A convulsant, 3-mercaptopropionic acid,decreases the level of GABA and GAD in rat pancreatic islets and brain

To investigate the properties of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamate decarboxylase (GAD), in the brain and the pancreatic islets of the rat, GABA concentration in the brain and the pancreatic islets was measured after intraperitoneal administration of 3-mercaptopropionic acid (3-MP) at 25 mg/kg. 60 min after the administration of 3-MP, GABA concentration in the hypothalamus, the superior colliculus and the hippocampus of the brain decreased by 20–30% and in the pancreatic islets by 35%. The concentration in the pancreatic acini did not change. Western blotting showed that GAD activity in the pancreatic islets decreased after administration of 3-MP compared to the control. The activity of GAD in the pancreatic islets as well as brain can be modified by a convulsant, in this case 3-MP. These results suggest the properties of GAD may be similar in the pancreatic islets and brain.     

Cholinomimetics produce seizures and brain damage in rats

Microinjections of the cholinergic agonists, carbachol and bethanechol, either into the amygdala or into the dorsal hippocampus produced sustained limbic seizures and brain damage in rats. Systemic administration of pilocarpine in rats resulted in a sequence of convulsive disorders and widespread brain damage as well. Scopolamine prevented the development of convulsive activity and brain damage produced by cholinomimetics. These results suggest that the excessive stimulation of cholinergic muscarinic receptors can lead to limbic seizures and brain damage. It is postulated that muscarinic cholinergic mechanisms are linked to the etiology of temporal lobe epilepsy and epileptic brain damage.     

Purification and properties of ornithine aminotransferase from rat brain

Ornithine aminotransferase (E.C. 2.6.1.13) from rat brain was purified 100-fold by ammonium sulphate fractionation, DEAE cellulose chromatography, calcium phosphate gel and alumina C gamma gel. Pyridoxal phosphate was essential for maximum activity of the enzyme. The brain enzyme did not differ from liver and kidney enzymes in properties such as pH optimum, Km, substrate specificity and the inhibition by branched chain amino acids. Unlike rat liver enzyme, brain ornithine aminotransferase was able to catalyze the reaction between L-lysine and 2-oxoglutarate. Spermidine and spermine inhibited brain ornithine aminotransferase activity.     

Comparison of dihydrodiazepam enantiomers: Metabolism,serum binding and brain receptor binding

Summary Dihydrodiazepam is a diazepam prodrug, as shown by its in vitro metabolism by rat and mouse liver and brain microsomal fractions, and its displacing activity on brain diazepam binding. The mechanism of bioactivation is discussed. Stereoselectivity of metabolism and of binding to specific benzodiazepine binding sites in brain synpatosomes and serum albumin were studied.Acknowledgment. The authors are grateful to Dr. J. Wolford for the synthesis of³H-diazepam.     

Physical growth and brain development of captive-bred male and female squirrel monkeys, Saimiri sciureus.

The physical growth and brain development of the captive bred male and female squirrel monkeys have shown that the male grows at a significantly faster rate with respect to these parameters in the postnatal life, starting from preweaning stage as compared to the female infant. During the prenatal life the male and the female fetuses grow at similar rates and show comparable brain development as indicated by its weight.     

Platelet monoamine oxidase B: use and misuse

The human platelet in addition to having serotonin (5-HT) receptors, uptake carriers (receptor) and transmitter storage vesicles, primarily possesses mitochondrial monoamine oxidase (MAO) type B. Similar to the major form of MAO in the human brain, this enzyme actively oxidizes A-B and B substrates (tyramine, dopamine, phenylethylamine) as well as the novel secondary amine anticonvulsant, milacemide and dopaminergic neurotoxin, MPTP. 5-HT oxidation is hardly affected by the platelet enzyme and MAO inhibitors have no net effect on its accumulation. MAO-B is selectively inhibited by 1-deprenyl and thus the platelet enzyme may be useful to monitor the anti-Parkinson activity of such drugs, as related to their ability to inhibit brain MAO-B. The oxidation of the anticonvulsant, milacemide, to glycine in vitro and in vivo by MAO-B, may herald new prospects for the development of inert prodrugs capable of being metabolized to neuroactive substances by MAO-B. The plasma levels of their metabolites may be an index of MAO-B activity found in the platelet and brain.     

Platelet monoamine oxidase B: Use and misuse

The human platelet in addition to having serotonin (5-HT) receptors, uptake carriers (receptor) and transmitter storage vesicles, primarily possesses mitochondrial monoamine oxidase (MAO) type B. Similar to the major form of MAO in the human brain, this enzyme actively oxidizes A-B and B substrates (tyramine, dopamine, phenylethylamine) as well as the novel secondary amine anticonvulsant, milacemide and dopaminergic neurotoxin, MPTP. 5-HT oxidation is hardly affected by the platelet enzyme and MAO inhibitors have no net effect on its accumulation. MAO-B is selectively inhibited by 1-deprenyl and thus the platelet enzyme may be useful to monitor the anti-Parkinson activity of such drugs, as related to their ability to inhibit brain MAO-B. The oxidation of the anticonvulsant, milacemide, to glycine in vitro and in vivo by MAO-B, may herald new prospects for the development of inert prodrugs capable of being metabolized to neuroactive substances by MAO-B. The plasma levels of their metabolites may be an index of MAO-B activity found in the platelet and brain.     

Aldose metabolism in developing human fetal brain and liver

Summary Aldose reductase, sorbitol dehydrogenase, and glucose-6-phosphate dehydrogenase enzyme activities were studied in human foetal brain and liver at different periods of gestation. Aldose reductase activity in liver disappears after 16 weeks of gestation whereas sorbitol dehydrogenase keeps on increasing in liver as well as in brain. In utero, some glucose metabolism may be mediated through an active sorbitol pathway in human fetuses.Acknowledgments. These studies were supported by the Indian Council of Medical Research.     

Physical growth and brain development of captive-bred male and female squirrel monkeys,Saimiri sciureus

Summary The physical growth and brain development of the captive bred male and female squirrel monkeys have shown that the male grows at a significantly faster rate with respect to these parameters in the postnatal life, starting from preweaning stage as compared to the female infant. During the prenatal life the male and the female fetuses grow at similar rates and show comparable brain development as indicated by its weight.Acknowledgments. This work was supported by USPHS Grants RR-00165 and HD-06087 from National Institutes of Health. The technical assistance of Mrs Judie Wells is greatly appreciated.     

Isoquinolines,beta-carbolines and alcohol drinking: Involvement of opioid and dopaminergic mechanisms

Summary Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several dinstinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagoists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.     

Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms

Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several distinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagonists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.     

Neuroimaging, nutrition, and iron-related genes

Several dietary factors and their genetic modifiers play a role in neurological disease and affect the human brain. The structural and functional integrity of the living brain can be assessed using neuroimaging, enabling large-scale epidemiological studies to identify factors that help or harm the brain. Iron is one nutritional factor that comes entirely from our diet, and its storage and transport in the body are under strong genetic control. In this review, we discuss how neuroimaging can help to identify associations between brain integrity, genetic variations, and dietary factors such as iron. We also review iron’s essential role in cognition, and we note some challenges and confounds involved in interpreting links between diet and brain health. Finally, we outline some recent discoveries regarding the genetics of iron and its effects on the brain, suggesting the promise of neuroimaging in revealing how dietary factors affect the brain.     

Monoamine oxidase activity of the brain of Locusta migratoria in normal conditions and after intoxication by two insecticides: chlordimeform and dieldrin]

Our investigations have shown up an MAO activity in locust brain, by the use of a radio-isotopic method, as much at larval as at adult stage. This MAO activity is in a sample of 34,3 dpm/mg of brain tissue (wet weight). Investigations have also been undertaken on effects of dieldrin and chlordimeform poisoning on this MAO activity. Even at sublethal dosages, chlordimeform causes a significant inhibition of MAO activity in vivo. This finding is in accordance with Beeman and Matsumura's work in vitro. Moreover, acute poisoning by dieldrin produces more than 60% of inhibition of MAO, 3 hours after administration of 115 microng of this insecticide by injection in the hoemocelian cavity.     

The dopamine D4 receptor: biochemical and signalling properties

Dopamine is an important neurotransmitter that regulates several key functions in the brain, such as motor output, motivation and reward, learning and memory, and endocrine regulation. Dopamine does not mediate fast synaptic transmission, but rather modulates it by triggering slow-acting effects through the activation of dopamine receptors, which belong to the G-protein-coupled receptor superfamily. Besides activating different effectors through G-protein coupling, dopamine receptors also signal through interaction with a variety of proteins, collectively termed dopamine receptor-interacting proteins. We focus on the dopamine D4 receptor, which contains an important polymorphism in its third intracellular loop. This polymorphism has been the subject of numerous studies investigating links with several brain disorders, such as attention-deficit hyperactivity disorder and schizophrenia. We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.     

Correlations between the neurobiology of colour vision and the psycholinguistics of colour naming.

Neurobiological experiments demonstrate that colour sensation is perceived by the brain by processes which, in principle, follow the opponent colour pairs scheme proposed by Hering in 1874. Tests on colour naming in various European, Asian and Central American languages have shown that the opponent scheme is also reflected in psycholinguistics. The linguistic evolution of colour terms proposed by Berlin and Kay (1969) is correlated directly with the ontogenetic development of language in children as elucidated by Jakobson (1941). Colour vision is therefore a suitable field for interdisciplinary investigations of brain processes and linguistics.     

Increased contents of phenylethanolamine, m-octopamine and p-octopamine in the hypothalamus and brain stem of spontanously hypertensive rats (S.H.R. Kyoto)]

Phenylethanolamine, p-octopamine and m-octopamine contents were determined in the hypothalamus and the brain stem of spontaneously hypertensive Rats (S.H.R. Kyto) and the corresponding controls (Wistar Kyoto). In three-week-old Rats, phenylethanolamine and p-octopamine are found to be present in S.H.R. hypothalamus and brain stem at concentrations twice as high as compared to Wistar Kyoto Rats. The amount of m-octopamine is 5-fold higher in the brain stem of S.H.R. Rats as compared to Wistar Kyoto Rats.     

The comparative biology of neuromelanin and lipofuscin in the human brain

Neuromelanin and lipofuscin are two pigments produced within the human brain that, until recently, were considered inert cellular waste products of little interest to neuroscience. Recent research has increased our understanding of the nature and interactions of these pigments with their cellular environment and suggests that these pigments may, indeed, influence cellular function. The physical appearance and distribution of the pigments within the human brain differ, but both accumulate in the aging brain and the pigments share some structural features. Lipofuscin accumulation has been implicated in postmitotic cell aging, while neuromelanin is suggested to function as an iron-regulatory molecule with possible protective functions within the cells which produce this pigment. This review presents comparative aspects of the biology of neuromelanin and lipofuscin, as well as a discussion of their hypothesized functions in brain and their possible roles in aging and neurodegenerative disease.     

Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response.     

Developmental and pathological angiogenesis in the central nervous system

Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases.