Biomedical subjects

J E Sherin

Publications and source records attributed to J E Sherin.

6 recordsLinked to original sources

PubMed1998

Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat.

The tuberomammillary nucleus (TMN) is the major source of histaminergic innervation of the mammalian brain and is thought to play a major role in regulating wake-sleep states. We recently found that sleep-active neurons in the ventrolateral preoptic nucleus (VLPO) provide a major input to the TMN, but the specificity of this projection and the neurotransmitters involved remain unknown. In this study, we examined the relationship of VLPO efferents to the TMN using both retrograde and anterograde tracing, combined with immunocytochemistry. We found that the descending projection from the VLPO selectively targets the cell bodies and proximal dendrites of the histaminergic TMN. In addition, VLPO axons could be traced into the brainstem, where they provided terminals in the the serotoninergic dorsal and median raphe nuclei, and the core of the noradrenergic locus coeruleus. Approximately 80% of the VLPO neurons that were retrogradely labeled by tracer injections including the TMN were immunoreactive either for galanin or for glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA. Virtually all of the galaninergic neurons in the VLPO were also GAD positive. Our results indicate that the VLPO may provide inhibitory GABAergic and galaninergic inputs to the cell bodies and proximal dendrites of the TMN and other components of the ascending monoaminergic arousal system. Because these cell groups are simultaneously inhibited during sleep, the VLPO sleep-active neurons may play a key role in silencing the ascending monoaminergic arousal system during sleep.

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PubMed1997

Effects of sleep on wake-induced c-fos expression.

We investigated the effects of sleep on wake-induced c-fos expression in the cerebral cortex of rats and c-fos-lacZ transgenic mice. In the cortex of rats, the levels of c-Fos, detected both by immunocytochemistry and Western blot, remained high during 6 or 12 hr of enforced wakefulness but declined rapidly (within 1 hr) with increasing time of recovery sleep. Similarly, in the transgenic mice in which lacZ expression is driven from the c-fos promoter, beta-galactosidase activity was high after enforced wakefulness and declined with increasing amounts of sleep. These results suggest that the decrease in c-Fos protein in cortical neurons during sleep may be attributable to cessation of c-fos expression, activation of a process that degrades the wake-induced c-Fos, or both.

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PubMed1997

Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages.

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy).

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PubMed1996

Activation of ventrolateral preoptic neurons during sleep.

The rostral hypothalamus and adjacent basal forebrain participate in the generation of sleep, but the neuronal circuitry involved in this process remains poorly characterized. Immunocytochemistry was used to identify the FOS protein, an immediate-early gene product, in a group of ventrolateral preoptic neurons that is specifically activated during sleep. The retrograde tracer cholera toxin B, in combination with FOS immunocytochemistry, was used to show that sleep-activated ventrolateral preoptic neurons innervate the tuberomammillary nucleus, a posterior hypothalamic cell group thought to participate in the modulation of arousal. This monosynaptic pathway in the hypothalamus may play a key role in determining sleep-wake states.

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PubMed1993

Oligodendrocyte proteoglycans: modulation by cell-substratum adhesion.

The signals that trigger the cytodifferentiation of oligodendrocytes (OLGs) are largely unknown. Using as a model system cultures of pure OLGs, we have shown that adhesion to a substratum initiates myelinogenesis (Yim SH, Szuchet S, Polak PE, J Biol Chem 261:11808-11815, 1986). It was of interest to investigate whether components such as proteoglycans (PGs) play any role in the biology of OLGs as it pertains to myelinogenesis. We set out to determine first, whether OLGs carry PGs; second, the nature of the association of these components with OLG plasma membrane; and third, if and how these PGs are modulated by OLG-substratum interaction. We compared the expression and characteristics of PGs extracted with different solvents from nonattached (B3.f) and attached (B3.fA) OLGs. B3.f and B3.fA OLG cultures were labeled with carrier-free 35SO4(2-) in serum-free medium. After removing excess label, OLGs were treated with heparin to extract susceptible components. Pellets were then exposed to 1% Triton X-100 plus 0.1 M NaCl and subsequently to 4 M guanidine-HCl plus 0.5 M NaCl. Solutions containing extracted material were characterized by size-exclusion chromatography, SDS-PAGE, and enzymatic degradation. Herein we report that (1) OLGs display [35S]PGs on their surface within 24 hr of substratum adhesion, and (2) these PGs can be operationally classified as peripheral and integral. We further show that the peripheral PGs are of high and intermediate size as assessed by size-exclusion chromatography and are segregated within the plasma membrane in such a way that the species with intermediate mass are extracted while OLGs remain adhered, whereas the high-molecular-weight species are only extracted after OLGs have been detached. Heparin also dislodges a number of sulfated proteins/Gps. Only a single class--high molecular weight--of integral PGs was identified; this PG requires guanidine-HCl for extraction. All PGs belong to the heparan sulfate class as evidenced by their degradation with heparitinase and their lack of susceptibility to chondroitinase ABC. The common theme of our findings is that these macromolecules have basal levels of expression in the nonadhered OLGs but undergo an adhesion-induced enhancement in their syntheses. We postulate that these PGs (1) play a role in OLG-substratum adhesion and hence myelinogenesis, and (2) may be determinants in establishing OLG polarity. Such polarization is the first overt sign of OLG functional differentiation and occurs prior to any morphological differentiation, e.g., extension of processes does not occur until 48 hr later when the plasma membrane is already polarized.

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PubMed1990

N-methyl-D-aspartate-evoked calcium uptake by kitten visual cortex maintained in vitro.

As a functional measure of NMDA receptor effectiveness in kitten striate cortex, the uptake of 45Ca by visual cortical slices was measured after 2 minute bath applications of N-methyl-D-aspartate (NMDA). Significant Ca uptake occurred in response to 12.5-100 microM NMDA in slices prepared from visual cortex of normal animals aged 28-48 days. Basal uptake (in the absence of NMDA) was increased and evoked uptake was decreased in visual cortical slices prepared from age-matched dark-reared animals. Four days of binocular deprivation in otherwise normally reared animals had no effect on basal uptake, but significantly lowered NMDA-evoked Ca uptake at agonist concentrations greater than 25 microM. These data suggest that even brief manipulations of sensory experience are sufficient to alter visual cortical calcium regulation.

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