Biomedical subjects

Laurent Givalois

Publications and source records attributed to Laurent Givalois.

6 recordsLinked to original sources

PubMed2006

Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo.

Brain-derived neurotrophic factor (BDNF) has been extensively studied in the central nervous system as a survival and differentiation factor and in plasticity processes. In vitro, BDNF has been shown to stimulate cellular differentiation and neurohormones synthesis and release. We demonstrated that BDNF is a potent and specific stimulatory agent of somatostatin (SRIH) synthesis in primary cultures of hypothalamic neurons. However, less information is available about its function on SRIH neurons in vivo. In the present study, we examined the effect of in vivo intracerebroventricular BDNF administration in adult non-anesthetized male rats. Two distinct experimental approaches were used: acute intracerebroventricular injection and long-term (14 days) continuous infusion (Alzet micro-pumps). We demonstrate that single intracerebroventricular BDNF injections (5 microg/rat) induce an early (60 and 180 min) decrease in the SRIH mRNA signal in the hypothalamic periventricular nucleus (PeVN) accompanied by a decrease of the hypothalamic SRIH content. 48 h after the acute injection, SRIH mRNA levels and peptide content strongly and significantly increased. After continuous intracerebroventricular BDNF administration (12 microg/day for 14 days), a significant increase in the SRIH hypothalamic content was observed. Nevertheless, the increase in peptide content was not correlated with a similar increase in the PeVN messenger level. These findings show the involvement of BDNF in the in vivo regulation of somatostatinergic neurons in adult rats, which clearly differs according to the BDNF administration mode.

Animals↗

PubMed2004

Expression of brain-derived neurotrophic factor and its receptors in the median eminence cells with sensitivity to stress.

The median eminence (ME) is considered as the final common pathway connecting the nervous and endocrine systems. In this neurohemal structure, dynamic interactions among nerve terminals, tanycytes, and astrocytes determine through plastic processes the neurohormones access to the portal blood. Because brain-derived neurotrophic factor (BDNF) is involved in plastic changes, we investigated its presence and that of its receptors (TrkB) in the different cellular types described in the ME. Using in situ hybridization and immunohistochemical techniques, we demonstrated that BDNF immunoreactivity was essentially located in the astrocytes and to a lesser extent in tanycytes. By contrast, BDNF was not detected in nerve terminals reaching the external layer of the ME. TrkB antibodies recognizing the extracellular receptor domain labeled all of these different cell types, suggesting an autocrine or paracrine action of BDNF at this level. More selective antibodies showed that TrkB.FL immunostaining was found in tanycytes and nerve endings, whereas TrkB.T1 immunostaining was localized in all cellular types. Immobilization stress increased BDNF mRNA and BDNF immunoreactivity patterns and induced biphasic BDNF release from the ME, as analyzed by push-pull perfusion. In addition, we observed that 60-min stress intensified BDNF immunoreactivity in the internal layer and also its colocalization with glial fibrillary acidic protein. Stress also accentuated BDNF immunostaining in the perivascular space in elements that were not labeled with antibodies recognizing fibroblast or endothelial cells. These data disclosed a novel location of BDNF and its receptors in the ME, which are presumably involved in dynamic processes such as hormone release.

Animals↗

PubMed2004

A single brain-derived neurotrophic factor injection modifies hypothalamo-pituitary-adrenocortical axis activity in adult male rats.

Immobilization stress induces in adult male rats rapid activation of brain derived neurotrophic factor (BDNF) expression in the hypothalamic paraventricular nucleus (PVN) preceding the increases in corticotropin releasing hormone (CRH) and arginin-vasopressin (AVP) expression. The BDNF mRNA signal belatedly co-localizes with CRH and AVP mRNA signals in the PVN, as determined by in situ hybridization. Intracerebroventricular BDNF injections (5 microg/rat) in non-anesthetized adult male rats induce a gradual increase in the CRH mRNA signal whereas AVP mRNA signal progressively decreases in the parvocellular and magnocellular PVN portions. At the same time, the CRH hypothalamic content decreases while the AVP content increases. These variations are accompanied by increases in ACTH and corticosterone plasma concentrations. These results strongly suggest that BDNF could be a stress-responsive intercellular messenger since when it is exogenously administered acts as an important and early component in the activation and recruitment of hypothalamic CRH and AVP neurons.

Adrenocorticotropic Hormone↗

PubMed2004

Physiology of BDNF: focus on hypothalamic function.

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family which interacts with high-affinity protein kinase receptors (Trk) and the unselective p75(NGFR) receptor. The BDNF gene has a complex structure with multiple regulatory elements and four promoters that are differentially expressed in central or peripheral tissue. BDNF expression is regulated by neuronal activity or peripheral hormones. Neurotrophins regulate the survival and differentiation of neurons during development but growing evidence indicates that they are also involved in several functions in adulthood, including plasticity processes. BDNF expression in the central nervous system (CNS) is modified by various kinds of brain insult (stress, ischemia, seizure activity, hypoglycemia, etc.) and alterations in its expression may contribute to some pathologies such as depression, epilepsy, Alzheimer's, and Parkinson's disease. Apart from very traumatic situations, the brain functioning is resilient to stress and capable of adaptive plasticity. Neurotrophins might act as plasticity mediators enhancing this trait which seems to be crucial in adaptive processes. In addition to documenting all of the topics mentioned above in the CNS, we review the state of the art concerning neurotrophins and their receptors, including our personal contribution which is essentially focused on the stress response.

Animals↗

PubMed2003

Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats.

Brain-derived neurotrophic factor (BDNF) is strongly expressed in the hippocampus, where it has been associated with memory processes. In the central nervous system, some learning processes, as well as brain insults, including stress, induce modifications in BDNF mRNA expression. Because stress and memory appear to share some neuronal pathways, we studied BDNF mRNA and BDNF peptide variations in response to short times of immobilization stress. Using an RNase protection assay, we demonstrated that short-time stress application induced a significant increase (at 60 min) in BDNF mRNA levels in the whole rat hippocampus. Changes in BDNF mRNA content appear to reflect increased expression of BDNF transcripts containing exons I, II, and III, that were also significantly modified at this time. The time course of stress-induced changes in BDNF transcript levels revealed that mRNA containing exon III was the first increased, significantly elevated by 15 min, attaining maximal levels at 60 min, as BDNF transcripts containing exons I and II. However, at longer times of stress (180 min), BDNF mRNA levels were decreased as well as mRNA containing exon IV. In situ hybridization analysis of discrete hippocampal layers demonstrated that BDNF mRNA expression increased as early as 15 min in most hippocampal regions, with no modification in the number of labeled cells. The same signal pattern, although less pronounced, was determined at 60 min, but at this time a significant increase in BDNF-positive cells was visualized in the CA3 layer. The peptide, measured by immunoassay, was significantly augmented after 180 min of stress exposure whereas at 300 min, levels were similar to those measured in control animals. These data suggest that rapid changes in BDNF expression may be part of a compensatory response to preserve hippocampal homeostasis or a form of neuronal plasticity to cope with new stimuli.

Animals↗

PubMed2002

Central nitric oxide regulation of the hypothalamic-pituitary-adrenocortical axis in adult male rats.

The presence of nitric oxide (NO) synthase (NOS) in hypothalamic structures which control the activity of the pituitary-adrenocortical axis suggests that NO might be involved in the central regulation of ACTH secretion. We have studied the involvement of NO in the activity of the hypopothalamic-pituitary-adrenocortical (HPA) axis in intact and adrenalectomized rats. The acute effects (4 h) of two NOS inhibitors (HP-228 and NMMA), injected into the left lateral cerebral ventricle of freely moving male rats, on hypothalamic CRH and pituitary proopiomelacortin (POMC) mRNA levels as well as ACTH plasma levels were evaluated. In intact rats, HP-228, but not NMMA, induced an increase in CRH mRNA levels, while in adrenalectomized animals, both NOS inhibitors were effective in increasing CRH mRNA. In intact and adrenalectomized rats, both NOS inhibitors induced an increase in anterior pituitary POMC mRNA levels. Plasma ACTH levels were significantly elevated from 30 min to 2 h following the administration of either HP-228 or NMMA. In adrenalectomized animals, both NOS inhibitors produced a much striking increase of plasma ACTH levels which were still significantly increased at the longest time-interval studied. These results suggest that the central NO system exerts a tonic negative influence on the activity of the HPA axis in the presence or absence of circulating glucocorticoids.

Adrenal Cortex↗