Biomedical subjects

Juan F López

Publications and source records attributed to Juan F López.

5 recordsLinked to original sources

PubMed2006

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: effect of maternal deprivation.

Early in life, there is a delicate and critical balance aimed to maintain low hormone responses derived from the stress responsive hypothalamic-pituitary-adrenal axis (HPA). However, in the infant rat hypothalamic corticotrophin-releasing hormone (CRH) stress responses to environmental events are clearly seen even though other elements of the HPA axis may have limited responses. In view of the role of CRH in mediating behavior associated with stress and anxiety, we considered the ontogeny and the effects of prolonged maternal deprivation (DEP) in brain areas that express CRH-related molecules outside the hypothalamus. We hypothesized that DEP would alter the ontogeny of CRH, CRH binding protein and CRH receptor 1 in prefrontal cortex, amygdala, septum and hippocampus, areas that are part of the CRH extra hypothalamic system, and that a differential modulation would be observed in response to restraint. We compared non-deprived animals to animals subjected to 24 h of DEP at 6, 12 and 18 days of life. We found (1) developmental patterns, which were idiosyncratic to the anatomical area examined, and (2) a temporal response of mRNA levels which was also site specific. The genomic changes are not always related to maternal deprivation status, in fact DEP enhanced, suppressed or had no consequence on the underlying ontogenic progression and restraint response of these CRH-related molecules. We conclude that the extra hypothalamic CRH system is a dynamic system responding to developmental and environmental demands challenging the basic assumption of stress hypo responsiveness in the infant rat. This modulation may have important repercussions on morphological organization and events leading to neuroprotection.

Aging↗

PubMed2004

Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia.

BACKGROUND: Alterations of serotonin neurotransmission are implicated in both mood disorders and schizophrenia. Specific serotonin-receptor-based abnormalities in these psychiatric illnesses have been intensively studied; however, it has been difficult to draw any conclusions because of a lack of consensus. These inconsistencies have most likely arisen from the unavailability of selective ligands. METHODS: Our study used in situ hybridization to quantify 5-HT(1A), 5-HT(1B), and 5-HT(2A) mRNA levels in the hippocampus (HC) and 5-HT(1A) and 5-HT(2A) mRNA levels in the dorsolateral prefrontal cortex (DLPFC) of subjects with a history of major depression disorder (MDD), bipolar disorder (BPD), schizophrenia, and a normal comparison group (15 subjects per group). RESULTS: In the DLPFC, there is a significant decrease in 5-HT(1A) mRNA of subjects with MDD and in 5-HT(2A) mRNA of subjects with BPD. Subjects with MDD have a significant decrease in 5-HT(1A) mRNA in the HC; subjects with BPD and schizophrenia had increased 5-HT(1B) mRNA levels and a significant decrease in 5-HT(2A) mRNA levels in the hippocampal formation. CONCLUSIONS: Alterations in 5-HT(1A,) 5-HT(1B), and 5-HT(2A) mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders.

Adult↗

PubMed2003

Impact of maternal deprivation on brain corticotropin-releasing hormone circuits: prevention of CRH receptor-2 mRNA changes by desipramine treatment.

Corticotropin-releasing hormone (CRH) acts within the brain and pituitary to coordinate the overall endocrinological and behavioral stress response. From postnatal day (PND) 4 to 14, the infant rat displays minimal adrenal response to mild stress. However, maternal deprivation alters the pituitary-adrenal system such that the infants become responsive to specific stimuli. We hypothesized that maternal deprivation would also affect CRH brain circuits. Since tricyclic antidepressants have been shown to decrease the adrenal response to stress in adult rats, we hypothesized that CRH-related changes induced by maternal deprivation would be prevented by this treatment. Thus, we investigated CRH-related molecules on animals that were maternally deprived on PND 13 compared with nondeprived animals. We found that maternal deprivation caused alterations in the gene expression of both CRH receptors (CRHr) 1 and 2 in specific brain regions, and that some of these effects were augmented by chronic isotonic saline injections. There was a significant increase in CRH, CRHr1, and r2 mRNA in the cortex. In amygdala, CRHr1 and r2 mRNAs were decreased. CRHr2 mRNA was also decreased in the ventromedial nucleus of the hypothalamus, whereas an increase was detected in the hippocampal pyramidal cells. One week of desipramine (DES) administration preceding the maternal deprivation event prevented all the deprivation-induced changes in CRHr2 mRNA, regardless of the direction of the original change. We also found that chronic injection treatments enhanced the adrenocortical response and improved the efficiency of negative feedback in maternal deprivation animals. These results demonstrate that maternal deprivation elicits modifications of CRH brain circuits in a site-specific manner, and that the regulation of CRHr2 gene expression is mediated by mechanisms different from those involved with the modulation of CRHr1 in the infant rat.

Animals↗

PubMed2002

Hot flushes.

Almost every woman and some men will encounter hot flushes during their lifetime. Despite the prevalence of the symptoms, the pathophysiology of hot flushes remains unknown. A decline in hormone concentrations might lead to alterations in brain neurotransmitters and to instability in the hypothalamic thermoregulatory setpoint. The most effective treatments for hot flushes include oestrogens and progestagens. However, many women and their physicians are reluctant to accept hormonal treatments. Women want non-pharmacological treatments but unfortunately such treatments are not very effective, and non-hormonal drugs are often associated with adverse effects. Results from recent studies showed that selective serotonin reuptake inhibitors and other similar compounds can safely reduce hot flushes. Moreover, the efficacy of these drugs provides new insight into the pathophysiology of hot flushes. In this critical review, we assess knowledge of the epidemiology, pathophysiology, and treatment of hot flushes.

Female↗

PubMedDate not supplied

Brain 5-HT receptor system in the stressed infant rat: implications for vulnerability to substance abuse.

Clinical and epidemiological studies have found an association between aversive experiences early in life and an increased risk for depression, anxiety and substance abuse. In order to elucidate the mechanisms by which adverse life events are translated into behavioral and psychological abnormalities, we used a rat model to study the impact of chronic injection and 24 h maternal deprivation on the developing rat brain. Specifically, we investigated the regulation of molecules related to the 5-HT (5-HT) system and studied the effect of desipramine administration on animals that were maternally deprived (DEP) on day 13 of life compared with non-deprived animals. We found that maternal deprivation caused an enhanced corticosterone response to an acute stress. Maternally deprived animals also showed a decrease in corticosteroid receptors and an increase in 5-HT 1A and 1B receptors restricted to the CA1 region of the hippocampus. Desipramine prevented the maternal deprivation induced up-regulation of the 5-HT 1B receptor and the enhanced adrenocortical response observed in these animals. Interestingly, non-deprived animals receiving chronic injections showed a decrease in hippocampal 5-HT1B receptor mRNA. At 80 days of age, a group of animals that were treated as infants were given the option of drinking from two identical water bottles, one bottle contained tap water, while the second contained ethanol at increasing concentrations. Animals that received chronic injections during the newborn period consumed more alcohol than those that were not injected. On the other hand, maternal deprivation did not have an impact on alcohol consumption. Alcohol preference has implications to the organism since studies of drug self-administration in laboratory animals have shown that ethanol ingestion is positively related to the use of other drugs, principally opioids and psychostimulants. Our findings suggest that the quality and/or chronicity of early life stressors can influence the neurobiological substrates that may trigger and/or predispose individuals to substance abuse in adulthood.

Adrenal Cortex↗