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J F López

Publications and source records attributed to J F López.

16 recordsLinked to original sources
PubMed2000

Maternal deprivation regulates serotonin 1A and 2A receptors in the infant rat.

UNLABELLED: Several studies have demonstrated that 5-HT1A and 5-HT2A receptors are altered in rat brain following chronic stress. While this is true in the adult animal, this may be different in the developing animal, which has a limited corticosterone response to acute challenges between days 3 and 14 of life. METHODS: We investigated the effect of maternal deprivation on 5-HT2A and 5-HT1A receptor mRNA levels in the developing brain. In situ hybridization was used to quantify gene expression in rat pups at three ages: 6, 9, and 12 days old. In each age group, half were maternally deprived for 24 h and half were kept with their mothers. Maternally deprived animals showed elevated ACTH and corticosterone plasma levels when compared to NDEP animals, significantly elevated 5-HT1A mRNA levels in the CA1 hippocampal region and, significantly elevated 5-HT2A mRNA levels in the parietal cortex. No changes were observed in 5-HT1A or 5-HT-transporter mRNA levels in the dorsal raphe. Our results indicate that post-synaptic 5-HT receptors in the developing hippocampus and cortex are sensitive to maternal deprivation. Because hippocampal 5-HT1A gene expressions are known to decrease in the adult animal after chronic glucocorticoid elevation, this data also suggests that other mechanisms, perhaps central, predominate during development.

Adrenocorticotropic Hormone↗
PubMed2000

Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors.

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 microg/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.

Adrenal Cortex↗
PubMed1999

Neural circuits mediating stress.

Stress has been linked to the pathophysiology and pathogenesis of mood and anxiety disorders. Over the past few years, our understanding of the brain and neuroendocrine circuits that are linked to the stress response have increased dramatically. This article reviews a series of animal and human studies aimed at understanding what are the pathways by which stress is perceived, processed, and transduced into a neuroendocrine response. We focus on the classic stress circuit: the limbic-hypothalamic-pituitary-adrenal (LHPA) axis. These studies indicate that the LHPA stress circuit is a complex system with multiple control mechanisms and that these mechanisms are altered in pathological states, such as chronic stress and depression. These studies also suggest that the interactions between the LHPA and other neurotransmitters, such as serotonin, may provide the neurobiological substrate by which stress may affect mood.

Brain↗
PubMed1999

Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress.

BACKGROUND: When rats are subjected to chronic stress for 2 weeks, a significant decrease in hippocampal serotonin (5-HT)1A messenger RNA (mRNA) is observed. We wanted to investigate whether stress, administered for shorter periods of time, would result in decreases in 5-HT1A gene expression in hippocampus. METHODS: In one experiment, rats were either stressed daily for 1 week or implanted with two corticosterone pellets to produce elevated corticosterone levels. In another experiment, rats were subjected to a severe acute stressor and sacrificed 1 day or 1 week after the stressor. RESULTS: We found that 24 hours after the acute stress, rats showed a significant decrease in 5-HT1A mRNA levels in CA1 and the dentate gyrus compared to controls. No significant changes in 5-HT1A mRNA levels were detected in any of the other groups. CONCLUSIONS: Although 1 week of chronic stress is not sufficient to cause significant decreases in hippocampal 5-HT1A mRNA levels, a severe and prolonged acute stress is capable of down-regulating, at least transiently, 5-HT1A mRNA gene expression in hippocampus.

Acute Disease↗
PubMed1999

Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder.

Hippocampal glucocorticoid receptors (GR and MR) play an important role in glucocorticoid negative feedback. Abnormalities in negative feedback are found in depression and in post-traumatic stress disorder (PTSD), suggesting that GR and MR might be involved in the pathophysiology of these disorders. Enhanced negative feedback, the PTSD-specific neuroendocrine abnormality, can be induced in animals using a single prolonged stress (SPS) paradigm (a number of different stressors in one prolonged session, 'no stress' interval and a testing session one week later). In the current study, we examined hippocampal GR and MR mRNA distribution in the same animals that exhibited altered negative feedback following the SPS. Seven groups of adult Sprague-Dawley male rats (seven animals each) were used in two studies, comparing unstressed controls to acutely stressed animals (SPS: 24 h group), SPS animals (seven and 14 days), and SPS + chronic stress animals. GR and MR mRNA distribution across hippocampal subfields was studied using in-situ hybridization with 35S-labelled cRNA probes. Acute stress produced down-regulation of GR and MR mRNA across all hippocampal subfields. Seven days later (SPS-7 group), there was a differential recovery, with GR mRNA reaching higher than the prestress levels, and MR mRNA remaining down-regulated. The same differential regulation was present in the 14-day group. Chronically stressed animals that exhibited normal fast feedback also had normalization in their GR and MR mRNA levels. The MR/GR ratio was decreased only in animals that had enhanced fast feedback. These findings suggest that the increase in GR, in hippocampus is involved in the fast feedback hypersensitivity observed in the SPS animals, and might also underlie enhanced dexamethasone sensitivity found in PTSD. Since differential activation of GR and MR can modulate memory, behavioural responsivity, anxiety and fear, change in MR/GR ratio might also explain other PTSD-related phenomena.

Animals↗
PubMed1998

A.E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression.

BACKGROUND: Disturbances of the limbic-hypothalamic-pituitary-adrenal axis and the serotonin system are commonly found in depressive illness. Studying the effect of stress on these two neurobiological systems may give us important clues into the pathophysiology of affective illness and help us understand how stress and mood disorders are related. METHODS: We studied the effect of chronic unpredictable stress and antidepressant treatment on serotonin 1A (5-HT1A), glucocorticoid (GR), anti mineralocorticoid (MR) receptor levels in rat hippocampus, using in situ hybridization and receptor autoradiography. We also used in situ hybridization to quantify hippocampal 5-HT1A, GR, and MR messenger (mRNA) levels in a small group of suicide victims with a history of depression, compared to matched controls (n = 6). RESULTS: We found that rats subjected to chronic unpredictable stress showed a significant elevation of basal plasma corticosterone compared to nonstressed rats. Chronic stress also caused a decrease in 5-HT1A mRNA and binding in the hippocampus. In addition, chronic stress produced alterations on the MR/GR mRNA ratio in this same region. The decreases in 5-HT1A mRNA and binding, as well as the MR/GR alterations, were prevented in animals that received imipramine or desipramine antidepressant treatment. Zimelidine was unable to reverse stress-induced increases in corticosterone, and was only partially successful in preventing the stress-induced receptor changes in the hippocampus. Suicide victims with a history of depression showed changes that were very similar to the changes found in chronic stress. CONCLUSIONS: Alterations in hippocampal 5-HT1A levels and in the MR/GR balance may be one of the mechanisms by which stress may trigger and/or maintain depressive episodes.

Adrenalectomy↗
PubMed1998

Alpha, beta, and gamma mineralocorticoid receptor messenger ribonucleic acid splice variants: differential expression and rapid regulation in the developing hippocampus.

Two different types of corticoid receptor molecules bind circulating corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in the rat, corticosterone. During development, low corticosterone levels influence neurogenesis, and these effects are probably MR mediated. Three MR complementary DNA clones, alpha, beta, and gamma, have been identified in the rodent. All of these MR complementary DNA clones have identical coding regions, but differ significantly at the 5'-untranslated end. Although the functional significance of these three messenger RNA (mRNA) species remains unknown, one hypothesis is that they reflect the ability of the brain to regulate the expression of MR, allowing multiple factors to differentially control transcription in a tissue- and time-specific manner. To investigate this possibility, we examined the presence of these distinct mRNA forms in the developing rat hippocampus (HC). In situ hybridization with specific alpha, beta, and gamma complementary RNA probes was performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We found that there is differential expression of these forms in each of the HC subfields from infancy to adulthood. y expression appears to be associated with periods of cell birth and increased axonal sprouting. beta expression, on the other hand, may be best linked to periods of synaptogenesis, growth of commissural and associative terminal fields, and possibly active pruning. To explore the possibility that the differential gene expression may be related to corticosterone environment, adrenalectomy was performed. A rapid modulation of the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These findings suggest that the variation in expression and regulation during development of the multiple MR transcripts could reflect a complex pattern of developmental regulation that may involve a multitude of factors unique to each postnatal age and to the different neuronal populations within the hippocampal formation.

Adrenalectomy↗
PubMed1997

Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide.

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.

Adrenal Cortex Hormones↗
PubMed1996

Expression of serotonin transporter mRNA in human brainstem raphe nuclei.

The distribution of the messenger RNA (mRNA) encoding the serotonin transporter was investigated in the entire extent of the ascending raphe systems of the human brainstem, using a sensitive cRNA probe. This mRNA is abundant in the neurons of the raphe nuclei, especially in the dorsal and median raphe. The subregional distribution of this mRNA closely corresponds to that described for tryptophan hydroxylase in immunocytochemical studies. It is expressed at the highest levels in ventral and ventrolateral subregions of the dorsal raphe, with lower levels of expression in the median raphe, oral pontine reticular nuclei, and the supralemniscal cell groups. These results provide a description of the distribution of this mRNA in normal subjects and will serve as the basis for future studies of the subregional distribution of this mRNA in the brains of depressed patients and those who have committed suicide.

Adult↗
PubMed1995

Comparison of in-hospital mortality from myocardial infarction in the pre- and post-thrombolysis eras at the Royal University Hospital, Saskatoon, Saskatchewan.

PURPOSE: To compare in-hospital mortality of acute myocardial infarction (AMI) in two groups of patients in the pre- (1978-79) and post- (1990-91) thrombolysis era via a retrospective study. DATA SOURCE: Hospital files of patients discharged from the Royal University Hospital (RUH) in Saskatoon, Saskatchewan with the diagnosis of AMI. RESULTS: The diagnosis of AMI was established in 125 patients in 1978-79 and in 164 patients in 1990-91. The two groups were comparable with exceptions noted in the recorded family history of myocardial infarction and hypercholesterolemia. The overall in-hospital mortality decreased from 21.6% (1978-79) to 11.0% (1990-91; P = 0.05). The difference was more significant for patients admitted directly to the RUH, 24.0% (1978-79) versus 7.0% (1990-91; P = 0.05), and for patients over the age of 70 years. Marked differences were observed in the treatments provided to patients between these two decades. CONCLUSIONS: The in-hospital mortality of patients with AMI has decreased considerably in the past two decades. The use of thrombolytic agents, acetylsalicylic acid, heparin and beta-blockers may have contributed to these changes. A worse prognosis was observed with advancing age, hypotension on admission and the development of congestive heart failure, malignant arrhythmias or shock.

Age Factors↗
PubMed1994

Regulation of hippocampal 5-HT1A receptor gene expression by dexamethasone.

The effect of dexamethasone, a selective GR agonist, on hippocampal, 5-HT1A receptor mRNA expression and 5-HT1A binding was examined using in situ hybridization histochemistry and in vitro receptor autoradiography. One week after adrenalectomy, both 5-HT1A receptor mRNA expression and 5-HT1A binding were increased throughout the hippocampus. Administration of dexamethasone at the time of adrenalectomy significantly attenuated the increases in 5-HT1A mRNA expression in all hippocampal subfields (p < .05, Fisher Test), although 5-HT1A mRNA levels remained significantly higher than sham levels in all subfields with the exception of CA1. However, 5-HT1A binding levels were responsive to dexamethasone administration only within particular hippocampal subfields, CA1, and dentate gyrus. We conclude that GR occupation negatively regulates 5-HT1A receptor mRNA expression within the hippocampus and that 5-HT1A receptor sites are most sensitive to modulation in those hippocampal subfields expressing higher levels of GR receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims.

Suicidal behavior has been associated with hypothalamic-pituitary-adrenal overactivity in humans, as measured by increased corticosteroid secretion. To investigate whether this overactivity is reflected at the pituitary level, we have studied the localization of pro-opiomelanocortin (POMC) mRNA, and glucocorticoid receptor (GR) mRNA, in human anterior pituitaries, and quantified these messages relative to controls. Pituitaries from 7 suicide victims and 11 cardiac deaths were sectioned into 10-microns slides, stained with thionin and processed for in situ hybridization using a riboprobe complementary to human POMC mRNA. To correct for possible postmortem cell loss, hybridization with P1B15, a cDNA complementary to rat cyclophillin mRNA, was used in adjacent sections. POMC mRNA containing cells were found to be localized in clusters and were highly associated with corticotropin-releasing hormone (CRH) receptors. In contrast, GR mRNA containing cells were distributed through the pituitary, although areas of increased density were associated with POMC mRNA cells. Quantification with a computerized image analysis system revealed a 25% increase in POMC message in suicide victims. Analysis of the corticotrophic cell clumps showed that the suicide victims had higher POMC mRNA density per cell (p = 0.04) and larger corticotrophic cell size (p = 0.04) than the cardiac death victims. No differences in GR mRNA were detected between the two groups, although GR and POMC mRNA levels were highly and significantly correlated (r = 0.8, p < 0.001). There were no differences in P1B15 message between the two groups. We conclude that in situ hybridization is a useful tool to study gene regulation in human neuroendocrine tissue and that suicide victims show evidence of chronic hypothalamic-pituitary-adrenal axis activation.

Adult↗
PubMedDate not supplied

[Neurocardiogenic syncope in children].

Between december of 1994 and june 1997, 90 children and adolescents were referred to the Shaio Clinic Foundation for evaluation of recurrent unexplained syncope. Head-up tilt testing was positive in 45 (50%), 23 male, with a mean age of 12.7 years (range 5-17 years). The response during Head-up tilt testing was predominantly vasodepressor (57%), followed by mixed in 24% and cardioinhibitory in the remaining 17%. The majority of patients had a positive response during pharmacological phase with isoproterenol infusion at a mean time of 17 +/- 8 minutes. Head-up tilt is a safe diagnostic test and defines the cause of unexplained syncope in up to 50% of children and young adults with recurrent syncope. The management was based on education, control of risk factors and psychological and/or physical rehabilitation. In the 15.2 months follow up we observed complete remission or a significant reduction of symptoms in 95% of the cases. Only 5% of the patients persisted or had worsening of their symptoms.

Adolescent↗