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Biomedical subjects

G R Elliott

Publications and source records attributed to G R Elliott.

At least 91 records · Page 5Linked to original sources
PubMed1978

S-adenosylmethionine-dependent N-methyltransferase activity in autopsied brain parts of chronic schizophrenics and controls.

The transmethylation hypothesis of schizophrenia proposes that the disease results from excessive accumulation of methylated derivatives of biogenic amines. To test the hypothesis that an abnormality in S-adenosylmethionine-dependent N-methyltransferase (SAM enzyme) might play a role in schizophrenia, the authors compared SAM enzyme activity of in vitro preparations of 6 brain regions obtained at autopsy from chronic schizophrenics and nonschizophrenic controls. An analysis of variance demonstrated statistically significant differences among brain regions but not between schizophrenics and controls.

Amygdala↗
PubMed1978

N5,10-methylenetetrahydrofolate reductase activity in autopsied brain parts of chronic schizophrenics and controls and in vitro tryptoline formation.

We and others have shown that in vitro tryptoline (tetrahydro-beta-carboline) formation accounts for the apparent-N-methylating activity of a brain enzymatic preparation using 5-methyltetrahydrofolic acid (5-MTHF) as a cofactor and tryptamines or catecholamines as substrates. This paper demonstrates that N5,10-methylenetetrahydrofolate reductase (methylene reductase) is responsible for this in vitro tryptoline formation with human brain enzymatic preparations. Others have described a folate-responsive psychosis which was associated with markedly reduced methylene reductase activity. Therefore, we also have examined this enzymatic activity in autopsied brains from chronic schizophrenics and controls. There were no statistically significant differences between activities for schizophrenics and controls in the six brain regions studied. Thus, although it is possible that some subgroup of schizophrenics may be characterized by abnormal methylene reductase activity, there does not appear to be a general association between the two.

Animals↗
PubMed1977

Stereotypy and hyperactivity in rats receiving ethanol and a monoamine oxidase inhibitor.

The combined administration of tranylcypromine (TCP) and ethanol to rats produced both a marked increase in general locomotion such as walking and running and the appearance of repetitive stereotyped head and trunk weaving, forepaw padding, and circling movements. Pretreatment with p-chlorophenylalanine (pCPA) abolished the stereotyped behaviors. In contrast, animals pretreated with alpha-methyl-p-tyrosine (AMPT) were virtually indistinguishable from those receiving only TCP + ethanol, except for a decrease in running behaviors. The above results are consistent with a serotonergic mediation of these specific stereotypes. The mechanisms by which TCP + ethanol might produce these effects are discussed.

Animals↗
PubMed1977

Platelet methylene reductase activity in schizophrenia.

A case of a folate-responsive psychosis that was associated with a defect in N5-10-methylenetetrahydrofolate reductase (methylene reductase) suggested the need to examine whether abnormally low activity of this enzyme might be of etiological importance in schizophrenia. We now report that there were no statistically significant differences in the platelet methylene reductase activity of chronic schizophrenics, compared with either hospitalized or nonhospitalized age-matched control subjects. Although it is possible that a larger survey might reveal a subpopulation of schizophrenics who are characterized by abnormal methylene reductase activity, this study suggests that chronic schizophrenia is not generally associated with such changes.

Adult↗
PubMed1977

A genetic analysis of aggressive behavior in two strains of mice.

Examination of BALB/cJ and A/J mouse strains revealed marked differences in their levels of isolation-induced aggression. Using the dangler paradigm, we found that BALB/cJ males were uniformly aggressive, while A/J males showed no tendency to attack. Genetic analysis showed that the expression of aggressive behavior in the F1, F2, and backcross generations was consistent with the transmission of high aggressivity as a single, autosomal recessive trait. Although the data are consistent with a major-locus effect, more complex polygenic modes of inheritance have not been excluded.

Aggression↗
PubMed1976

The tryptolines: effect of intraventricular administration on spontaneous motor activity of rats.

The pharmacologic properties of the tryptolines, hindered analogues of the tryptamines, were studied behaviorally in rats. Following intraventricular injections, it was found that spontaneous motor activity decreased markedly during the initial 25 mins when compared with saline. Since both the tryptolines and tryptamines have been shown to be inhibitors of 5-hydroxytryptamine uptake, it may be possible that these compounds are acting indirectly throught an effect on the serotonergic system.

Animals↗
PubMed1976

Tryptoline inhibition of serotonin uptake in rat forebrain homogenates.

We have examined the effects of six tryptolines (tetrahydro-beta-carbolines) upon 5-hydroxytryptamine (5-HT) uptake into rat forebrain homogenates. All six were found to be competitive inhibitors of 5-HT uptake. 5-Hydroxytryptoline, the most potent inhibitor, had an inhibitor constant (Ki) of 0.3 mugM. Both 5-hydroxytryptoline and 5-hydroxymethtryptoline were also shown to be relatively selective against 5-HT uptake, being 20 times less potent against norepinephrine uptake and 40 times less potent against dopamine. Since it is possible that tryptolines might be formed as a result of alcohol consumption, these results suggest that it is important to examine the possibilities that such compounds mediate some of the effects of alcohol upon serotonergic pathways.

Alcohol Drinking↗
PubMed1975

Neuroregulators and sleep mechanisms.

Information which has emerged thus far relates to the overall transmitter mechanisms of sleep. The data, while conflicting, point to the involvement of many neuroregulators at numerous integrative levels of the process. However the long term question still remain: what triggers and maintain sleep, what stops sleep, what occurs to the body and brain during sleep--in essence, why sleep? These questions are now problems for behavioral neurochemists, whereas in a previous era, they were problems for philosophers. Unfortunately, our answers to date, while in another idiom, have hardly been more complete or satisfying. To answer these questions, it will be necessary to understand, in detail, the manner in which neurobiochemical processes relate to the functional physiology of sleep. Although existing studies have given invaluable insight into the neurochemical anatomy of sleep, we have only recently acquired the technical and biochemical expertise necessary to investigate sleep as it occurs normally. Future research must focus on the dynamic changes associated with the regulatory mechanisms of neurotransmitters. Many questions can be asked. With sleep transitions, what changes occur in transmitter content, synthesis, or release? Are there changes in metabolic pathways, reflecting a shift from intra- to interneuronal metabolism? What changes occur in pre- and postsynaptic neurotransmitter receptors to affect sensitivity? What constraints do genetic (245) and environmental (246) factors impose upon these mechanisms? Knowledge of such parameters will allow us to construct more complete models of the neuroregulatory basis of sleep and waking. However, as we acquire this knowledge, we must avoid the temptation of assuming causation when the evidence merely shows correlation. Neuroregulation are involved in the control of number different behaviors; and, at present, we have few, if any, methods of establishing causative links between a specific neuroregulator and a specific behavioral state. Yet, even without an understanding of what "causes" sleep, we may be able to develop pharmacological agents which permits discrete alteration of sleep mechanisms in a more physiological and specific manner. This potential for manipulation of sleep is of obvious importance in illnesses such as insomnia, narcolepsy, and sleep apnea (247, 248). In addition, it may be valuable in the treatment of such conditions as psychosis and depression, where sleep disturbances are an important component of the illness. For example, delirium tremens might be best understood as a psychotic episode which is the result of an aspect of sleep emerging into wakefulness. The range and breadth of both the basic questions and the potential application of sleep research portend an exciting future for this field.

Acetylcholine↗
PubMed1975

Genetic determination of aggressive behavior and brain cyclic AMP.

Inbred mouse strains exhibit differences in brain cyclic AMP concentrations. In two mouse strains, we have shown that both the tendency for aggressive attack and high brain cyclic AMP content are inherited as recessive traits and that these traits maintain a close association in segregating generations.

Aggression↗