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M L Block

Publications and source records attributed to M L Block.

12 recordsLinked to original sources
PubMed2006

Potent regulation of microglia-derived oxidative stress and dopaminergic neuron survival: substance P vs. dynorphin.

Unregulated microglial activation has been implicated as a pivotal factor contributing to Parkinson's disease. Using mesencephalic neuron-glia cultures, we address the novel possibility that peptides endogenous to the substantia nigra (SN), substance P and dynorphin (10(-13)-10(-14) M), are opposing mediators of microglial activation and consequent DA neurotoxicity. Here, we identify that substance P (10(-13)-10(-14) M) is selectively toxic to DA neurons in a microglia-dependent manner. Mechanistically, substance P (10(-13)-10(-14) M) activated microglial NADPH oxidase to produce extracellular superoxide and intracellular reactive oxygen species (ROS). Neuron-glia cultures from mice lacking a functional NADPH oxidase complex (PHOX-/-) were insensitive to substance P (10(-13)-10(-14) M) -induced loss of DA neuron function. Mixed glia cultures from (PHOX-/-) mice failed to show a significant increase in intracellular ROS in response to substance P compared with control cultures (PHOX+/+). Further, dynorphin (10(-14) M) inhibited substance P (10(-13) M) -induced loss of [3H] DA uptake. Here we demonstrate a tightly regulated mechanism governing microglia-derived oxidative stress, where the neuropeptide balance of dynorphin and substance P is critical to DA neuron survival.

Animals↗
PubMed2004

Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.

The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX-/-) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX+/+). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult.

Animals↗
PubMed1996

Neonatal endotoxin exposure alters the development of social behavior and the hypothalamic-pituitary-adrenal axis in selectively bred mice.

Developmental differences in the biobehavioral consequences of immune activation in early life were investigated in two lines of mice selectively bred for high and low levels of inter-male aggressive behavior. At age 5 or 6 days, male mice were administered saline or 0.05 mg/kg gram-negative bacterial endotoxin (Escherichia coli, LPS, ip). There was a transient endotoxin-induced reduction in the growth rate of the neonates in the high-aggressive line. At age 45-50 days, the animals' behaviors were assessed in a dyadic task. Hypothalami and sera were harvested 20 min later. Rates of socially reactive behaviors to conspecific contact (i.e., kick, startle) were increased in the endotoxin-treated groups from both lines. For the high-aggressive line only, endotoxin treatment increased behavioral immobility, decreased attack frequency, and decreased levels of hypothalamic corticotrophin-releasing factor (CRF). The effects of endotoxin exposure in early life on socially reactive behaviors in later life were associated with endotoxin-induced individual differences in CRF levels in the high-aggressive line but not the low-aggressive line. The findings demonstrate long-term social developmental consequences of immune activation during the neonatal period.

Aggression↗
PubMed1994

Is the hypnotized subject lying?

Do the verbal reports of deeply hypnotized Ss truthfully reflect their subjective experiences of hypnotic suggestions? Experiment 1 established that the electrodermal skin conductance response (SCR) provides an effective method for detecting deception in the laboratory equally well in hypnotized and nonhypnotized Ss. In Experiment 2, deeply hypnotized and simulating Ss were administered a number of hypnotic suggestions in a typical hypnotic session, without mention of deception, and were questioned about their experiences while SCR measures were recorded concurrently. Results indicate that 89% of the hypnotized Ss' reports met the criterion for truthfulness, whereas only 35% of the simulators' reports met this criterion. Implications for the theory of hypnosis are discussed.

Adult↗
PubMed1991

Male saliva cues and female social choice in Mongolian gerbils.

Adult female Mongolian gerbils (Meriones unguiculatus) are preferentially attracted to saliva from adult nonsibling males when paired with saliva from male siblings. The focus of the present study was to evaluate the potential role of saliva in the formation of reproductive units. In Experiment 1, olfactory-directed investigations and mate choices of estrous females housed with their brothers and unrelated males were examined. Females sniffed unrelated males more frequently than siblings and were more interested in sniffing the mouth area than other body areas. Importantly, they also solicited and mated exclusively with unrelated males. The purpose of Experiment 2 was to ascertain the origin of the behaviorally active components of saliva by transecting the parotid salivary duct (PDT). When either sibling saliva or water was paired with saliva from a nonsibling PDT male, females did not show the typical preference for saliva from nonsiblings. When social preferences were examined in Experiment 3, virtually all females preferred intact nonsibling males to either PDT nonsibling males or siblings. Results from this study support the hypothesis that saliva is an important oral cue used by females in the selection of sociosexual partners. Furthermore, the parotid gland appears to be a significant source of salivary chemosignals.

Animals↗
PubMed1990

A voltage-dependent chloride current linked to the cell cycle in ascidian embryos.

A voltage-dependent chloride current has been found in early ascidian embryos that is a minor conductance in the oocyte and in interphase blastomeres but that increases transiently in amplitude by more than tenfold during each cell division. Repeated cycles in the density of this chloride current could be recorded for up to 6 hours (four cycles) in cleavage-arrested embryos, whether they were activated by sperm or calcium ionophore. These data suggest that there is a direct link between the cell cycle clock and the properties of this channel, a link that results in pronounced cyclical changes in the electrical properties of early blastomeres.

Animals↗
PubMed1988

Lineage-specific development of calcium currents during embryogenesis.

The development of electrophysiological properties of isolated, identified ascidian blastomeres was followed from the fertilized egg to the neurula, and the stage at which cells of different lineages first express different functional ion channel populations was determined. Little has been known about such events because of the difficulties of making voltage-clamp recordings from small embryonic cells and of identifying their developmental fates in dissociated preparations. The problem of small cell size was circumvented by using the whole-cell patch clamp, and identification was facilitated by the use of a species of ascidian, Boltenia villosa, in which endogenous pigment marks cells of specific developmental fates. Within approximately 3 hours after gastrulation, muscle-lineage blastomeres in these embryos developed a voltage-dependent calcium current while surrounding blastomeres of other lineages did not. At about the same time, all cells developed delayed outward potassium currents and lost the inwardly rectifying potassium currents present at earlier stages.

Animals↗
PubMed1987

Changes in sodium, calcium and potassium currents during early embryonic development of the ascidian Boltenia villosa.

1. The whole-cell variation of the patch clamp was used to study ion channel properties in the unfertilized oocyte, and in surgically isolated blastomeres from 2-, 4-, and 8-cell embryos of the ascidian, Boltenia villosa. 2. The unfertilized oocyte has three major voltage-dependent currents: a transient, inward Na+ current; a transient, inward Ca2+ current; and an inwardly rectifying K+ current. 3. The total surface area of the embryo, either measured by capacitance or calculated from cell diameters, increased about 2.5-fold between fertilization and the 8-cell stage. 4. The Na+ current almost completely disappeared from the embryo by the time of first cleavage and was undetectable in any of the blastomeres at the 8-cell stage. This loss was too large to be explained by the dilution of channels in the oocyte due to newly added membrane. 5. Both the Ca2+ current and the inwardly rectifying K+ current were maintained at constant or slightly increased density through the first three cleavage cycles. This suggests that these channels are added along with new membrane during these stages. 6. No differences in mean current densities of blastomeres of different developmental fates were detected through the 8-cell stage. 7. Continuous recordings in single egg cells between fertilization and first cleavage, using two-microelectrode voltage clamp, revealed the increase in capacitance, Ca2+ current amplitude, and K+ current amplitude, and the loss of Na+ current predicted from the blastomere studies.

Action Potentials↗
PubMed1981

Saliva as a chemical cue in the development of social behavior.

Throughout development, Mongolian gerbils engage in conspicuous naso-oral investigations of their social partners' mouth areas. The behavioral contribution of saliva-related stimuli in regulating oral-directed responses was studied during several important phases of the gerbil's social life. Weanlings were preferentially attracted to their mother's saliva, subadults at puberty preferred saliva of littermates to that of nonlittermates, and sexually experienced males preferred the saliva of estrous females to that of nonestrous females. The use of saliva as a discriminative cue during various developmental periods suggests that oral chemostimuli have a perennial role in regulating social interchanges.

Animals↗
PubMedDate not supplied

Cholinergic and dopaminergic blocking agents modulate water intake elicited by deprivation, hypovolemia, hypertomicity and isoproterenol.

In order to identify and differentiate separate components of an overall drinking system on neurochemical grounds, a few neuropharmacological blocking agents, already shown to affect the mediation of some thirst-related behaviors, were tested against a wide range of manipulations that elicit drinking behavior. Peripheral injections of scopolamine, an anticholinergic agent, or haloperidol, a catecholamine blocking agent with pronounced antidopaminergic actions, substantially reduced the water intake of rats induced to drink by periods of deprivations or by subcutaneous injections of either hypertonic saline, polyethylene glycol, or isoproterenol. When a combined injection of both scopolamine and haloperidol was given, hypovolemic and isoproterenol-induced drinking were about entirely eliminated but salt-aroused or deprivation-induced drinking were not totally abolished. In control studies, eating behavior elicited by either food deprivation or peripheral injection of 2-deoxy-d-glucose was not affected by these blocking agents. These experiments suggest that activation of cholinergic and dopaminergic neurons within central thirst-related systems are important physiological events underlying drinking behavior.

Animals↗