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1.
Neurobiol Stress ; 25: 100551, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37362419

ABSTRACT

Psychosocial stress has increased considerably in our modern lifestyle, affecting global mental health. Deficits in attentional control are cardinal features of stress disorders and pathological anxiety. Studies suggest that changes in the locus coeruleus-norepinephrine system could underlie the effects of stress on top-down attentional control. However, the impact of psychosocial stress on attentional processes and its underlying neural mechanisms are poorly understood. This study aims to investigate the effect of psychosocial stress on attentional processing and brain signatures. Evoked potentials and pupillary activity related to the oddball auditory paradigm were recorded before and after applying the Montreal Imaging Stress Task (MIST). Electrocardiogram (ECG), salivary cortisol, and subjective anxiety/stress levels were measured at different experimental periods. The control group experienced the same physical and cognitive effort but without the psychosocial stress component. The results showed that stressed subjects exhibited decreased P3a and P3b amplitude, pupil phasic response, and correct responses. On the other hand, they displayed an increase in Mismatch Negativity (MMN). N1 amplitude after MIST only decreased in the control group. We found that differences in P3b amplitude between the first and second oddball were significantly correlated with pupillary dilation and salivary cortisol levels. Our results suggest that under social-evaluative threat, basal activity of the coeruleus-norepinephrine system increases, enhancing alertness and decreasing voluntary attentional resources for the cognitive task. These findings contribute to understanding the neurobiological basis of attentional changes in pathologies associated with chronic psychosocial stress.

2.
J Neuroendocrinol ; 30(7): e12609, 2018 07.
Article in English | MEDLINE | ID: mdl-29772083

ABSTRACT

The foetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behaviour. The present study aimed to determine the physiological and behavioural effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 to 21, a critical period for foetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviours, as well as spontaneous social interaction. We also assessed maternal behaviours and 2 stress markers: basal vs acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behaviour, whereas both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation, as well as anxiety- and depressive-like behaviours, were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on hypothalamic-pituitary-adrenal (HPA) axis activity and on behaviour during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, and they were also more anxious and experienced depressive-like behaviours. These results are useful with respect to studying the neurobiological basis of childhood depression at a preclinical level.


Subject(s)
Anxiety/metabolism , Body Weight/physiology , Corticosterone/blood , Depression/metabolism , Prenatal Exposure Delayed Effects/metabolism , Stress, Physiological/physiology , Stress, Psychological/metabolism , Animals , Behavior, Animal/physiology , Female , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Restraint, Physical , Sex Factors
3.
Horm Metab Res ; 46(5): 322-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24323410

ABSTRACT

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 µl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 µl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter.


Subject(s)
Dopamine/metabolism , Estradiol/analogs & derivatives , Substantia Nigra/metabolism , Amphetamine/metabolism , Animals , Animals, Newborn , Corpus Striatum/growth & development , Corpus Striatum/metabolism , Estradiol/metabolism , Female , Motor Activity , Neurotransmitter Agents/metabolism , Rats , Rats, Sprague-Dawley , Substantia Nigra/growth & development
4.
Neuroscience ; 169(1): 98-108, 2010 Aug 11.
Article in English | MEDLINE | ID: mdl-20417256

ABSTRACT

It has been postulated that chronic administration of antidepressant drugs induces delayed structural and molecular adaptations at glutamatergic forebrain synapses that might underlie mood improvement. To gain further insight into these changes in the cerebral cortex, rats were treated with fluoxetine (flx) for 4 weeks. These animals showed decreased anxiety and learned helplessness. N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit levels (NR1, NR2A, NR2B, GluR1 and GluR2) were analysed in the forebrain by both western blot of homogenates and immunohistochemistry. Both methods demonstrated an upregulation of NR2A, GluR1 and GluR2 that was especially significant in the retrosplenial granular b cortex (RSGb). However, when analysing subunit content in postsynaptic densities and synaptic membranes, we found increases of NR2A and GluR2 but not GluR1. Instead, GluR1 was augmented in a microsomal fraction containing intracellular membranes. NR1 and GluR2 were co-immunoprecipitated from postsynaptic densities and synaptic membranes. In the immunoprecipitates, NR2A was increased while GluR1 was decreased supporting a change in receptor stoichiometry. The changes of subunit levels were associated with an upregulation of dendritic spine density and of large, mushroom-type spines. These molecular and structural adaptations might be involved in neuronal network stabilization following long-term flx treatment.


Subject(s)
Antidepressive Agents/pharmacology , Fluoxetine/pharmacology , Gene Expression Regulation/drug effects , Glutamic Acid/physiology , Neuronal Plasticity/drug effects , Prosencephalon/drug effects , Receptors, AMPA/biosynthesis , Receptors, N-Methyl-D-Aspartate/biosynthesis , Animals , Anxiety/drug therapy , Behavior, Animal/drug effects , Dendritic Spines/drug effects , Dendritic Spines/metabolism , Helplessness, Learned , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Male , Microsomes/drug effects , Microsomes/metabolism , Neurons/drug effects , Neurons/metabolism , Neurons/ultrastructure , Post-Synaptic Density/drug effects , Post-Synaptic Density/metabolism , Prosencephalon/metabolism , Rats , Rats, Sprague-Dawley , Receptors, AMPA/genetics , Receptors, N-Methyl-D-Aspartate/genetics , Synaptic Membranes/drug effects , Synaptic Membranes/metabolism
5.
Neuroscience ; 135(4): 1067-74, 2005.
Article in English | MEDLINE | ID: mdl-16165300

ABSTRACT

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.


Subject(s)
Behavior, Animal/physiology , Conditioning, Classical/physiology , Neurons/pathology , Stress, Psychological/pathology , Stress, Psychological/physiopathology , Acoustic Stimulation , Animals , Avoidance Learning/physiology , Male , Maze Learning/physiology , Photic Stimulation , Rats , Rats, Sprague-Dawley
6.
Neurotox Res ; 4(2): 161-3, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12829417

ABSTRACT

Monoamine oxidase-A (MAO-A) [amiflamine (AMF) and 4-methylthioamphetamine (MTA)] and MAO-B (L-deprenyl) inhibitors were found to be cytotoxic in a concentration-dependent manner for RCHT cells derived from adult rat hypothalamus. The cytotoxic effects were increased when the inhibitors were co-incubated with dicoumarol and especially with 25 micro M AMF+100 micro M dicoumarol (2.5-fold; P <0.001). The treatment of RCHT cells solely with AMF induced a marked decrease in the expression of DT-diaphorase mRNA.

7.
Biochem Biophys Res Commun ; 283(5): 1069-76, 2001 May 25.
Article in English | MEDLINE | ID: mdl-11355881

ABSTRACT

The endogenous dopamine-derived neurotoxin salsolinol was found to decrease survival in the dopaminergic neuronal cell line RCSN-3, derived from adult rat substantia nigra in a concentration-dependent manner (208 microM salsolinol induced a 50% survival decrease). Incubation of RCSN-3 cells with 100 micro;M dicoumarol and salsolinol significantly decreased cell survival by 2.5-fold (P < 0.001), contrasting with a negligible effect on RCHT cells, which exhibited nearly a 5-fold lower nomifensine-insensitive dopamine uptake. The levels of catalase and glutathione peroxidase mRNA were decreased when RCSN-3 cells were treated with 100 microM salsolinol alone or in the presence of 100 microM dicoumarol. In vitro oxidation of salsolinol to o-quinone catalyzed by lactoperoxidase gave the quinone methide and 1,2-dihydro-1-methyl-6,7-isoquinoline diol as final products of salsolinol oxidation as determined by NMR analysis. Evidence of the formation of salsolinol o-semiquinone radical has been provided by ESR studies during one-electron oxidation of salsolinol catalyzed by lactoperoxidase.


Subject(s)
Cell Survival/drug effects , Dopamine/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Indolequinones , Indoles/pharmacology , Isoquinolines/pharmacology , Neurons/drug effects , Quinones/pharmacology , Animals , Biological Transport/drug effects , Catalase/genetics , Cell Line , Dicumarol/pharmacology , Electron Spin Resonance Spectroscopy , Glutathione Peroxidase/genetics , Neurons/cytology , Neurons/metabolism , RNA, Messenger/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction , Substantia Nigra/cytology , Superoxide Dismutase/genetics , Transcription, Genetic/drug effects
8.
J Neurochem ; 77(2): 519-29, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11299314

ABSTRACT

The mechanism of copper (Cu) neurotoxicity was studied in the RCSN-3 neuronal dopaminergic cell line, derived from substantia nigra of an adult rat. The formation of a Cu-dopamine complex was accompanied by oxidation of dopamine to aminochrome. We found that the Cu-dopamine complex mediates the uptake of (64)CuSO(4) into the Raúl Caviedes substantia nigra-clone 3 (RCSN3) cells, and it is inhibited by the addition of excess dopamine (2 m M) (63%, p < 0.001) and nomifensine (2 microM) (77%, p < 0.001). Copper sulfate (1 m M) alone was not toxic to RCSN-3 cells, but was when combined with dopamine or with dicoumarol (95% toxicity; p < 0.001) which inhibits DPNH and TPNH (DT)-diaphorase. Electron spin resonance (ESR) spectrum of the 5,5-dimethylpyrroline-N-oxide (DMPO) spin trap adducts showed the presence of a C-centered radical when incubating cells with dopamine, CuSO(4) and dicoumarol. A decrease in the expression of CuZn-superoxide dismutase and glutathione peroxidase mRNA was observed when RCSN-3 cells were treated with CuSO(4), dopamine, or CuSO(4) and dopamine. However, the mRNA expression of glutathione peroxidase remained at control levels when the cells were treated with CuSO(4), dopamine and dicoumarol. The regulation of catalase was different since all the treatments with CuSO(4) increased the expression of catalase mRNA. Our results suggest that copper neurotoxicity is dependent on: (i) the formation of Cu-dopamine complexes with concomitant dopamine oxidation to aminochrome; (ii) dopamine-dependent Cu uptake; and (iii) one-electron reduction of aminochrome.


Subject(s)
Copper Sulfate/toxicity , Dopamine/pharmacology , Indolequinones , Indoles/metabolism , Ion Transport/drug effects , Neurons/drug effects , Substantia Nigra/cytology , Animals , Catalase/biosynthesis , Catalase/genetics , Cell Line , Copper Sulfate/metabolism , Copper Sulfate/pharmacology , Dicumarol/toxicity , Electron Spin Resonance Spectroscopy , Enzyme Induction/drug effects , Glutathione Peroxidase/biosynthesis , Glutathione Peroxidase/genetics , Metallothionein/metabolism , NAD(P)H Dehydrogenase (Quinone)/biosynthesis , NAD(P)H Dehydrogenase (Quinone)/genetics , Neurons/metabolism , Nomifensine/pharmacology , Oxidation-Reduction , Oxidative Stress , Parkinson Disease/metabolism , RNA, Messenger/biosynthesis , Rats , Superoxide Dismutase/biosynthesis , Superoxide Dismutase/genetics
9.
Mol Cell Biochem ; 212(1-2): 131-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11108144

ABSTRACT

Angiotensin receptor II mRNA was found to be expressed in dopaminergic neuronal cell line RCSN3 of rat substantia nigra using RT-PCR reaction. Aminochrome (150 microM), a metabolite of the dopamine oxidative pathway, was found to down regulate the expression of angiotensin receptor mRNA in RCSN3 cells by 83% (p < 0.05).


Subject(s)
Angiotensin II/metabolism , Gene Expression Regulation/drug effects , Indolequinones , Indoles/pharmacology , Neurons/metabolism , Receptors, Angiotensin/genetics , Receptors, Angiotensin/metabolism , Substantia Nigra/metabolism , Animals , Cell Line , Dihydrolipoamide Dehydrogenase/genetics , Neurons/cytology , RNA, Messenger/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction , Substantia Nigra/cytology , Transcription, Genetic/drug effects
10.
Amino Acids ; 18(4): 363-73, 2000.
Article in English | MEDLINE | ID: mdl-10949919

ABSTRACT

Aminochrome was found to be toxic in a mouse-derived neuronal cell line (CNh). The effect was concentration dependent (10-150microM). The issue whether aminochrome toxicity involves glutamate transmission was studied with several glutamate receptors antagonists. Incubation of the cells with aminochrome (150microM) in the presence of 100microM of the AMPA antagonist, NBQX resulted in an increase of cell survival, from 52 to 73%. However, this protective effect did not seem to be related to activation of ionotropic glutamate receptors since incubation of CNh cells with 200microM of glutamate resulted in only 10% decrease of cell survival. However, NBQX was found to inhibit in vitro the autoxidation process. One hundred microM AP-5 did not have any effect on aminochrome toxicity. The toxic effect of aminochrome on CNh cells seems to be dependent of extracellular activation since addition of dicoumarol, a specific inhibitor of DT-diaphorase, did not affect that toxicity, which can be explained perhaps by a lack of a transport system for aminochrome into the CNh cells.


Subject(s)
Dopamine/pharmacology , Indolequinones , Indoles/toxicity , Neurons/drug effects , Receptors, Glutamate/metabolism , Animals , Catalase/pharmacology , Cell Line , Cell Survival/drug effects , Cerebral Cortex/cytology , Dicumarol/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Free Radical Scavengers/pharmacology , Glutamic Acid/metabolism , Glutamic Acid/pharmacology , Mice , Models, Biological , NAD/metabolism , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism , Neurons/metabolism , Oxidation-Reduction , Quinoxalines/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Superoxide Dismutase/pharmacology , Uncoupling Agents/pharmacology
11.
Biochem Biophys Res Commun ; 274(1): 32-6, 2000 Jul 21.
Article in English | MEDLINE | ID: mdl-10903891

ABSTRACT

Human glutathione transferase M2-2 prevents the formation of neurotoxic aminochrome and dopachrome by catalyzing the conjugation of dopamine and dopa o-quinone with glutathione. NMR analysis of dopamine and dopa o-quinone-glutathione conjugates revealed that the addition of glutathione was at C-5 to form 5-S-glutathionyl-dopamine and 5-S-glutathionyl-dopa, respectively. Both conjugates were found to be resistant to oxidation by biological oxidizing agents such as O(2), H(2)O(2), and O(*-)(2), and the glutathione transferase-catalyzed reaction can therefore serve a neuroprotective antioxidant function.


Subject(s)
Benzoquinones/metabolism , Dihydroxyphenylalanine/analogs & derivatives , Dopamine/metabolism , Glutathione Transferase/metabolism , Indolequinones , Benzoquinones/chemistry , Cysteinyldopa/analogs & derivatives , Cysteinyldopa/metabolism , Dihydroxyphenylalanine/chemistry , Dihydroxyphenylalanine/metabolism , Dopamine/chemistry , Glutathione/metabolism , Glutathione Transferase/chemistry , Humans , Indoles/metabolism , Isoenzymes , Magnetic Resonance Spectroscopy , Models, Chemical , Oxidation-Reduction , Protein Binding , Quinones/metabolism , Time Factors
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