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Biomedical subjects

F E Bloom

Publications and source records attributed to F E Bloom.

At least 37 records · Page 2Linked to original sources
PubMed1999

P300, alcoholism heritability, and stimulus modality.

The P300 event-related brain potential (ERP) was elicited with auditory and visual stimuli from members of 13 families who were at high risk (HR) for alcoholism (father diagnosed as alcoholic) and 13 families at low risk (LR) for alcoholism. Each family consisted of a father, mother, and at least two biological children. The intrafamily member correlations (father vs. child, mother vs. child, child vs. child) for P300 amplitude were obtained for 15 electrode sites. P300 amplitude from auditory stimuli was not correlated among HR family members, but was positively correlated among LR family members. P300 amplitude from visual stimuli was positively correlated among both HR and LR family members. When taken in conjunction with previous findings, the present results suggest that P300 amplitude from auditory stimuli may not be as reliable as ERPs from visual stimuli for the assessment of alcoholism heritability.

Adolescent↗
PubMed1998

Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord.

The cellular distribution of the type 3 serotonin receptor (5HT3R) in the rat brain was established immunocytochemically by using a polyclonal antibody raised against a synthetic peptide from the deduced amino-acid sequence of the cloned 5HT3R. The 5HT3R-immunoreactive neurons were found in the forebrain, brainstem, and spinal cord, but within each region, the intensity of the immunoreactivity differed considerably. Within the forebrain, intensely immunoreactive cells were found in layers II-III of the neocortex, anterior olfactory nucleus, hippocampal formation, and amygdala. A few strongly immunoreactive neurons were consistently observed in the caudate putamen, and moderately or weakly labeled neurons were occasionally found in the nucleus accumbens. Within the brainstem, intensely labeled neurons were found in the trigeminal motor (V) and facial (VII) nuclei. Immunostained neurons were detected in the dorsal and the ventral horn of the spinal cord. These results reveal that the 5HT3R-immunoreactive neurons are broadly distributed throughout the rat brain and spinal cord, and suggest that this receptor can subserve significant participation in central nervous system neurotransmission.

Animals↗
PubMed1998

Transgenic expression of IFN-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration.

Type I IFNs, which include IFN-alpha, appear to have complex and broad-ranging actions in the central nervous system (CNS) that may result in protection or injury. To better understand these issues, we generated transgenic mice that produce IFN-alpha1 chronically from astrocytes. These glial fibrillary acidic protein-IFN-alpha transgenic mice developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, and neurodegeneration. Many features of this murine encephalopathy resembled those found in certain human encephalopathies of unknown etiology; these diseases, exemplified by Aicardi-Goutières syndrome and some viral encephalopathies, show increased intrathecal production of IFN-alpha. Our data suggest that IFN-alpha overproduction may be the primary factor initiating these human diseases. Following intracerebral infection with lymphocytic choriomeningitis virus, glial fibrillary acidic protein-IFN-alpha mice had significantly increased survival rates associated with markedly reduced virus titers and immune pathology in the brain but normal peripheral CTL responses. Therefore, the production of IFN-alpha in the CNS can be a two-edged sword that on the one hand confers protection against a lethal viral infection but on the other causes significant injury to the brain. These transgenic mice provide a novel animal model in which to further evaluate the mechanisms that underlie the diverse actions of type I IFNs in the intact CNS.

Animals↗
PubMed1998

Acute ethanol induces c-fos immunoreactivity in GABAergic neurons of the central nucleus of the amygdala.

The central nucleus of the amygdala (CNA) is a component of the brain reward pathway which is believed to represent an anatomical substrate for drugs of abuse. Previous studies have shown that acute ethanol administration induces the expression of c-fos in the CNA of rat brains. We report here, that over 70% of these c-fos immunoreactive neurons are GABAergic. This observation provides the first anatomical evidence that GABAergic neurons of the CNA are responsive to acute ethanol exposure and suggest that the GABAergic system of the CNA is a key neuronal substrate for ethanol actions on the central nervous system.

Amygdala↗
PubMed1998

The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

Amino Acid Sequence↗
PubMed1998

Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function.

The cytokines are a large and diverse family of polypeptide regulators with multiple regulatory functions that have been comprehensively evaluated in the immune system under strictly controlled experimental conditions. These peptide signals exhibit often unpredictable interactions when evaluated for their pathophysiological involvement in specific inflammatory conditions in vivo. In our joint efforts to understand the basis for early pathophysiological changes in the brains of HIV-infected subjects, we have developed animal models for lentivirus infections, and assessed the actions of various cytokines acutely on transmitter release properties in vitro, and in an in vivo transgenic mouse model. IL1beta, IL2, IL6, and IFNalpha will each enhance the release of AVP in slices of rat hypothalamus and amygdala. TGFbeta selectively blocks the ability of ACh to release AVP from hypothalamus or amygdala, but has no effects on the release stimulated by other cytokines. IFNalpha, but not TGFbeta will also activate CRH release; as with AVP, TGF selectively blocks the ACh-stimulated CRH release in both amygdala and hypothalamus. The IFNalpha-stimulated release of AVP and CRH appears to be mediated by cyclic GMP production, and this release by IFNalpha and IL-2 may be mediated in part by activation of constitutive nitric oxide synthase. These combined in vitro actions would suggest that cns cytokine actions should upregulate the hypothalamic pituitary adrenal axis. In a transgenic mouse model with increased astrocytic expression and release of the cytokine IL6, the HPA axis is upregulated, but the effect seems attributable to adrenocortical hypersensitization to ACTH. Lastly, in studies of cytokine mediated effects on astrocytic uptake of the excitatory transmitter glutamate, the reactive oxygen species hydrogen peroxide and peroxynitrite, but not nitric oxide, inhibited glutamate uptake in a concentration-dependent manner. Although superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes, the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium. Thus while reactive oxygen species do provide a potential path to neurotoxicity but one apparently not involving nitric oxide. These various data provide important opportunities for early therapeutic interventions in neuro-inflammatory states such as Neuro-AIDS.

Animals↗
PubMed1998

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Alcoholism↗
PubMed1998

Subcellular localization of tyrosine hydroxylase (TH) gene transcripts: new insights into the pattern of TH gene expression in the locus coeruleus under pharmacological stimulation.

To document the subcellular compartmentalization of the tyrosine hydroxylase (TH) primary (heterogeneous nuclear, hnRNA) and processed mRNA transcripts in vivo, we have studied the expression of the TH gene in the locus coeruleus of the rat brain in basal conditions and under pharmacological stimulation by reserpine. Using exon-specific probes and electron microscopic in situ hybridization in reserpine-treated animals, we have demonstrated that the TH mRNA is localized both in the perikaryal cytoplasm (in association with domains of the endoplasmic reticulum) and in the nucleus (in large and smaller aggregates). By comparing hybridization patterns with intron- and exon-specific probes, we have shown that the two main foci of nuclear TH RNA labeling correspond to the primary (hnRNA) transcript, while accessory secondary tracks or dots represent mature transcript devoid of introns. Finally, our data indicate that the pattern of expression of the TH gene is heterogeneous within the locus coeruleus neuron population. Under basal conditions, many neurons exhibit no detectable intron signal, although all locus coeruleus neurones express the TH gene. Other neurons display high intron labeling, and obviously express the gene at a much higher level. Upon reserpine stimulation, the number of neurons displaying detectable intron signals, as well as the intensity of the intron signal per neuron progressively increases during the first 24 h, suggesting that TH expressing neurons are progressively recruited for higher expression of this gene as the stimulation progresses.

Animals↗
PubMed1998

Magnetoencephalographic recordings demonstrate attentional modulation of mismatch-related neural activity in human auditory cortex.

It is widely agreed that the negative brain potential elicited at 150-200 ms by a deviant, less intense sound in a repetitive series can be modulated by attention. To investigate whether this modulation represents a genuine attention effect on the mismatch negativity (MMN) arising from auditory cortex or attention-related activity from another brain region, we recorded both the MMN and the mismatch magnetic field (MMF) elicited by such deviants in a dichotic listening task. Deviant tones in the attended ear elicited a sizable MMF that was well modeled as a dipolar source in auditory cortex. Both the MMN and MMF to unattended-ear deviants were highly attenuated. These findings support the view that the MMN/MMF elicited in auditory cortex by intensity deviants, and thus the underlying feature-analysis and mismatch-detection processes, are not strongly automatic but rather can be gated or suppressed if attention is strongly focused elsewhere.

Acoustic Stimulation↗