Long lasting effects of early-life stress on glutamatergic/GABAergic circuitry in the rat hippocampus

Martišová, Eva; Solas, Maite; Horrillo, I.; Ortega, Jorge E.; Meana, J. Javier; Tordera, Rosa M.; Ramı́rez, Marı́a J.

doi:10.1016/j.neuropharm.2011.12.019

Cited by 103 publications

(69 citation statements)

References 44 publications

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“…However, after CFC with memantine treatment levels of GLUR4 (but neither pGLUR2 nor GLUR3) were elevated in the membrane compared with NL. GLUR4 levels normally are highest in early postnatal times, but increases have been documented in several rodent model systems, in responses to stress, ischemia and environmental enrichment (97)(98)(99). Lastly, memantine uniquely caused apparent degradation of NR2A with a significant decrease in cytosolic levels.…”

Section: Discussionmentioning

confidence: 99%

Protein Profiles Associated With Context Fear Conditioning and Their Modulation by Memantine

Ahmed

Dhanasekaran

Block

et al. 2014

Molecular & Cellular Proteomics

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Analysis of the molecular basis of learning and memory has revealed details of the roles played by many genes and the proteins they encode. Because most individual studies focus on a small number of proteins, many complexities of the relationships among proteins and their dynamic responses to stimulation are not known. We have used the technique of reverse phase protein arrays (RPPA) to assess the levels of more than 80 proteins/ protein modifications in subcellular fractions from hippocampus and cortex of mice trained in Context Fear Conditioning (CFC). Proteins include components of signaling pathways, several encoded by immediate early genes or involved in apoptosis and inflammation, and subunits of glutamate receptors. At one hour after training, levels of more than half the proteins had changed in one or more fractions, among them multiple components of the Mitogen-activated protein kinase, MAPK, and Mechanistic Target of Rapamycin, MTOR, pathways, subunits of glutamate receptors, and the NOTCH pathway modulator, NUMB homolog (Drosophila). Levels of 37 proteins changed in the nuclear fraction of hippocampus alone. Abnormalities in levels of thirteen proteins analyzed have been reported in brains of patients with Alzheimer's Disease. We therefore further investigated the protein profiles of mice treated with memantine, a drug approved for treatment of AD. In hippocampus, memantine alone induced many changes similar to those seen after CFC and altered the levels of seven proteins associated with Alzheimer's Disease abnormalities. Lastly, to further explore the relevance of these datasets, we superimposed responses to CFC and memantine onto components of the long term potentiation pathway, a process subserving learning and memory formation. Fourteen components of the long term potentiation pathway and 26 proteins interacting with components responded to CFC and/or memantine. Together, these datasets provide a novel view of the diversity and complexity in protein responses and interactions following normal learning. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Protein Profiles Associated With Context Fear Conditioning and Their Modulation by Memantine

Ahmed

Dhanasekaran

Block

et al. 2014

Molecular & Cellular Proteomics

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“…administration of ACPT-I reduced immobility time in the rat FST (Tatarczyñska et al, 2002;Pałucha et al, 2004), the effect being blocked by a group III mGlu antagonist, CPPG [(RS)-a-cyclopropyl-4-phosphonophenylglycine]. Furthermore, enhanced depression-like immobility in the FST, as the outcome of the maternal separation procedure in the rat, has upregulated mGlu 4 receptor protein levels in the hippocampus, whereas chronic treatment with the antidepressant drug, serotonin-norepinephrine reuptake inhibitor venlafaxine, normalized immobility times and mGlu 4 receptor levels (Martisova et al, 2012). However, ACPT-I administered i.p.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 ADX88178 in Rodent Models of Neuropsychiatric Disorders

Kalinichev

Poul

Boléa

et al. 2014

J Pharmacol Exp Ther

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There is growing evidence that activation of metabotropic glutamate receptor 4 (mGlu 4 ) leads to anxiolytic-and antipsychotic-like efficacy in rodent models, yet its relevance to depression-like reactivity remains unclear. Here, we present the pharmacological evaluation of ADX88178 [5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine], a novel potent, selective, and brain-penetrant positive allosteric modulator of the mGlu 4 receptor in rodent models of anxiety, obsessive compulsive disorder (OCD), fear, depression, and psychosis. ADX88178 dose-dependently reduced the number of buried marbles in the marble burying test and increased open-arm exploration in the elevated plus maze (EPM) test, indicative of anxiolyticlike efficacy. Target specificity of the effect in the EPM test was confirmed using male and female mGlu 4 receptor knockout mice. In mice, ADX88178 reduced the likelihood of conditioned freezing in the acquisition phase of the fear conditioning test, yet had no carryover effect in the expression phase. Also, ADX88178 dose-dependently reduced duration of immobility in the forced swim test, indicative of antidepressantlike efficacy. ADX88178 reduced DOI (2,5-dimethoxy-4-iodoamphetamine)-mediated head twitches (albeit with no dose-dependency), and MK-801 [(5S,10R)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine]-induced locomotor hyperactivity in mice, but was inactive in the conditioned avoidance response test in rats. The compound showed good specificity as it had no effect on locomotor activity in mice and rats at efficacious doses. Thus, allosteric activation of mGlu 4 receptors can be a promising new therapeutic approach for treatment of anxiety, OCD, fear-related disorders, and psychosis.

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“…Prenatal infections and stress also increase depression-like behavior in adult rodents (Abe et al, 2007;Enayati et al, 2012;Lin and Wang, 2014;Tamura et al, 2011). During the early postnatal period, maternal separation, a commonly used experimental early-life stress, leads to increased anxiety-, depression-, and schizophrenialike behavior in adulthood Ellenbroek et al, 1998;Huot et al, 2001;Martisova et al, 2012;Romeo et al, 2003). In addition, juvenile rodents exposed to stressful events after weaning show increased depressionand anxiety-like behavior in adulthood (Jacobson-Pick and Richter-Levin, 2010;Pohl et al, 2007;Wilkin et al, 2012).…”

Section: Effects Of Early-life Experiences On Adult Neurogenesis and mentioning

confidence: 99%

Adult Neurogenesis and Mental Illness

Schoenfeld

Cameron

2014

Neuropsychopharmacol

155

108

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Several lines of evidence suggest that adult neurogenesis, the production of new neurons in adulthood, may play a role in psychiatric disorders, including depression, anxiety, and schizophrenia. Medications and other treatments for mental disorders often promote the proliferation of new neurons; the time course for maturation and integration of new neurons in circuitry parallels the delayed efficacy of psychiatric therapies; adverse and beneficial experiences similarly affect development of mental illness and neurogenesis; and ablation of new neurons in adulthood alters the behavioral impact of drugs in animal models. At present, the links between adult neurogenesis and depression seem stronger than those suggesting a relationship between new neurons and anxiety or schizophrenia. Yet, even in the case of depression there is currently no direct evidence for a causative role. This article reviews the data relating adult neurogenesis to mental illness and discusses where research needs to head in the future.

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Long lasting effects of early-life stress on glutamatergic/GABAergic circuitry in the rat hippocampus

Cited by 103 publications

References 44 publications

Protein Profiles Associated With Context Fear Conditioning and Their Modulation by Memantine

Protein Profiles Associated With Context Fear Conditioning and Their Modulation by Memantine

Characterization of the Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 ADX88178 in Rodent Models of Neuropsychiatric Disorders

Adult Neurogenesis and Mental Illness

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