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1.
Neurobiol Learn Mem ; 93(3): 343-51, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19948234

ABSTRACT

The present study investigates the relationships between hippocampal corticosterone concentrations and memory retrieval performance in stress and non-stress conditions, in both young (6 month-old) and middle-aged (16 month-old) mice. For this purpose, the time-course evolution of stress-induced corticosterone rise in the dorsal hippocampus (dHPC) was investigated in both young and middle-aged mice. In parallel, the evolution of memory retrieval patterns was assessed using a contextual serial discrimination task (CSD). Finally, metyrapone (corticosterone synthesis inhibitor) was administered in order to evaluate the stress-induced impact of corticosterone rise on contextual memory retrieval in middle-aged animals. Results showed that: (i) non-stressed middle-aged mice exhibited a memory retrieval pattern opposite to that of non-stressed young animals, but similar to that of stressed young mice; (ii) the impact of stress on memory performance was transient (90 min) in young, as compared to middle-aged mice (120 min); (iii) dHPC basal (non-stress) corticosterone level was significantly increased by ageing; (iv) acute stress induced a rapid (15 min) and transient (90 min) dHPC corticosterone rise in young mice, while exhibiting greater magnitude and duration (120 min) in middle-aged animals; and (v) both the stress-induced endocrinal and memory effects were blocked by metyrapone in young and middle-aged mice. Finally, to our knowledge, the present work is the first study to directly measure the corticosterone rise in the hippocampus following exposure to stress and to directly correlate the corticosterone changes in the hippocampus with memory performance in both young and middle-aged mice.


Subject(s)
Aging/physiology , Corticosterone/adverse effects , Glucocorticoids/adverse effects , Hippocampus/drug effects , Memory Disorders/chemically induced , Stress, Psychological/psychology , Age Factors , Animals , Antimetabolites/pharmacology , Corticosterone/administration & dosage , Corticosterone/antagonists & inhibitors , Discrimination, Psychological/drug effects , Glucocorticoids/administration & dosage , Glucocorticoids/antagonists & inhibitors , Injections, Intraperitoneal , Male , Memory Disorders/diagnosis , Metyrapone/pharmacology , Mice , Mice, Inbred BALB C , Microdialysis , Time Factors
2.
Hippocampus ; 20(1): 196-207, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19360856

ABSTRACT

We previously showed that an acute stress (electric footshocks) induced both a rapid plasma corticosterone rise and a reversal of serial memory retrieval pattern in a contextual serial discrimination (CSD) task. This study is aimed at determining (i) if the rapid stress effects on CSD performance are mediated by the hippocampus; (ii) if hippocampal corticosterone membrane receptor activation is involved in the rapid stress effects on CSD performance. In experiment 1, microdialysis in the dorsal hippocampus (dHPC) was used to measure the stress-induced corticosterone rise; in parallel, the effect of acute stress on CSD performance was evaluated. In addition, the functional involvement of corticosterone in the behavioral effects of stress was assessed by administering metyrapone, a corticosterone synthesis inhibitor, before stress. In experiment 2, the involvement of hippocampal corticosterone membrane receptors in the stress-induced reversal of CSD performance was studied by injecting corticosterone-bovine serum albumin (BSA) (a membrane-impermeable complex) in the dHPC in non stressed mice. Results showed that (i) the acute stress induced a rapid (15 min) and transitory (90 min) corticosterone rise into the hippocampus dHPC, and a reversal of serial memory retrieval pattern; (ii) both the endocrinal and memory stress-induced effects were blocked by metyrapone; (iii) corticosterone-BSA injection into the dHPC in non stressed mice mimicked the effects of stress on serial retrieval pattern. Overall, our study is first to show that (i) a rapid stress-induced corticosterone rise into the dHPC transitorily reverses serial memory retrieval pattern and (ii) hippocampal corticosterone membrane receptors activation is involved in the rapid effects of acute stress on serial memory retrieval.


Subject(s)
Corticosterone/metabolism , Hippocampus/physiopathology , Mental Recall/physiology , Stress, Psychological/physiopathology , Analysis of Variance , Animals , Catheterization , Cattle , Corticosterone/blood , Discrimination, Psychological/drug effects , Discrimination, Psychological/physiology , Enzyme Inhibitors/pharmacology , Hippocampus/drug effects , Male , Mental Recall/drug effects , Metyrapone/pharmacology , Mice , Mice, Inbred BALB C , Microdialysis , Neuropsychological Tests , Serum Albumin, Bovine/metabolism , Stress, Psychological/blood , Stress, Psychological/drug therapy
3.
Neuroscience ; 162(4): 1351-65, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19490932

ABSTRACT

The mechanisms of epileptogenesis remain largely unknown and are probably diverse. The aim of this study was to investigate the role of focal cholinergic imbalance in epileptogenesis. To address this question, we monitored electroencephalogram (EEG) activity up to 12 weeks after the injection of a potent cholinesterase (ChE) inhibitor (soman) at different doses (0.53, 0.75, 1, 2, 2.8, 4 and 11 nmol) into the right dorsal hippocampus of C57BL/6 mice. Different parameters were used to choose the dose for a focal model of epileptogenesis (mainly electrographic patterns and peripheral ChE inhibition). The pattern of neuronal activation was studied by Fos immunohistochemistry (IHC). Brain damage was evaluated by hemalun-phloxin, neuronal nuclei antigen IHC and silver staining. Glial fibrillary acidic protein IHC was used to evaluate astroglial reaction. Finally, long-term behavioral consequences were characterized. At the highest dose (11 nmol), soman quickly evoked severe signs, including initial seizures and promoted epileptogenesis in the absence of tissue damage. With lower doses, late-onset seizures were evidenced, after 1-4 weeks depending on the dose, despite the absence of initial overt seizures and of brain damage. Only a weak astroglial reaction was observed. Following injection of 1 nmol, Fos changes were first evidenced in the ipsilateral hippocampus and then spread to extrahippocampal areas. A selective deficit in contextual fear conditioning was also evidenced two months after injection. Our data show that focal hypercholinergy may be a sufficient initial event to promote epilepsy and that major brain tissue changes (cellular damage, edema, neuroinflammation) are not necessary conditions.


Subject(s)
Acetylcholinesterase/metabolism , Cholinesterase Inhibitors , Epilepsy/enzymology , Hippocampus/enzymology , Soman , Animals , Astrocytes/pathology , Conditioning, Psychological , Dose-Response Relationship, Drug , Electroencephalography , Epilepsy/chemically induced , Epilepsy/pathology , Epilepsy/physiopathology , Fear , Genes, Immediate-Early , Hippocampus/pathology , Hippocampus/physiopathology , Male , Maze Learning , Mice , Mice, Inbred C57BL , Periodicity , Proto-Oncogene Proteins c-fos/biosynthesis , Proto-Oncogene Proteins c-fos/genetics , Rotarod Performance Test , Seizures/chemically induced , Seizures/enzymology , Seizures/pathology , Seizures/physiopathology , Time Factors
4.
Neurobiol Learn Mem ; 90(2): 395-403, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18572424

ABSTRACT

Previous data from our team have shown that pre-test stress in mice reversed the pattern of memory retrieval in a contextual serial spatial task (CSD; Celerier, A., Pierard, C., Rachbauer, D., Sarrieau, A., & Beracochea, D. (2004). Contextual and serial discriminations: A new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learning and Memory, 11, 196-204). The present study is aimed at determining brain areas which might be critically involved in mediating the stress effect on memory retrieval in the CSD task. For that purpose, we studied hereby the effects of ibotenic acid lesions of either the prefrontal cortex (PFC) or the basolateral amygdala (BLA) in Stressed or Non-Stressed Balb/c mice on memory retrieval in the CSD task. In that task, mice learned two successive spatial discriminations (D1 and D2) within two different internal contexts in a four-hole board. The stressor (electric footshocks) was delivered 5 min before test, occurring 24 h after acquisition. During test, mice were relocated either on the floor of the first or of the second discrimination. Results showed that (i) spatial memory was substantial and remained unaffected both by lesions and stress; (ii) Non-Stressed controls as well as Non-Stressed or Stressed PFC and BLA-lesioned mice remembered accurately D1 but not D2; and (iii) in contrast, Stressed controls accurately remembered D2 but not D1. In parallel to behavioral experiments, we also showed that PFC and BLA lesions did not affect the stress-induced increase of plasma corticosterone levels. All together, PFC and BLA integrity are not necessary for retrieval processes per se; in contrast, the PFC and BLA are critically involved in the mediation of the deleterious stress effects on serial order memory retrieval.


Subject(s)
Amygdala/physiology , Arousal/physiology , Mental Recall/physiology , Orientation/physiology , Prefrontal Cortex/physiology , Reversal Learning/physiology , Serial Learning/physiology , Animals , Appetitive Behavior/physiology , Attention/physiology , Brain Mapping , Corticosterone/blood , Cues , Discrimination Learning/physiology , Electroshock , Fear/physiology , Ibotenic Acid , Male , Mice , Mice, Inbred BALB C , Retention, Psychology/physiology
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