receptors, respectively. D2 receptors were limited to ventrocaudally located cells. These results suggest that processing of proprioceptive information in the MTN is controlled by the DAergic input through different postsynaptic mechanisms.

Animals↗
PubMed1997

Close friend and group influence on adolescent cigarette smoking and alcohol use.

The relative influence of adolescents closest friends and their friendship group on their cigarette smoking and alcohol use was investigated in a short-term, longitudinal study of 1,028 students in the 6th, 8th, and 10th grades in 2 school systems. The amount of influence over the school year was modest in magnitude and came from the closest friend for initiation of cigarette and alcohol use. Only the friendship group use predicted transition into current cigarette use, whereas only the close friend use predicted transition into current alcohol use. Both group and close friends independently contributed to the prediction of adolescents' drinking to intoxication. No difference in the amount of influence, was found between stable and unstable close friendships or friendship groups; neither grade nor gender of the adolescents related to the amount of influence.

Adolescent↗
PubMed1996

Pre- and postnatal development of dopaminergic neuron numbers in the male and female mouse midbrain.

Quantitative information about dopaminergic neuron numbers in the mesencephalon is needed to assess the significance of physiological cell death in the regulation of the development of this neural system. Therefore, stereological techniques were applied to determine absolute numbers of mesencephalic neurons immunoreactive to tyrosine hydroxylase during the ontogenetic period between embryonic day (E) 13 and postnatal day (P) 90. Male and female CBA/J mice were examined separately. The most rapid development with a 2.5-fold increase of total counts of immunostained cells per midbrain took place in the prenatal period. Beginning at E21, immunostained cells were counted separately in their three main locations, substantia nigra (SN), ventral tegmental area (VTA), and retrorubral field (RRF). Neuron numbers in RRF and VTA reached adult levels perinatally. In contrast, counts of immunostained cells in SN continued to increase postnatally. The only sign of cell loss was a transient decrease in VTA cell numbers (but not in total numbers of immunostained midbrain neurons) between E21 and P14. There were no statistically significant sex differences in cell numbers at any time point investigated. It is concluded that physiological cell death is not a major factor in the developmental regulation of dopaminergic cell numbers in the mouse midbrain.

Animals↗
PubMed1996

Genotype-dependent sex differentiation of dopaminergic neurons in primary cultures of embryonic mouse brain.

In order to investigate genetic factors that interfere with hormone-mediated sex differentiation of dopaminergic neurons, we raised sex-specific primary cultures from embryonic day 13 diencephalon (D) or mesencephalon (M) of three different strains of mice, NMRI, CBA/J, and BALBc/J. Part of the cultures were maintained for 6 or 13 days in vitro (DIV) in medium containing 17 beta-estradiol or testosterone. The cultures were analyzed for sex differences in numbers of tyrosine hydroxylase-immunoreactive neurons, endogenous dopamine (DA) levels, and specific uptake of [3H]DA. Previous results obtained with cultures of embryonic Sprague-Dawley rats had shown that these parameters develop sex-specific characteristics in the absence of sex differences in hormone environment. Similar steroid-independent sex differences as they occur in the rat were found in M cultures of NMRI but not in CBA and BALBc mice. Long-term sex steroid treatment did not affect any of the above parameters in any strain. It is concluded that cell-autonomous realization of the genetic sex of dopaminergic neurons depends on the genetic background.

Analysis of Variance↗
PubMed1996

Activation of dopaminergic D1 receptors promotes morphogenesis of developing striatal neurons.

The early dopaminergic input from the midbrain may play an important role in the development of the basal ganglia. We therefore investigated whether and how dopamine affects the morphogenesis of striatal target neurons. Dissociated cell cultures of embryonic day 17 rat striatum were raised for seven days. Cells were then incubated with dopamine or various receptor-specific ligands for 1 h. At various times after termination of the treatment, cells were immunostained for growth-associated protein-43. Morphological parameters including numbers of growth cones, length of neurites, number of bifurcations, and neuronal soma size were assessed by means of a computer-based morphometric device. Treatment with dopamine in low concentrations as well as with the D1-like receptor agonist SKF 38393 increased the numbers of growth cones and neurite length and arborization. The morphogenetic effect took several hours to evolve and remained stable for at least 24 h. It could be blocked by the D1-like receptor antagonist SCH 23390 or by cycloheximide but not by pretreatment of the cultures with tetrodotoxin. The D2-like receptor agonist quinpirole had no effect on the morphological parameters and did not contribute to that of SKF 38393. Dopamine and SKF 38393 but not quinpirole also induced an increase in the number of neurons immunoreactive for Fos-like proteins. However, this effect was restricted to growth-associated protein-43-negative neurons. This is the first observation of a positive regulatory effect of D1-like receptors on neuronal morphogenesis. We conclude that the changes reflect true differentiation rather than short-term modulation of cellular properties and that c-fos induction is not an obligatory step in the transduction pathway coupling D1-like receptors to neurite outgrowth. Our results suggest that the differentiation of embryonic striatal neurons is promoted by the dopaminergic nigrostriatal projection through D1-like receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Sex differentiation of rat hippocampal GABAergic neurons.

In order to analyse mechanisms of sex differentiation of the hippocampus at the cellular level, the differentiation of hippocampal GABAergic neurons was studied in vitro. Serum-supplemented and serum-free dissociated cell cultures were raised from the hippocampus of embryonic day 17 male and female rat embryos for up to 14 days in vitro. This time period roughly corresponds to the critical phase for sex differentiation of the rat brain as determined in vivo. Serum-free cultures were treated with testosterone and/or 17 beta-oestradiol for the entire culture period. Control cultures from male donors contained twice as many GABA-immunoreactive neurons as those from female donors, while there was no sex difference in overall counts of neurons stained for microtubule-associated protein 5. Measurements of high-affinity uptake of [3H]GABA essentially confirmed this sex difference. The development of the sex difference could not be influenced by long-term treatment with androgen or oestrogen. It is concluded that sex differentiation of a specific subpopulation of hippocampal neurons may take place independently of the environment provided by gonadal steroids and in the absence of extrinsic connections with the hypothalamus or other relays of the limbic circuit.

Animals↗
PubMed1996

Birthdates of the tyrosine hydroxylase immunoreactive neurons in the hypothalamus of male and female rats.

This study determined the birthdates of the tyrosine hydroxylase-(TH) immunoreactive (IR) neurons in the zona incerta (ZI), periventricular nucleus (PeVN) and arcuate nucleus (AN) of male and female rats. 'Long-survival' [3H]thymidine autoradiography combined with TH immunocytochemistry, the first enzyme of catecholamine synthesis, was used. In males, TH-IR neurons originate in the ZI between embryonic days (E) 12 and 13, while in the PeVN and AN this process is prolonged until E16. The majority of TH-IR neurons became postmitotic at E12 in the ZI, between E12 and E14 in the PeVN and at E15 in the AN. The birthdate of TH-IR neurons was sexually dimorphic with (a) generation of the majority of TH-IR neurons in the ZI in males proceeding that in females, (b) generation of TH-IR neurons in the AN of males delayed as compared to females, and (c) average daily fractions of the newborn TH-IR neurons in each hypothalamic region of females exceeding that seen in males. This sexual dimorphism was observed prior to E16, i.e. before the onset of sex difference in androgen levels, implying a hormone-independent mechanism, determined at the genetic level.

Animals↗