LORETA Neurofeedback in the Precuneus: Operant Conditioning in Basic Mechanisms of Self-Regulation.

Low-resolution brain electomagnetic tomography (LORETA) neurofeedback provides a mechanism to influence the electrical activity of the brain in intracranial space. The aim of this study was to determine the effects of LORETA neurofeedback (LNFB) in the precuneus as a mechanism for improving self-regulation in controls and a heterogeneous diagnostic group (DX). Thirteen participants completed between 10 and 20 sessions of LNFB training in a 3-voxel cluster in the left precuneus. The participants included 5 nonclinical university students, and 8 adults with heterogeneous psychiatric diagnoses. We assessed the effects of LNFB with neurophysiological measures as well as pre- and post-Personality Assessment Inventory (PAI) subscales and selected subtests from the Delis-Kaplan Executive Function System (DKEFS). There was a significant total relative power increase at the precuneus for baseline contrasts for the control group. The DX group did not reach significant levels. All participants showed improvements in executive functions and tended to report significantly less psychopathology. The basic neural mechanisms of self-regulation are poorly understood. The data obtained in this study demonstrate that LNFB in a heterogeneous population enhances executive functions while concordantly decreasing endorsement of psychological symptoms. The alpha frequency in the brain may represent integrative functioning relative to operant efficiency and self-regulatory mechanisms.

Dexamethasone and stress upregulate Kv1.5 K+ channel gene expression in rat ventricular myocytes.

Hormones may produce long-term effects on excitability by regulating K+ channel gene expression. Previous studies demonstrated that administration of dexamethasone, a glucocorticoid receptor agonist, to adrenalectomized rats, rapidly induces Kv1.5 K+ channel expression in the ventricle of the hear. Here, RNase protection assays and Northern blots are used to examine the cell type specificity of dexamethasone action and to test whether Kv1.5 gene expression can be regulated by a physiological stimulus. We show that Kv1.5 mRNA expression in the central nervous system is highest in the hypothalamus. However, dexamethasone treatment of adrenalectomized rats fails to affect Kv1.5 mRNA levels in hypothalamus or lung. In contrast, dramatic upregulation of Kv1.5 mRNA is seen in skeletal muscle and pituitary. Increased Kv1.5 message also found in isolated ventricular cardiomyocytes following in vivo treatment with dexamethasone. Finally, it is shown that cold stress of intact rats significantly increases cardiac Kv1.5 mRNA expression. We conclude that dexamethasone induction of Kv1.5 gene is tissue-specific. Furthermore, our results suggest that stress may act via glucocorticoids to increase Kv1.5 gene expression in ventricular cardiomyocytes. Hence, K+ channel gene expression can be influenced by physiological and pharmacological stimuli.

Induction of glucocorticoid receptor expression in hypothalamic magnocellular vasopressin neurons during chronic hypoosmolality.

The site of action for the modulation of hypothalamo-neurohypophyseal function by adrenal steroids is not known. Glucocorticoid receptors (GR) are an obvious potential site of action, but there have been conflicting reports of GR localization in magnocellular neurons. We confirm studies finding undetectable levels of GR in vasopressin or oxytocin neurons, but now report that chronic hypoosmolality induces the expression of GR in magnocellular vasopressin neurons, but not oxytocin neurons. These data support the hypothesis that the vasopressin gene can be directly inhibited by glucocorticoids, and that the induction of GR expression in magnocellular neurons may be part of a redundant set of mechanisms to suppress the expression of AVP during periods of prolonged hypoosmolality. This mechanism represents a novel form of steroid feedback control in brain.

In situ hybridization analysis of arginine vasopressin gene transcription using intron-specific probes.

In situ hybridization histochemistry with a probe directed against an intron sequence of the rat arginine vasopressin (AVP) gene was used to demonstrate localization and regulation of AVP heteronuclear RNA in discrete brain regions. Hybridization with an AVP intron I (AVPinI) probe revealed specific hybridization confined to cell nuclei of paraventricular nucleus, supraoptic nucleus (SON), and suprachiasmatic nucleus neurons of the rat hypothalamus. Grain counts revealed that the signal generated by the AVPinI probe represented 1.9% of that derived from an AVP exon C probe (AVPexC) in the SON. Interestingly, in the suprachiasmatic nucleus the proportion of AVPinI to AVP exon C ratio was much higher (12%), suggesting either increased transcription of the AVP gene or changes in posttranscriptional RNA processing. Regulatory experiments revealed that 2.6-fold increases in AVPinI signal could be visualized in the SON as little as 30 min after an acute salt load, a period during which no significant change in cytoplasmic AVP mRNA could be observed. In response to chronic salt loading, both AVP heteronuclear RNA and AVP mRNA were up-regulated. These data compared favorably with transcription rate values determined by nuclear run-on assay, suggesting that intronic in situ hybridization affords a relatively reliable method for assessment of rapid changes in gene transcription in individual central nervous system neurons.

Molecular cloning of a mineralocorticoid (type I) receptor complementary DNA from rat hippocampus.

Rat brain expresses two types of corticosteroid-binding proteins. The type I receptor binds corticosterone with high affinity and is structurally related to the kidney mineralocorticoid receptor (MR), while the type II or classical glucocorticoid receptor binds corticosterone with lower affinity and displays an in vivo preference for dexamethasone. Here we describe the isolation and characterization of a cDNA coding for the MR, from a rat hippocampus cDNA library, by low stringency hybridization to radiolabeled human glucocorticoid receptor cDNA. The nucleotide and deduced amino acid sequence for rat hippocampal MR displays extensive homology to a MR cDNA isolated from human kidney, suggesting that they are orthologous genes. Southern analysis suggests that there is only one gene for the MR, and in vitro expression of the receptor generates a high affinity corticosterone-binding protein. These data provide evidence to support the contention that a single gene gives rise to the MR in renal tissues and type I receptors in the brain.

Hypothalamic dynorphin and vasopressin mRNA expression in normal and Brattleboro rats.

Peptides derived from prodynorphin and provasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons of the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated with physiological manipulations that elevate plasma levels of vasopressin (VP), such as dehydration and salt-loading. Evidence indicates that both VP- and prodynorphin-derived peptides are secreted under such conditions. With chronic osmotic challenge, the mRNAs for both prodynorphin and provasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, and not within nonmagnocellular cell groups projecting elsewhere in the brain. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain. These results from microdissected tissues have been coupled with the more anatomically precise method of in situ hybridization histochemistry. Using 35S-radiolabeled synthetic oligonucleotides complementary to VP and dynorphin mRNAs, these mRNAs have been autoradiographically localized to magnocellular parikarya in the rat hypothalamus. Results also indicate that this technology can be used for regulatory studies, as evidenced by the increased hybridization of VP oligonucleotide to hypothalamic nuclei from salt-loaded rats.

Vasopressin mRNA regulation in individual hypothalamic nuclei: a northern and in situ hybridization analysis.

The present study examines the relative levels of vasopressin (AVP) mRNA within the paraventricular (PVN), supraoptic (SON), and suprachiasmatic (SCN) nuclei of the rat hypothalamus, and details the rates at which these levels change over the course of a 6 d salt-loading regimen. The quantitation of vasopressin mRNA was achieved by using three different procedures: (1) cell-free translation in rabbit reticulocyte lysate or (2) Northern analysis of poly(A)RNAs isolated from micro-punch dissected SON, PVN, and SCN, and (3) in situ hybridization histochemistry. The former involved the quantitative immunoprecipitation of the neurophysin precursors containing arginine8-vasopressin (AVP) or oxytocin, and the latter two techniques employed a radiolabeled synthetic oligodeoxynucleotide complementary to the 3' region of the AVP mRNA. Both the cell-free studies and the Northern gel analyses detected a sevenfold increase of AVP mRNA in the SON, a fivefold increase in the PVN, and no significant change in the SCN following 6 d of salt-loading. After the initiation of salt-drinking, these increases were shown to occur between 24 and 48 hr in the SON and between 48 and 72 hr in the PVN. The in situ hybridization studies revealed the anatomically correct hybridization of either 32P- or 3H-labeled AVP oligonucleotide to magnocellular perikarya within both the SON and PVN. Autoradiographic grains could be shown to be confined to the cytoplasm of these cells, and could be co-localized with immunoreactivity directed against the carboxy terminus of the AVP percursor. Comparison of x-ray level autoradiograms of control and 6 day salt-loaded SON revealed up to a sevenfold increase in specific signal in the salt-loaded sections. It is concluded that the response of AVP mRNA to osmotic stimuli in the three hypothalamic nuclei is heterogeneous, and that this heterogeneity can be explained by separating AVP neurons into two systems: one responsible for eliciting the antidiuretic actions of AVP via plasma AVP levels, and the other involved in CNS activities not directly involved with antidiuresis.

Coordinate expression of hypothalamic pro-dynorphin and pro-vasopressin mRNAs with osmotic stimulation.

Peptides derived from pro-dynorphin and pro-vasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons in the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated using physiological manipulations known to increase plasma vasopressin levels, such as dehydration and salt-loading. With chronic osmotic challenge, the mRNAs for both pro-dynorphin and pro-vasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, but not within the nonmagnocellular suprachiasmatic nucleus cell groups projecting elsewhere than the neural lobe. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain.

A comparative study of the effects of insulin/glucagon infusions, parenteral amino acids and high dose corticosteroids on survival in a rabbit model of acute fulminant hepatitis.

Acute fulminant hepatitis was induced in 55 healthy adult male rabbits with the potent hepatotoxin galactosamine hydrochloride (3.75 mmoles per kg i.v.). Control rabbits (n = 27) were divided into three groups: Group I (n = 10) underwent sham surgery for placement of an indwelling central venous catheter; Group II (n = 9) received 5% dextrose and water via an indwelling central venous catheter, and Group III (n = 8) received daily intramuscular injections of 0.9% sodium chloride. Treated rabbits (n = 28) also consisted of three groups: Group IV (n = 9) received 12-hr intravenous infusions of insulin (0.029 units per kg per hr) and glucagon (2.86 micrograms per kg per hr) daily; Group V (n = 10) received a continuous infusion of parenteral amino acids (Travasol), and Group VI (n = 9) received daily intramuscular methylprednisolone (0.69 mg per kg). In each case, treatment was initiated 16 hr following galactosamine injection. Serum aminotransferase activity was determined on Days 0, 1, 4 and 10 of the 10-day study. Liver histology was obtained immediately after death and graded under code on a scale of 1 to 4 for severity of hepatitis. Rabbits surviving 10 days were sacrificed on Day 10 for histologic examination. The extent of galactosamine-induced hepatic injury was similar in all six groups as manifest by peak mean SGPT (range: 2,662 to 3,568 IU per liter), SGOT (range: 4,435 to 5,625 IU per liter) levels and hepatic histologic findings. The overall survival rate in controls was 6/27 (22%); in insulin/glucagon-treated animals 2/9 (22%), and in the amino acid-treated group 2/10 (20%).(ABSTRACT TRUNCATED AT 250 WORDS)