The role of lipid second messengers in aldosterone synthesis and secretion

Second messengers are small rapidly diffusing molecules or ions that relay signals between receptors and effector proteins to produce a physiological effect. Lipid messengers constitute one of the four major classes of second messengers. The hydrolysis of two main classes of lipids, glycerophospholipids and sphingolipids, generate parallel profiles of lipid second messengers: phosphatidic acid (PA), diacylglycerol (DAG), and lysophosphatidic acid versus ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate, respectively. In this review, we examine the mechanisms by which these lipid second messengers modulate aldosterone production at multiple levels. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis. Primary aldosteronism is a frequent endocrine cause of secondary hypertension. A thorough understanding of the signaling events regulating aldosterone biosynthesis may lead to the identification of novel therapeutic targets. The cumulative evidence in this literature emphasizes the critical roles of PA, DAG, and sphingolipid metabolites in aldosterone synthesis and secretion. However, it also highlights the gaps in our knowledge, such as the preference for phospholipase D-generated PA or DAG, as well as the need for further investigation to elucidate the precise mechanisms by which these lipid second messengers regulate optimal aldosterone production.     

Imaging emotional brain functions: Conceptual and methodological issues

This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor expression, action tendencies and monitoring/subjective feelings. Despite the advances in assessing the physiological correlates of emotional perception and learning processes, a critical appraisal shows that functional neuroimaging approaches encounter methodological difficulties regarding measurement precision (e.g., response scaling and reproducibility) and validity (e.g., response specificity, generalisation to other paradigms, subjects or settings). Since emotional processes are not only the result of localised but also of widely distributed activation, a more representative model of assessment is needed that systematically relates the hierarchy of high- and low-level emotion constructs with the corresponding patterns of activity and functional connectivity of the brain.     

Mechanisms of madness: evolutionary psychiatry without evolutionary psychology

Delusions are currently characterised as false beliefs produced by incorrect inference about external reality (DSM IV). This inferential conception has proved hard to link to explanations pitched at the level of neurobiology and neuroanatomy. This paper provides that link via a neurocomputational theory, based on evolutionary considerations, of the role of the prefrontal cortex in regulating offline cognition. When pathologically neuromodulated the prefrontal cortex produces hypersalient experiences which monopolise offline cognition. The result is characteristic psychotic experiences and patterns of thought. This bottom-up account uses neural network theory to integrate recent theories of the role of dopamine in delusion with the insights of inferential accounts. It also provides a general model for evolutionary psychiatry which avoids theoretical problems imported from evolutionary psychology.     

Molecular Characteristics and Peptide Specificity of Vasoactive Intestinal Peptide Receptors from Rat Cerebral Cortex

Vasoactive intestinal peptide (VIP) receptors have been identified in CNS by their chemical specificity and molecular size. Using synaptosomes isolated from rat cerebral cortex, it was shown that central VIP receptors discriminated among natural and synthetic VIP-related peptides, because half-maximal inhibition of [125I]VIP binding to synaptosomes was obtained for 0.6 nM VIP, 9 nM peptide histidine isoleucineamide (PHI), 50 nM VIP 2-28, 70 nM secretin, 100 nM rat growth hormone-releasing factor (GRF), and 350 nM human GRF. Other peptides of the VIP family, such as glucagon and gastric inhibitory polypeptide, did not interact with cortical VIP receptors. The molecular components of VIP receptors in rat cerebral cortex were identified after [125I]VIP cross-linking to synaptosomes using the cross-linker dithiobis(succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of synaptosomal proteins revealed two major [125I]VIP-protein complexes of Mr 49,000 and 18,000. The labeling of the Mr 49,000 component was specific, because it was abolished by native VIP, whereas the labeling of the Mr 18,000 component was not. Natural VIP agonists reduced the labeling of the Mr 49,000 component with the following order of potency: VIP greater than PHI greater than secretin approximately equal to rat GRF. In contrast, glucagon and octapeptide of cholecystokinin were without effect, a result indicating its peptide specificity. Densitometric scanning of autoradiographs showed that the labeling of the Mr 49,000 component was inhibited by low VIP concentrations between 10(-10) and 10(-6) M (IC50 = 0.8 nM), a result indicating the component's high affinity for VIP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated glutamate and NMDA disrupt production of the second messenger cyclic GMP in the early postnatal mouse cortex

The second messenger cyclic guanosine monophosphate (cGMP) plays many roles during nervous system development. Consequently, cGMP production shows complex patterns of regulation throughout early development. Elevated glutamate levels are known to increase cGMP levels in the mature nervous system. A number of clinical conditions including ischemia and perinatal asphyxia can result in elevated glutamate levels in the developing brain. To investigate the effects of elevated glutamate levels on cGMP in the developing cortex we exposed mouse brain slices to glutamate or N‐methyl D ‐aspartate (NMDA). We find that at early postnatal stages when the endogenous production of cGMP is high, glutamate or NMDA exposure results in a significant lowering of the overall production of cGMP in the cortex, unlike the situation in the mature brain. However, this response pattern is complex with regional and cell‐type specific exceptions to the overall lowered cGMP production. These data emphasize that the response of the developing brain to physiological disturbances can be different from that of the mature brain, and must be considered in the context of the developmental events occurring at the time of disturbance. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Parietal lobe variation in cercopithecid endocasts

In extant primates, the posterior parietal cortex is involved in visuospatial integration, attention, and eye‐hand coordination, which are crucial functions for foraging and feeding behaviors. Paleoneurology studies brain evolution through the analysis of endocasts, that is molds of the inner surface of the braincase. These may preserve imprints of cortical structures, such as sulci, which might be of interest for locating the boundaries of major cortical regions. Old World monkeys (Cercopithecidae) represent an interesting zoological group for evolutionary studies, because of their diverse ecologies and locomotor behaviors. In this study, we quantify parietal lobe variation within the cercopithecid family, in a sample of 30 endocasts including 11 genera and 17 species, by combining landmark‐based and landmark‐free geometric morphometric analyses. More specifically, we quantitatively assess variation of the parietal proportions based on landmarks placed on reliable anatomical references and of parietal lobe surface morphology through deformation‐based methods. The main feature associated with the cercopithecid endocranial variation regards the inverse proportions of parietal and occipital lobes, with colobines, Theropithecus, and Papio displaying relatively larger parietal lobes and smaller occipital lobes compared with cercopithecins. The parietal surface is anteroposteriorly longer and mediolaterally flatter in colobines, while longitudinally shorter but laterally bulging in baboons. Large parietal lobes in colobines and baboons are likely to be independent evolutionary traits, and not necessarily associated with analogous functions or morphogenetic mechanisms.     

Dopamine Gates Visual Signals in Monkey Prefrontal Cortex Neurons

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Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

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