Search PubMed⌕ Search

Biomedical subjects

F E Bloom

Publications and source records attributed to F E Bloom.

At least 163 records · Page 9Linked to original sources
PubMed1988

Viral infection of neurons can depress neurotransmitter mRNA levels without histologic injury.

Neonatal mice inoculated with lymphocytic choriomeningitis virus (LCMV) have non-lytic persistent neuronal infection and disturbed behavior. We now show that LCMV replicates in neurons containing the neurotransmitter somatostatin without morphologic evidence of injury and that persistent neuronal LCMV infection in mice is attended by a decrease in brain levels of somatostatin mRNA. Brain levels of mRNA for another neurotransmitter peptide, cholecystokinin, are not decreased. These data are the first to localize a virus to a specific neurotransmitter-containing cell during in vivo infection and suggest that persistent viral infections could cause neurologic or psychiatric diseases through selective effects on brain levels of neurotransmitter mRNAs.

Animals↗
PubMed1988

Development of somatostatin-containing neurons and fibers in the rat hippocampus.

Using a combination of in situ hybridization and immunohistochemistry, the development of somatostatin (SS)-containing neurons and fibers was examined in the rat dorsal hippocampus and dentate gyrus. The major development of this hippocampal peptidergic system occurs postnatally. At postnatal day 1 (P1), neurons containing SS mRNA are evident primarily in the stratum oriens, but also in the hilus of the dentate gyrus. Similar neurons are also immunoreactive for SS28 and SS28(1-12), suggesting a minimal lag in the transcription of SS mRNA and its translation into specific SS peptides. The number of SS neurons increases postnatally to P10, followed by a decrease in number in the adult. This transient change in the number of SS neurons coincides with dramatic changes in SS28(1-12)-immunoreactive fibers, which are initially present in the stratum lacunosum moleculare, with no significant immunoreactivity in the dentate gyrus. By P15, the molecular layer of the dentate gyrus is densely innervated, while similar immunoreactivity in the stratum lacunosum moleculare is greatly reduced. These data are consistent with a transient projection from the stratum oriens to the stratum lacunosum moleculare, which is replaced by a projection from the hilus to the molecular layer of the dentate gyrus as this structure matures.

Animals↗
PubMed1988

Immunohistochemical and in situ hybridization analysis of the development of the rat somatostatin-containing neocortical neuronal system.

The chemical differentiation of somatostatin (SS) neurons in rat neocortex was characterized by molecular biochemical and morphological methods. Northern (RNA) blotting indicates that regional distribution of SS mRNA correlates with the known distribution patterns of SS-containing neurons in the adult, while similar analysis of poly (A)+ RNA isolated from telencephalon at various times postnatally shows an increase between P9 and P15, with a slight decrease in the adult. In situ hybridization with a probe specific to SS mRNA, and immunohistochemistry using antisera specific for the N-terminally extended form of SS, SS28, and SS28(1-12), were used to detect neocortical neurons containing this mRNA or its translation product. The appearance of SS mRNA is coincident with detectable immunoreactivity for SS peptides. The expression of the SS gene by cortical neurons occurs in two waves. From P1 to P11, hybridizing neurons are predominant below the cortical plate in the developing infragranular layers. Immunohistochemical analysis of immunoreactivity to SS28 reveals a significant development of this neocortical system by late gestation (E20). At this point SS28(1-12), the predominant SS form detected, is mainly in neurons of the subplate, with less detectable immunoreactivity in the intermediate zone and cortical plate. By P2, neurons in the subplate exhibit detectable SS28 and SS28(1-12). Although immunoreactive perikarya are no longer detectable at P2 in the cortical plate or marginal zone, a very dense plexus of SS28(1-12) fibers is seen in the subplate, marginal zone, and intermediate zone; relatively few immunoreactive fibers are found in the cortical plate. By P12, a dramatic shift occurs; a large supragranular population of these SS neurons is observed by both mRNA and antibody methods, as is a subsequent decrease in number in the adult. The shift in immunoreactivity occurs with supragranular SS28-containing neurons now prominent, and SS28(1-12)-containing neurons and fibers greatly diminished. The number of neurons containing SS mRNA or SS28 immunoreactivity decreases from P12 to adult, when these neurons exhibit a bilaminar distribution. Neurons immunoreactive for SS28(1-12) are now sparsely distributed throughout the cortex, while SS28(1-12) fibers densely innervate layers I and V/VI.

Age Factors↗
PubMed1988

Systemic phenoxybenzamine but not beta-adrenergic antagonists block noradrenergic inhibition of cerebellar Purkinje and hippocampal pyramidal neurons.

Previous pharmacological characterization of central noradrenergic receptors has been interpreted as favoring beta-type receptors on cerebellar Purkinje neurons and hippocampal pyramidal neurons. However, the recent development of additional noradrenergic antagonists suitable for single neuron analysis, prompted an initial re-evaluation of alpha and beta adrenergic receptors in these two cell populations. In contrast with earlier data based on local antagonism of iontophoretric or synaptically released norepinephrine (NE), we now find that systemic phenoxybenzamine, the alpha antagonist, was effective in blocking responses to NE in cerebellum and hippocampus, whereas systemic beta antagonists metoprolol, ICI 118.551 [correction of ICI 181.551], or proprandol did not interfere with local NE responses at systemic doses that altered spontaneous discharge rates. These preliminary data suggest that a more complete re-evaluation of the nature of central noradrenergic response mechanisms may be warranted.

Adrenergic beta-Antagonists↗
PubMed1988

Neurotransmitters: past, present, and future directions.

As originally conceived, central neurotransmitters operated uniformly, exciting or inhibiting postsynaptic targets by receptors that activated passive ionic conductances. As the list of transmitter substances and their actions expanded, concepts of transmitter actions have broadened and grown more complex to include a variety of intramembranous and intracytoplasmic second messengers that can regulate both active and passive ionic conductances. Present-day research directions center on further expansion of the lists of identified transmitter candidates, and on the more precise characterization of their sites and mechanisms of receptor regulation and transduction. Current research is also illuminating the means by which neurotransmitters act in a coordinated fashion to regulate common synaptic targets. Future directions will likely include new forms of interneuronal, intraneuronal, and glial signals, including lipids, steroids, and as-yet-undiscovered superfamilies of peptides and receptors. Although recent advances in understanding specific transmitters have been achieved largely through in vitro electrophysiological analyses, it is hoped that future research will recast these events in the context of the intact functioning brain. Neurotransmitters are likely to remain a productive focus of future research.

Animals↗
PubMed1988

P300 and the risk for alcoholism: family history, task difficulty, and gender.

P300 event-related brain potentials (ERPs) were obtained from 20 pairs of male and 20 pairs of female undergraduate subjects. One member of each pair reported having a father who was alcoholic (FHP), the other reported no known alcoholic biological relative (FHN). Pair members were matched on age, height, weight, grade point average, and personal drinking history. Three auditory tasks which differed in stimulus discrimination difficulty were presented to each subject. All tasks employed 20% target and 80% standard tones with the subject required to move their index finger whenever a target stimulus was detected. No significant differences in P300 amplitude or latency were obtained between the family history subject groups, although female FHP subjects tended to have smaller P300 amplitudes than their FHN counterparts. P300 amplitude decreased with increases in the amount of self-reported alcohol consumed for FHP subjects but significantly so only for the most difficult task situation. The results suggest that the relationship between the P300 ERP and the inheritability of alcoholism is not yet clear and may be subject to modulation by task requirements, population differences, and subject sex.

Adolescent↗
PubMed1988

Event-related brain potentials in individuals at high and low risk for developing alcoholism: failure to replicate.

Event-related brain potentials (ERPs) were used to compare young men having a positive paternal family history for alcoholism (FHP) with carefully matched control subjects having no family history for alcoholism (FHN). The P300 ERP component was obtained from all subjects (n = 10/group) with a complex auditory paradigm before and on two occasions after they received a placebo drink which they were told might contain alcohol. The procedures employed replicated those of a previous study in which FHP subjects showed diminished P300 potentials compared to FHN subjects under the placebo as well as ethanol consumption conditions--a finding which raised the possibility that the P300 ERP component might be a biological marker for subjects at high risk to develop alcoholism. No differences between the family history groups were obtained for the P300 or any other ERP component using the replication procedures. Both groups demonstrated a decrease in P300 amplitude across trial blocks in a similar fashion suggesting that habituation effects may have diminished the ERP response.

Adult↗
PubMed1988

Bedtime ethanol increases resistance of upper airways and produces sleep apneas in asymptomatic snorers.

Nasal continuous positive airway pressure (nasal CPAP) and polysomnography were used to analyze the time course of the effect of bedtime ethanol on resistance of upper airways and on the number of respiratory pauses during sleep. On one night, six asymptomatic nonalcoholic male snorers drank 2 ml/kg of 100 proof vodka mixed in orange juice (ethanol dose, 0.79 gm/kg, giving a peak blood alcohol level of 71.8 +/- 33.3 mg/dl). On a second night they received a placebo (1-2 drops of vodka floated on top of the orange juice). We measured (a) the minimum nasal (CPAP) required to eliminate snoring, (b) the number of hypopneas and apneas during each hour of sleep and (c) the arterial oxygen saturation (SaO2) by ear oximetry. On the alcohol night there was a significant increase in the CPAP pressure required to eliminate snoring (placebo 4.8 +/- 1.7 cm H2O, alcohol 6.2 +/- 1.5 cm H2O). The number of respiratory events per hour of sleep (apnea index) was 7.5 +/- 2.1 for ethanol nights versus 3.8 +/- 2.7 for placebo nights (p less than 0.0125). An apnea index of greater than 5 is generally considered abnormal. There was no significant difference in the number of desaturation events (declines of 4% or more in the SaO2) or in the mean SaO2, but the minimum SaO2 was significantly lower on the ethanol night (placebo 89.8% +/- 1.6, alcohol 86.8% +/- 2.7, p less than 0.05). The effect of this dose of alcohol on airway resistance was most pronounced during the first 2 hr after ingestion.

Adult↗
PubMed1988

Assessment of young men at risk for alcoholism with P300 from a visual discrimination task.

A visual discrimination paradigm was used to elicit the P3 (P300) component of the event-related brain potential (ERP) in a large group (N = 196) of male undergraduate volunteers. Comparison of P3 amplitude and latencies between individuals with a positive family history for alcoholism (FH +) and those without such a history (FH -) obtained no differences between the groups. No associations between P3 latency or amplitude and the amount of alcohol typically consumed were found. Differences between the present and previous P3 family history studies using visual stimuli are attributed to the cognitive demands of ERP task.

Adult↗
PubMed1987

Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus.

Intraperitoneal injection of ethanol (2 g/kg) substantially augmented recurrent inhibition in the dentate gyrus, as measured by population responses to paired-pulse stimulation of the perforant path. In contrast, this dose of ethanol had no significant effect on singly evoked (or conditioning) population spikes. These data indicate that the increased recurrent inhibition by ethanol was not due to a generalized depressant effect, and suggests that at these doses and time points ethanol can selectively alter synaptic transmission in the hippocampus.

Action Potentials↗
PubMed1987

Rewarding properties of beta-endorphin as measured by conditioned place preference.

The role of beta-endorphin as a possible mediator in the reinforcing properties of opiates was investigated using a conditioned place preference paradigm. Heroin, a synthetic opiate known to have reinforcing properties, produced a strong preference for an environment previously paired with heroin injection at all doses tested (0.25, 0.5, 1.0, 2.0 mg/kg SC). No such place preference was observed following saline injections. Rats also showed dose-dependent place preference for the environment paired with beta-endorphin when injected intracerebroventricularly (significant dose was 2.5 micrograms). At higher doses (5.0 and 10.0 micrograms) rats showed no preference for the paired environment, but were catatonic. Pretreatment with naloxone (0.04, 0.2, 1.0 mg/kg SC) attenuated the rewarding effect of beta-endorphin (2.5 micrograms) at all doses tested. The lowest dose of naloxone which had no aversive effect when tested alone could also significantly block the positive effect of beta-endorphin. The reinforcing dose of beta-endorphin (2.5 micrograms) also produced an increase in locomotor activity, when tested in photocell cages. This suggests that the hyperactivity induced by beta-endorphin may contribute to the preference for an environment previously paired with the same drug. The reinforcing effect of beta-endorphin is most probably mediated by the mu and/or delta opioid subtype receptor, since beta-endorphin has a high affinity for these receptors. These results demonstrate positive reinforcing properties of beta-endorphin in the central nervous system.

Animals↗
PubMed1987

Subtractive cloning of complementary DNAs and analysis of messenger RNAs with regional heterogeneous distributions in primate cortex.

Morphological heterogeneity of individual neurons in the mammalian brain must ultimately result from differences between cells in their profiles of gene expression. However, the degree to which neurons located in different regions of the brain express different sets of genes is not known. Using differential cDNA cloning procedures, including subtractive hybridization and differential colony screening, a quantitative analysis of RNAs with heterogeneous distributions in the telencephalon of the rat and Old World monkey has been performed. The results suggest that no species of RNA exist with a distribution specific to the hippocampus or neocortex of the rat with an abundance greater than 0.05%. Additionally, the results with an abundance of 0.05% or greater which is present in neocortex of the monkey but absent from the cerebellum suggest that only one species of mRNA exists. A Northern blot analysis of cDNA clones representing mRNAs present in the neocortex but absent from the cerebellum of the monkey is presented, establishing the effectiveness of subtractive hybridization between different regions of the brain for cDNA cloning. Also presented is in situ hybridization analysis of the cellular distributions in primate neocortex of two mRNAs. One of these RNAs, detected by clone 1B4 is present in cortical laminae V and VI, and exhibits a high degree of heterogeneity in the overall density of labelled cells.

Animals↗
PubMed1987

Hypertonic saline mimics the effects of vasopressin on inhibitory avoidance in the rat.

Rats tested in a step-through inhibitory avoidance task were administered hypertonic saline (2 ml of 0.25. 0.5, and 1.0 M intraperitoneally) or arginine vasopressin (1.0, 2.0, and 4.0 micrograms) injected subcutaneously (sc) after the training trial where the rats received a mild footshock (0.2 mA, 3 s). Both hypertonic saline and vasopressin produced significant increases in latency to reenter 24 h later. These treatments failed to increase reentry latencies in animals that received the same procedure but no shock. The facilitation of inhibitory avoidance produced by hypertonic saline was reversed by sc administration of 25 micrograms of the vasopressor (V-1) vasopressin antagonist, dPtyr(Me)AVP. The results suggest that the endogenous release of vasopressin can be behaviorally significant in situations of acute homeostatic challenge.

Animals↗
PubMed1987

Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing.

The structures of two rat brain-specific 1B236 mRNAs, alternative splice products from a single gene regulated differently during postnatal brain development, were deduced from full-length cDNA clones. The 626- and 582-amino acid-long encoded proteins are indistinguishable from two forms of myelin-associated glycoprotein, a cell adhesion molecule involved in axonal-glial and glial-glial interactions in postnatal brain development, particularly in myelination. The two proteins share a single membrane-spanning domain and a glycosylated N terminus but differ in the structures of their C termini. The N terminus consists of five domains related in sequence to each other and to immunoglobulin-like molecules, especially the neural cell adhesion molecule N-CAM, suggesting a common structure for cell adhesion molecules.

Aging↗
PubMed1987

Splice site selection in the proteolipid protein (PLP) gene transcript and primary structure of the DM-20 protein of central nervous system myelin.

Proteolipid protein (PLP) is the major myelin membrane protein of the central nervous system. We have isolated a copy of an alternatively spliced PLP gene transcript from a mouse brain cDNA library that was screened for PLP-related sequences. The encoded 241-amino acid protein differs from PLP by an internal deletion of 35-amino acid residues (116-150) from the major hydrophilic domain. This PLP variant is identical with the DM-20 protein of myelin, previously described as a brain-specific myelin component and known to be related to PLP. We determined the corresponding nucleotide sequence of the rat PLP gene and found that DM-20 mRNA results when a second 5' splice site, located 105 nucleotides within the third exon of the primary PLP transcript, is utilized in precursor mRNA (pre-mRNA) splicing. This demonstrates that alternative 5' splice site selection can determine the protein product of a cellular gene. DM-20 mRNA is expressed in rat brain with approximately 50% abundance relative to PLP mRNA and appears to be developmentally coregulated.

Amino Acid Sequence↗
PubMed1987

Isotypes of alpha-tubulin are differentially regulated during neuronal maturation.

The mRNAs for two isotypes of alpha-tubulin, termed T alpha 1 and T26, are known to be expressed in the rat nervous system. We have compared the expression of these two alpha-tubulin mRNAs during neural development, using RNA blotting and in situ hybridization techniques with probes directed against unique sequences of each mRNA. T alpha 1 mRNA is highly enriched in the embryonic nervous system but is markedly less abundant in the adult brain; T26 mRNA is expressed in many embryonic tissues with little change in abundance during development. Within the nervous system, T alpha 1 mRNA is enriched in regions with neurons actively undergoing neurite extension, such as the cortical plate, whereas T26 mRNA is relatively homogeneous in distribution, with some enrichment in proliferative zones. Expression of T alpha 1 mRNA is also increased in PC12 cells induced to differentiate and extend neurite processes by nerve growth factor. Taken together, the data indicate that T alpha 1-tubulin mRNA is expressed at high levels during the extension of neuronal processes. The abundant expression of T alpha 1-tubulin mRNA may therefore reflect either a means to increase the available pool of alpha-tubulin or a specific requirement for the T alpha 1 isotype for neurite extension.

Cell Differentiation↗