Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats Following Acute Corticosterone Administration.

We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection, and after 6 h, hippocampi were collected for miRNA, mRNA, and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi.

Deletion of hippocampal Glucocorticoid receptors unveils sex-biased microRNA expression and neuronal morphology alterations in mice.

Sex differences in the brain have prompted many researchers to investigate the underlying molecular actors, such as the glucocorticoid receptor (GR). This nuclear receptor controls gene expression, including microRNAs (miRNAs), in non-neuronal cells. Here, we investigated sex-biased effects of GR on hippocampal miRNA expression and neuronal morphology by generating a neuron-specific GR knockout mouse ( ).

Loss of Social/Non-social Context Discrimination by Movement Acceleration in the Valproate Model of Autism.

Autism spectrum disorder (ASD) is a neurodevelopmental alteration characterized by social/communicative deficits, repetitive/stereotyped movements, and restricted/obsessive interests. However, there is not much information about whether movement alterations in ASD comprise modifications at the basic kinematic level, such as trajectory and velocity, which may contribute to the higher level of processing that allows the perception and interpretation of actions performed by others, and hence, impact social interaction. In order to further explore possible motor alterations in ASD, we analyzed movement parameters in the Valproate (VPA) animal model of autism.

Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats.

Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions.

Poloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia.

Loperamide is a μ-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional μ-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188).

Region-Specific Reduction of BDNF Protein and Transcripts in the Hippocampus of Juvenile Rats Prenatally Treated With Sodium Valproate.

Autism is a neurodevelopmental disorder characterized by a deep deficit in language and social interaction, accompanied by restricted, stereotyped and repetitive behaviors. The use of genetic autism animal models has revealed that the alteration of the mechanisms controlling the formation and maturation of neural circuits are points of convergence for the physiopathological pathways in several types of autism. Brain Derived Neurotrophic Factor (BDNF), a key multifunctional regulator of brain development, has been related to autism in several ways.

A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages.

Oral bioavailability of loperamide is restricted by its limited absorption in the gastrointestinal tract due to its poor aqueous solubility and its P-glycoprotein (Pgp) substrate characteristic. In addition, ammonium methacrylate copolymers have shown to have mucoadhesive properties, whereas poloxamer 188, has been suggested as a Pgp inhibitor. Thus, in this work, we evaluate conditions that affect physicochemical parameters of ammonium methacrylate/poloxamer 188-based nanocarriers loaded with loperamide hydrochloride.

Hippocampal Memory Recovery After Acute Stress: A Behavioral, Morphological and Molecular Study.

Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated-at the same time-the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in -methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits.

MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology.

Studies conducted in rodents subjected to chronic stress and some observations in humans after psychosocial stress, have allowed to establish a link between stress and the susceptibility to many complex diseases, including mood disorders. The studies in rodents have revealed that chronic exposure to stress negatively affects synaptic plasticity by triggering changes in the production of trophic factors, subunit levels of glutamate ionotropic receptors, neuron morphology, and neurogenesis in the adult hippocampus. These modifications may account for the impairment in learning and memory processes observed in chronically stressed animals.

Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress: Variation in Its Levels and Activity Distribution in Rat Hippocampus.

A single stress exposure facilitates memory formation through neuroplastic processes that reshape excitatory synapses in the hippocampus, probably requiring changes in extracellular matrix components. We tested the hypothesis that matrix metalloproteinase 9 (MMP-9), an enzyme that degrades components of extracellular matrix and synaptic proteins such as β-dystroglycan (β-DG), changes their activity and distribution in rat hippocampus during the acute stress response. After 2.

Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats.

Previous studies in rats have demonstrated that chronic restraint stress triggers anhedonia, depressive-like behaviors, anxiety and a reduction in dendritic spine density in hippocampal neurons. In this study, we compared the effect of repeated stress on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits in dorsal and ventral hippocampus (VH). Adult male Sprague-Dawley rats were randomly divided into control and stressed groups, and were daily restrained in their motion (2.

Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains.

Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics and mechanisms involved in this process using immobilized MBP and found that Pg activation by t-PA is significantly stimulated by MBP.

What Do We Really Know About 5-HT Receptor Signaling in Neuronal Cells?

Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT receptor (5-HTR), specially contrasting with those findings obtained in neuronal cells.

The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus.

Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase.

Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases.

Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study.

Background: Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients.

Methods: The diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.

Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons.

Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development.

Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study.

Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression.

Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide.

Background & Aims: Gold nanoparticles (GNPs) have promising applications for drug delivery as well as for the diagnosis and treatment of several pathologies, such as those related to the CNS. However, GNPs are retained in a number of organs, such as the liver and spleen. Owing to their negative charge and/or processes of opsonization, GNPs are retained by the reticuloendothelial system, thereby decreasing their delivery to the brain.

Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection.

Extracellular signal-regulated kinases (ERKs) are widely implicated in multiple physiological processes. Although ERK1/2 has been proposed as a common mediator of antidepressant action in naive rodents, it remains to be determined whether the ERK1/2 pathway plays a role in depressive disorder. Here, we investigated whether chronic restraint stress (14 days) and antidepressant treatment [desipramine (DMI), 10 mg/kg intraperitoneally] induce changes in animal behavior and hippocampal levels of phospho-ERK1/2 and its substrate phospho-cAMP response element-binding protein (CREB).

Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary.

Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats.

Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor beta1 (TGF-beta1) in hippocampus: effect of a TGF-beta1 oligo-antisense.

Background: Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor beta1 (TGF-beta1). Thus, we have investigated whether TGF-beta1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-beta1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats.

Perindopril regulates beta-agonist-induced cardiac apoptosis.

Administration of the beta-adrenergic agonist isoproterenol results in cardiac apoptosis. The effect of short-term beta-adrenergic stimulation by isoproterenol on the activity of plasma, lung, and left ventricular (LV) angiotensin I-converting enzyme (ACE) activity and its association with the development of cardiac apoptosis was investigated. beta-Adrenergic stimulation for 24 hours produced an early increase only in the proapoptotic proteins bax and bcl-XS without changes in the levels of the antiapoptotic protein bcl-XL.