Abstract:
:The experiments described herein present a method for tracking diffusion of the glucocorticoid receptor agonist RU28362 in brain following i.c.v. drug administration. A useful property of glucocorticoid receptor is that it is primarily cytoplasmic when unbound and rapidly translocates to the nucleus when bound by ligand. Thus, removal of endogenous glucocorticoids by adrenalectomy allows us to identify brain regions with activated glucocorticoid receptor after i.c.v. glucocorticoid receptor agonist treatment by examining the presence or absence of nuclear glucocorticoid receptor immunostaining. We have previously demonstrated that an i.p. injection of 150 microg/kg RU28362 1 h prior to restraint stress is sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis hormone secretion [Ginsberg AB, Campeau S, Day HE, Spencer RL (2003) Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis hormone secretion and expression of corticotropin-releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 15:1075-1083]. We report here, however, that in rats i.c.v. treatment with a high-dose of RU28362 (1 microg) 1 h prior to stressor onset does not suppress stress-induced hypothalamic-pituitary-adrenal axis activity. We then performed a series of experiments to examine the possible differences in glucocorticoid receptor activation patterns in brain and pituitary after i.c.v. or i.p. treatment with RU28362. In a dose-response study we found that 1 h after i.c.v. injection of RU28362 (0.001, 0.1 and 1.0 microg) glucocorticoid receptor nuclear immunoreactivity was only evident in brain tissue immediately adjacent to the lateral or third ventricle, including the medial but not more lateral portion of the medial parvocellular paraventricular nucleus of the hypothalamus. In contrast, i.p. injection of RU28362 produced a uniform predominantly nuclear glucocorticoid receptor immunostaining pattern throughout all brain tissue. I.c.v. injection of the endogenous glucocorticoid receptor agonist, corticosterone (1 microg) also had limited diffusion into brain tissue. Time-course studies indicated that there was not a greater extent of nuclear glucocorticoid receptor immunostaining present in brain after shorter (10 or 30 min) or longer (2 or 3 h) intervals of time after i.c.v. RU28362 injection. Importantly, time-course studies found that i.c.v. RU28362 produced significant increases in nuclear glucocorticoid receptor immunostaining in the anterior pituitary that were evident within 10 min after injection and maximal after 1 h. These studies support an extensive literature indicating that drugs have very limited ability to diffuse out of the ventricles into brain tissue after i.c.v. injection, while at the same time reaching peripheral tissue sites. In addition, these studies indicate that significant occupancy of some glucocorticoid receptor within the paraventricular nucleus of the hypothalamus and pituitary is not necessarily sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis activity.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Francis AB,Pace TW,Ginsberg AB,Rubin BA,Spencer RLdoi
10.1016/j.neuroscience.2006.04.067subject
Has Abstractpub_date
2006-09-01 00:00:00pages
1503-15issue
3eissn
0306-4522issn
1873-7544pii
S0306-4522(06)00618-Xjournal_volume
141pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract::The findings reported in this work show that pretreatment with polyunsaturated fatty acids, particularly linolenic acid, present in vegetable oils, can provide a potent tolerance against neurodegeneration in two models of neuronal death-generating treatments such as kainic acid injection and global ischemia. Rats were...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(01)00473-0
更新日期:2002-01-01 00:00:00
abstract::Niemann-Pick Type C1 (NPC1) is an autosomal recessive disorder characterized by the accumulation of cholesterol and glycosphingolipids. Combination-treatment utilizing cyclodextrin, allopregnanolone and miglustat (CYCLO/ALLO/miglustat) can ameliorate NPC1 disease in a mutant mouse model. The present study was designed...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2013.08.001
更新日期:2013-11-12 00:00:00
abstract::Leptin microinjections into the nucleus of the solitary tract (NTS) have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex. In this study, experiments were done in Sprague-Dawley rats initially to provide a detailed mapping within the NTS co...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2012.10.065
更新日期:2013-01-15 00:00:00
abstract::The nucleus accumbens septi is the major target of mesolimbic dopamine neurons originating in the ventral tegmental area of the mesencephalon. Studies involving experimental manipulation of dopamine transmission by drugs and by lesions, as well as in vivo monitoring of extracellular dopamine concentrations, have provi...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00583-1
更新日期:1999-03-01 00:00:00
abstract::A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in s...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(00)00381-x
更新日期:2000-01-01 00:00:00
abstract::Neurosteroids are synthesized de novo in the brain and the cerebellar Purkinje cell is a major site for neurosteroid formation. We have demonstrated that the rat Purkinje cell actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2004.04.003
更新日期:2004-01-01 00:00:00
abstract::Intrauterine growth restriction is a risk factor for neurological and behavioural deficits in children although the precise underlying biological correlate for this is unclear. The present study shows that animals with intrauterine growth restriction, induced by a period of reduced placental blood flow during the seco...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(00)00271-2
更新日期:2000-01-01 00:00:00
abstract::Ciliary neurotrophic factor is known to exert both survival and differentiative actions on a number of neuronal populations of the peripheral and central nervous systems. In this study we have compared the trophic effects of ciliary neurotrophic factor and nerve growth factor on developing septal neurons of the rat in...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)00590-2
更新日期:1995-06-01 00:00:00
abstract::Fetal striatal neurons were transplanted into the ibotenic acid lesioned rat striatum. Three months after transplantation the grafted tissue was Golgi-impregnated and examined at the light microscopic level to determine the morphological characteristics of the transplanted neurons. Golgi-impregnated neurons were then ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(90)90104-c
更新日期:1990-01-01 00:00:00
abstract::The clinical differential diagnosis between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD) is difficult in early stages. To identify objective markers for differential diagnosis, we combined the novel tract-based spatial statistics (TBSS) and region of interest (ROI) analyses for...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.07.060
更新日期:2015-10-01 00:00:00
abstract::The prefrontal cortex is highly vulnerable to traumatic brain injury (TBI) and its structural and/or functional alterations as a result of TBI can give rise to persistent working memory (WM) dysfunction. Using a rodent model of TBI, we have described profound WM deficits following TBI that are associated with increase...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.10.048
更新日期:2011-01-13 00:00:00
abstract::Sestrin2 (Sesn2) is a stress response protein which expresses neuroprotective characteristics in some neurodegenerative disorders. However, the impact of Sesn2 on the clinical outcome of stroke is unclear. The nuclear factor-erythroid 2 related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway is a key factor in angiogene...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2019.05.005
更新日期:2019-07-01 00:00:00
abstract::Previous studies in our laboratories found that isolectin B(4)(IB(4))-positive polymodal nociceptors in the mouse do not express transient receptor potential vanilloid 1 (TRPV1), nor does deletion of TRPV1 compromise the ability of these afferents to detect thermal stimuli. Considering that IB(4)-positive afferents ac...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2006.02.015
更新日期:2006-06-19 00:00:00
abstract::Nerve growth factor (NGF) can augment transmitter release in sensory neurons by acutely sensitizing sensory neurons and by increasing the expression of calcitonin gene-related peptide (CGRP) over time. The current study examined the intracellular signaling pathways that mediate these two temporally distinct effects of...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.09.027
更新日期:2010-12-15 00:00:00
abstract::PACAP1-38, a ubiquitous and multifunctional regulator has been in the focus of neurotoxicity research due to its impressive neuroprotective potential. Although the literature extensively demonstrated its repressive effect on the apoptotic machinery in neurodegenerative models, there is a striking absence of analysis o...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2018.06.008
更新日期:2018-08-10 00:00:00
abstract::Development and differentiation of basal forebrain-derived cholinergic neurons were studied using a new technique that combines dissociated cell cultures with organotypic slice cultures. Slices of cerebral cortex or entire forebrain hemispheres were taken from early postnatal rat pups and maintained as organotypic cul...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(97)00067-5
更新日期:1997-10-01 00:00:00
abstract::The distribution of D1 dopamine receptors was studied autoradiographically in the basal ganglia of the cat, monkey and human. These receptor binding sites were labeled directly with the D1-selective antagonist [3H]SCH 23390, and ligand-binding assays were performed concurrently. Serial- or same-action analysis permitt...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(88)90130-3
更新日期:1988-07-01 00:00:00
abstract::The present experiments examined the effects of direct intracortical microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid directly into the insular cortex of rats, before or immediately after training of conditioned taste aversion and the water maze spatial learning task. In ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00360-1
更新日期:1999-03-01 00:00:00
abstract::Neurotoxicity of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), a potent agonist for metabotropic glutamate receptors negatively coupled to adenylyl cyclase, was investigated in vivo by the intraventricular administration in the rat, compared with that of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-C...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(96)00043-7
更新日期:1996-08-01 00:00:00
abstract::Bipolar disorder is a mood disorder characterized by impairing episodes of mania and depression. Twin studies have established that bipolar disorder is among the most heritable of medical disorders and efforts to identify specific susceptibility genes have intensified over the past two decades. The search for genes in...
journal_title:Neuroscience
pub_type: 杂志文章,评审
doi:10.1016/j.neuroscience.2009.03.080
更新日期:2009-11-24 00:00:00
abstract::Excitatory amino acid carrier 1 (EAAC1) is one important subtype of the excitatory amino acid transporters (EAATs), and its absence can increase the vulnerability to oxidative stress in neural tissue. Enhanced expression of EAAC1 can provide neuroprotection in multiple disorders, including ischemia and multiple sclero...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2016.01.027
更新日期:2016-04-05 00:00:00
abstract::A variety of postmortem brain studies and clinical investigations have provided evidence that reduced serotonin neurotransmission is associated with suicidal behavior and depression, and several serotonergic parameters have been found to be altered in the prefrontal cortex of suicide victims. However, the integrity of...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00289-0
更新日期:2002-01-01 00:00:00
abstract::The posterior parahippocampal gyrus (PPHG) of the non-human primate brain has a distinct dual role in cortical neural systems. On the one hand, it is a critical link in providing the entorhinal cortex and hippocampal formation with cortical input, while on the other hand it receives output from these structures and pr...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.03.077
更新日期:2008-06-23 00:00:00
abstract::Constraints involving the delivery method of glial cell line-derived neurotrophic factor (GDNF) have hampered its efficacy as a neuroprotectant in Parkinson's disease. Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), are genetically engineered to overexpress GDN...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.07.014
更新日期:2015-09-10 00:00:00
abstract::The glycine transporter GLYT2 is present in axonal boutons throughout the spinal cord, and its laminar distribution matches that of glycine-enriched axons, which are presumed to be glycinergic. In order to determine whether boutons which possess GLYT2 are glycine-enriched, we have carried out pre-embedding immunocytoc...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(96)00501-5
更新日期:1997-03-01 00:00:00
abstract::Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer's disease brain is characterized by neuritic plaques consisting of beta-amyloid peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18-interacting protein 1 and Munc18-interacting protein 2 mediate exocytosis and decreas...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.11.017
更新日期:2006-01-01 00:00:00
abstract::Membrane potential or ionic conductance of neurones of the mammalian central or peripheral nervous system maintained in vitro can be measured over periods of several hours. Drugs or transmitters which change potential or conductance can be applied repeatedly under equilibrium conditions, and pharmacological null metho...
journal_title:Neuroscience
pub_type: 杂志文章,评审
doi:10.1016/0306-4522(86)90070-9
更新日期:1986-04-01 00:00:00
abstract::Dephosphorylation by the Ca2+/calmodulin-dependent phosphatase calcineurin has been suggested as an important mechanism of Ca2+-dependent inactivation of voltage-gated Ca2+ channels. We have tested whether calcineurin plays a role in the inactivation process of two types of high-voltage-activated Ca2+ channels (L and ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(99)00434-0
更新日期:2000-01-01 00:00:00
abstract::Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-st...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2007.08.010
更新日期:2007-11-09 00:00:00
abstract::Depolarization-induced transmitter release in synaptosomes prepared from the hippocampus of aged rats is decreased compared with release from young animals. Although the underlying cause of this deficit is not known, some evidence suggests that increased membrane rigidity may contribute to these age-related synaptic c...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(99)00219-5
更新日期:1999-01-01 00:00:00