Retraction notice to "Intensified mitochondrial hydrogen peroxide release occurs in all brain regions, affects male as well as female Rett mice, and constitutes a life-long burden" [Arch. Biochem. Biophys. 696 (15 December 2020) 10866].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and Authors. Professor Michael Müller approached the journal explaining that he had encountered an issue in the way the spectrofluorometric data analyses was performed. The normalization of the fluorescence curves to their respective starting points (as explained in Figure 1A) overestimated the changes in Mecp2-mutant mice, which usually started at lower levels. This overestimation applies to Figure 3 A-D as well as Table 2 and Table 3 and altered the outcomes of the study. Both the EiC and the authors agreed that a corrigendum would not be appropriate due to the change in conclusion and that the paper should therefore be retracted. The authors apologise for any confusion this paper may have resulted in.

Bioremediation potential of hexavalent chromium-resistant Arthrobacter globiformis 151B: study of the uptake of cesium and other alkali ions.

Cesium (Cs+) enters environments largely because of global release into the environment from weapons testing and accidents such as Fukushima Daiichi and Chernobyl nuclear waste. Even at low concentrations, Cs+ is highly toxic to ecological receptors because of its physicochemical similarity to macronutrient potassium (K+). We investigated the uptake and accumulation of Cs+ by Arthrobacter globiformis strain 151B in reference to three similar alkali metal cations rubidium (Rb+), sodium (Na+), and potassium (K+). The impact of hexavalent chromium (Cr+6) as a co-contaminant was also evaluated. A. globiformis 151B accumulated Cs+ and Cr6+ in a time-dependent fashion. In contrast, the uptake and accumulation of Rb+ did not exhibit any trends. An exposure to Cs+, Rb+, and Cr+6 triggered a drastic increase in K+ and Na+ uptake by the bacterial cells. That was followed by the efflux of K+ and Na+, suggesting a Cs+ "substitution." Two-dimensional gel-electrophoresis of bacterial cell proteomes with the following mass-spectrometry of differentially expressed bands revealed that incubation of bacterial cells with Cs+ induced changes in the expression of proteins involved in the maintenance of cellular homeostasis and reactive oxygen species removal. The ability of A. globiformis 151B to mediate the uptake and accumulation of cesium and hexavalent chromium suggests that it possesses wide-range bioremediation potential.

Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment.

The hippocampus, which provides cognitive functions, has been shown to become highly vulnerable during aging. One important modulator of the hippocampal neural network is the medial septum (MS). The present study attempts to determine how age-related mnemonic dysfunction is associated with neurochemical changes in the septohippocampal (SH) system, using behavioral and immunochemical experiments performed on young-adult, middle-aged and aged rats. According to these behavioral results, the aged and around 52.8% of middle-aged rats (within the "middle-aged-impaired" sub-group) showed both impaired spatial reference memory in the Morris water maze and habituation in the open field. Immunohistochemical studies revealed a significant decrease in the number of MS choline acetyltransferase immunoreactive cells in the aged and all middle-aged rats, in comparison to the young; however the number of gamma-aminobutyric acid-ergic (GABAergic) parvalbumin immunoreactive cells was higher in middle-aged-impaired and older rats compared to young and middle-aged-unimpaired rats. Western Blot analysis moreover showed a decrease in the level of expression of cholinergic, GABAergic and glutamatergic receptors in the hippocampus of middle-aged-impaired and aged rats in contrast to middle-aged-unimpaired and young rats. The present results demonstrate for the first time that a decrease in the expression level of hippocampal receptors in naturally aged rats with impaired cognitive abilities occurs in parallel with an increase in the number of GABAergic neurons in the MS, and it highlights the particular importance of inhibitory signaling in the SH network for memory function.

Galactose specific lectins from prostate tissue with different pathologies: biochemical and cellular studies.

BACKGROUND: Galectins-galactose-specific lectins are involved in various types of cell activities, including apoptosis, cell cycle regulation, inflammation and cell transformation. Galectins are implicated in prostate malignat transformation. It is not known yet if prostate glands with different grade of pathologies are expressing different galectins and if these galectins express different effects on the cell viability. METHODS: Cytosolic galactose-spesific lectin fractions from prostate tissue with different diagnosis were purified by affinity chromatography and analyzed by electrophoresis in polyacrylamide gel electrophoresis with sodium dodecyl sulphate. The lectin effects in a source-dependent maner were studied on cell viability on peripheral lymphocytes by MTT reduction method and on apoptosis by flow cytometry method. RESULTS: Affinity purified galactose-specific lectins fractions from normal and pathological tissue samples are characterized with different protein composition and they express different effects on cell viability and apoptosis. CONCLUSION: The effects of cytosolic galactose-specific lectins depend on the source of lectin fraction (glandular tissue disease). We suppose that the released cytosolic galectins from prostatic high grade intraepithelial neoplasia and adenocarcinoma tissue could suppress the immune status of the host patients.

Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats.

Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound-myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.

RETRACTED: Intensified mitochondrial hydrogen peroxide release occurs in all brain regions, affects male as well as female Rett mice, and constitutes a life-long burden.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and Authors. Professor Michael Müller approached the journal explaining that he had encountered an issue in the way the spectrofluorometric data analyses was performed. The normalization of the fluorescence curves to their respective starting points (as explained in Figure 1A) overestimated the changes in Mecp2-mutant mice, which usually started at lower levels. This overestimation applies to Figure 3 A-D as well as Table 2 and Table 3 and altered the outcomes of the study. Both the EiC and the authors agreed that a corrigendum would not be appropriate due to the change in conclusion and that the paper should therefore be retracted. The authors apologise for any confusion this paper may have resulted in.

Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons.

The medial septum (MS) is an important modulator of hippocampal function. The degree of damage in which the particular set of septo-hippocampal projections contributes to the deficits of spatial memory with concomitant changes of hippocampal receptors expression has not been studied till present. Therefore, we investigated spatial memory and the expression level of cholinergic (α7 nACh and M1), GABAergic (α1 subunit of GABAA) and glutamatergic (NR2B subunit of NMDA and GluR 1 subunit of AMPA) receptors in the hippocampus following selective lesions of cholinergic and GABAergic septo-hippocampal projection. Learning process and long-term spatial memory were assessed using a Morris water maze. The obtained results revealed that in contrast to cholinergic lesions, rats with MS GABAergic lesions exhibit a retention deficit in 3 days after training. Western blot analyses revealed the MS cholinergic lesions have significant effect on the expression level of the M1 mACh receptors, while MS GABAergic lesions induce dramatic modulations of hippocampal glutamatergic, cholinergic and GABAergic receptors expression. These results for the first time demonstrated that selective lesions of MS cholinergic and GABAergic neurons differentially affect long-term spatial memory and the memory deficit after MS GABAergic lesion is paralleled with significant changes of hippocampal glutamate, GABA and acetylcholine receptors expression.

Src-NADH dehydrogenase subunit 2 complex and recognition memory of imprinting in domestic chicks.

Src is a non-receptor tyrosine kinase participating in a range of neuronal processes, including synaptic plasticity. We have recently shown that the amounts of total Src and its two phosphorylated forms, at tyrosine-416 (activated) and tyrosine-527 (inhibited), undergoes time-dependent, region-specific learning-related changes in the domestic chick forebrain after visual imprinting. These changes occur in the intermediate medial mesopallium (IMM), a site of memory formation for visual imprinting, but not the posterior pole of the nidopallium (PPN), a control brain region not involved in imprinting. Src interacts with mitochondrial genome-coded NADH dehydrogenase subunit 2 (NADH2), a component of mitochondrial respiratory complex I. This interaction occurs at brain excitatory synapses bearing NMDA glutamate receptors. The involvement of Src-NADH2 complexes in learning and memory is not yet explored. We show for the first time that, independently of changes in total Src or total NADH2, NADH2 bound to Src immunoprecipitated from the P2 plasma membrane-mitochondrial fraction: (i) is increased in a learning-related manner in the left IMM 1 h after the end of training; (ii), is decreased in the right IMM in a learning-related way 24 h after training. These changes occurred in the IMM but not the PPN. They are attributable to learning occurring during training rather than a predisposition to learn. Learning-related changes in Src-bound NADH2 are thus time- and region-dependent.

Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies.

Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions. Methods: TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined. Results: For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated. Conclusion: TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation.

Myo-inositol treatment and GABA-A receptor subunit changes after kainate-induced status epilepticus.

Identification of compounds preventing the biochemical changes that underlie the epileptogenesis process is of great importance. We have previously shown that myo-Inositol (MI) daily treatment prevents certain biochemical changes that are triggered by kainic acid (KA)-induced status epilepticus (SE). The aim of the current work was to study the further influence of MI treatment on the biochemical changes of epileptogenesis and focus on changes in the hippocampus and neocortex of rats for the following GABA-A receptor subunits: α1, α4, γ2, and δ. After SE, one group of rats was treated with saline, while the second group was treated with MI. Control groups that were not treated by the convulsant received either saline or MI administration. 28-30 h after the experiment, a decrease in the amount of the α1 subunit was revealed in the hippocampus and MI had no significant influence on it. On the 28th day of the experiment, the amount of α1 was increased in both the KA- and KA + MI-treated groups. The α4 and γ2 subunits were strongly reduced in the hippocampus of KA-treated animals, but MI significantly halted this reduction. The effects of MI on α4 and γ2 subunit changes were significantly different between hippocampus and neocortex. On the twenty-eighth day after SE, a decrease in the amount of α1 was found in the neocortex, but MI treatment had no effect on it. The obtained results indicate that MI treatment interferes with some of the biochemical processes of epileptogenesis.

The protective effect of myo-inositol on hippocamal cell loss and structural alterations in neurons and synapses triggered by kainic acid-induced status epilepticus.

It is known that myo-inositol pretreatment attenuates the seizure severity and several biochemical changes provoked by experimentally induced status epilepticus. However, it remains unidentified whether such properties of myo-inositol influence the structure of epileptic brain. In the present light and electron microscopic research we elucidate if pretreatment with myo-inositol has positive effect on hippocampal cell loss, and cell and synapses damage provoked by kainic acid-induced status epilepticus. Adult male Wistar rats were treated with (i) saline, (ii) saline + kainic acid, (iii) myo-inositol + kainic acid. Assessment of cell loss at 2, 14, and 30 days after treatment demonstrate cytoprotective effect of myo-inositol in CA1 and CA3 areas. It was strongly expressed in pyramidal layer of CA1, radial and oriental layers of CA3 and in less degree-in other layers of both fields. Ultrastructural alterations were described in CA1, 14 days after treatment. The structure of neurons, synapses, and porosomes are well preserved in the rats pretreated with myo-inositol in comparing with rats treated with only kainic acid.

AMPA receptor phosphorylation and recognition memory: learning-related, time-dependent changes in the chick brain following filial imprinting.

There is strong evidence that a restricted part of the chick forebrain, the intermediate medial mesopallium (IMM), stores information acquired through the learning process of visual imprinting. We have previously demonstrated that at 1 h but not 24 h after imprinting training, a learning-specific increase in the amount of membrane Thr286-autophosphorylated α-calcium/calmodulin-dependent protein kinase II (αCaMKII), and in the proportion of total αCaMKII that is phosphorylated, occurs in the IMM but not in a control brain region, the posterior pole of the nidopallium (PPN). αCaMKII directly phosphorylates Ser831 in the GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. In the present study we have inquired whether the learning-related increase in αCaMKII autophosphorylation is followed by changes in the Ser831 phosphorylation of GluA1 (P-GluA1) and in the total amount of this subunit (T-GluA1). Trained chicks together with untrained control chicks were killed either 1 or 24 h after training. Tissue was removed from the IMM together with tissue from the PPN as a control. Amounts of P-GluA1 and T-GluA1 were measured. In the left IMM of the 1 h group the P-GluA1/T-GluA1 ratio increased in a learning-specific way. No learning-related changes were observed in other brain regions at 1 h or in any region 24 h after training. The results indicate that a time- and regionally-dependent, learning-specific increase in GluA1 phosphorylation occurs early in recognition memory formation.

Mitochondrial Proteome Changes in Rett Syndrome.

Rett syndrome (RTT) is a genetic neurodevelopmental disorder with mutations in the X-chromosomal MECP2 (methyl-CpG-binding protein 2) gene. Most patients are young girls. For 7-18 months after birth, they hardly present any symptoms; later they develop mental problems, a lack of communication, irregular sleep and breathing, motor dysfunction, hand stereotypies, and seizures. The complex pathology involves mitochondrial structure and function. Mecp2-/y hippocampal astrocytes show increased mitochondrial contents. Neurons and glia suffer from oxidative stress, a lack of ATP, and increased hypoxia vulnerability. This spectrum of changes demands comprehensive molecular studies of mitochondria to further define their pathogenic role in RTT. Therefore, we applied a comparative proteomic approach for the first time to study the entity of mitochondrial proteins in a mouse model of RTT. In the neocortex and hippocampus of symptomatic male mice, two-dimensional gel electrophoresis and subsequent mass-spectrometry identified various differentially expressed mitochondrial proteins, including components of respiratory chain complexes I and III and the ATP-synthase FoF1 complex. The NADH-ubiquinone oxidoreductase 75 kDa subunit, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, NADH dehydrogenase [ubiquinone] flavoprotein 2, cytochrome b-c1 complex subunit 1, and ATP synthase subunit d are upregulated either in the hippocampus alone or both the hippocampus and neocortex of Mecp2-/y mice. Furthermore, the regulatory mitochondrial proteins mitofusin-1, HSP60, and 14-3-3 protein theta are decreased in the Mecp2-/y neocortex. The expressional changes identified provide further details of the altered mitochondrial function and morphology in RTT. They emphasize brain-region-specific alterations of the mitochondrial proteome and support the notion of a metabolic component of this devastating disorder.

Filial imprinting in domestic chicks; cytoplasmic polyadenylation element binding protein 3, predispositions and learning.

Visual imprinting is a learning process, whereby young animals come to prefer a visual stimulus after exposure to it (training). Available evidence indicates that the intermediate medial mesopallium (IMM) in the domestic chick forebrain is a site of memory formation during visual imprinting. We have found previously that cytoplasmic polyadenylation element binding protein 3 in the P2 plasma membrane-mitochondrial fraction (CPEB3-P2) is upregulated in a learning-dependent way in the left IMM 24 h after training. CPEB3 has two forms, soluble and aggregated. Soluble CPEB3 represses translation; the aggregated form (CPEB3-AF) is amyloid-like and can promote translation. Our previous study did not show which of these two forms is increased after imprinting. We have now resolved this matter by measuring, 24 h after training, CPEB3-P2 and CPEB3-AF in the IMM and a control brain region, the posterior pole of nidopallium (PPN). The methods include imprinting training with a visual stimulus, behavioral measurement of preference, preparation of aggregated CPEB3, western immunoblotting, quantitation of proteins, statistical linear modeling. Only in the left IMM were the level of CPEB3-AF and learning strength correlated, increased CPEB3-AF level reflecting a predisposition to learn readily. CPEB3-P2 level also increased with learning strength in the left IMM, but as a result of learning. No correlations were detected in the right IMM or PPN. We propose two separate systems, both modulating synaptic strength through control of local translation. They are represented by CPEB3-AF (associated with a predisposition to learn) and soluble CPEB3 (associated with learning itself).

Metabolomic Fingerprint of Mecp2-Deficient Mouse Cortex: Evidence for a Pronounced Multi-Facetted Metabolic Component in Rett Syndrome.

Using unsupervised metabolomics, we defined the complex metabolic conditions in the cortex of a mouse model of Rett syndrome (RTT). RTT, which represents a cause of mental and cognitive disabilities in females, results in profound cognitive impairment with autistic features, motor disabilities, seizures, gastrointestinal problems, and cardiorespiratory irregularities. Typical RTT originates from mutations in the X-chromosomal methyl-CpG-binding-protein-2 (Mecp2) gene, which encodes a transcriptional modulator. It then causes a deregulation of several target genes and metabolic alterations in the nervous system and peripheral organs. We identified 101 significantly deregulated metabolites in the Mecp2-deficient cortex of adult male mice; 68 were increased and 33 were decreased compared to wildtypes. Pathway analysis identified 31 mostly upregulated metabolic pathways, in particular carbohydrate and amino acid metabolism, key metabolic mitochondrial/extramitochondrial pathways, and lipid metabolism. In contrast, neurotransmitter-signaling is dampened. This metabolic fingerprint of the Mecp2-deficient cortex of severely symptomatic mice provides further mechanistic insights into the complex RTT pathogenesis. The deregulated pathways that were identified-in particular the markedly affected amino acid and carbohydrate metabolism-confirm a complex and multifaceted metabolic component in RTT, which in turn signifies putative therapeutic targets. Furthermore, the deregulated key metabolites provide a choice of potential biomarkers for a more detailed rating of disease severity and disease progression.

Src and Memory: A Study of Filial Imprinting and Predispositions in the Domestic Chick.

Visual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The available evidence indicates that the intermediate medial mesopallium (IMM) in the domestic chick forebrain is a site of memory formation during visual imprinting. We have studied the role of Src, an important non-receptor tyrosine kinase, in memory formation. Amounts of total Src (Total-Src) and its two phosphorylated forms, tyrosine-416 (activated, 416P-Src) and tyrosine-527 (inhibited, 527P-Src), were measured 1 and 24 h after training in the IMM and in a control brain region, the posterior pole of nidopallium (PPN). One hour after training, in the left IMM, we observed a positive correlation between the amount of 527P-Src and learning strength that was attributable to learning, and there was also a positive correlation between 416P-Src and learning strength that was attributable to a predisposition to learn readily. Twenty-four hours after training, the amount of Total-Src increased with learning strength in both the left and right IMM, and amount of 527P-Src increased with learning strength only in the left IMM; both correlations were attributable to learning. A further, negative, correlation between learning strength and 416P-Src/Total-Src in the left IMM reflected a predisposition to learn. No learning-related changes were found in the PPN control region. We suggest that there are two pools of Src; one of them in an active state and reflecting a predisposition to learn, and the second one in an inhibited condition, which increases as a result of learning. These two pools may represent two or more signaling pathways, namely, one pathway downstream of Src activated by tyrosine-416 phosphorylation and another upstream of Src, keeping the enzyme in an inactivated state via phosphorylation of tyrosine-527.

Modulation of prefrontal cortex function by basal forebrain cholinergic and GABAergic neurons at the behavioral and molecular level.

The present research aimed to study the effects of selective immunolesions of cholinergic or gamma-aminobutyric acid (GABA)ergic neurons in the nucleus basalis magnocellularis (NBM) on memory function as well as cholinergic activity and the level of expression of glutamatergic [NR2B subunit of N-methyl-D-aspartate(NMDA)] receptors in the medial prefrontal cortex (mPFC) and hippocampus of behaviorally characterized rats. In behavioral experiments, working memory was assessed by a spatial alternation testing procedure in a plus-maze, and acquisition and retention of spatial memory was evaluated in a Morris water maze. The rats were divided into three groups: the NBM cholinergic, GABAergic immunolesioned groups and the normal control group. Cholin acetyltransferase or parvalbumin staining of the NBM and acetylcholinesterase staining of the mPFC and hippocampal sections were performed to visualize the effects of immunotoxins. The electrophoresis and immunoblotting were run to evaluate the effect of NBM lesions on the amount of the NR2B subunit of NMDA receptors. The results indicate that the immunolesion of cholinergic NBM neurons impair spatial working memory, as well as long-term spatial memory which is accompanied by significant changes in glutamatergic (the NR2B subunit of NMDA receptor) and cholinergic markers in the mPFC, whereas immunolesion of GABAergic NBM neurons does not affect long-term spatial memory, it does though cause the impairment of working memory with a reduction of the NMDA NR2B receptor signaling in the mPFC. The present results demonstrate that the cholinergic and GABAergic NBM cell groups play diverse and complementary roles and are integrated in distinct NBM-mPFC networks that may play different roles in mPFC memory function.

Influence of beta-galactose-specific mitochondrial lectins from prostate hyperplasic tissue on mitochondrial properties.

Galactose-specific lectins (Gal-lectins) were isolated from the mitochondrial fraction of prostate post-operational hyperplasic tissue of two diagnoses: benign prostate hyperplasic tissue with low-grade intraepithelial neoplasia (LGPIN) and benign prostate hyperplasic tissue with atypical adenomatous hyperplasia (AAH). They had similar molecular weight and other properties. Effects of these lectins were investigated in vitro model experiments on bovine liver cells mitochondrial properties. Time-dependent changes: (i) in the amount of H(2)O(2); (ii) redox state of Cu in cytochrome oxidase and (iii) redox state of heme in cytochrome a+a(3) (cyt a+a(3)) of cytochrome c oxidase complex were studied. Gal-lectins from both sources increase the amount of H(2)O(2) and decrease the redox state of Cu in cytochrome oxidase and heme in cyt a+a(3). However the Gal-lectin from tissue with more severed transformation (AAH) expresses significantly more strong and long-lasting influence. These effects are mediated by galactose binding domain of the lectins as are completely abolished by the inclusion of galactose in reaction medium. Accumulation of H(2)O(2) and long-lasting decrease in the redox state of key enzymes of mitochondrial respiration chain could induce defective functioning of these organelles and whole cells. Obtained data point the possible way, which enhances further transformation of prostate tissue by release of Gal-lectins from damaged mitochondria.

Chicken cognin interactome and the memory of filial imprinting.

Visual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The intermediate medial mesopallium in the domestic chick forebrain is critical for visual imprinting and contributes to molecular regulation of memory formation. Criteria used to infer that a change following training is learning-related have been formulated and published. Cognin (protein disulphide isomerase) is one of several identified plasma membrane and mitochondrial proteins that are upregulated in a learning-related way 24 hours after training. Since virtually nothing is known about the cognin interactome, we have used immunoaffinity chromatography and mass spectrometry to identify proteins that interact with cognin in the cytoplasmic and plasma membrane-mitochondrial fractions. As the learning-related upregulation of cognin has been shown to occur in the plasma membrane-mitochondrial fraction and not in the cytoplasmic fraction, we studied the effect of training on three cognin-interacting partners in the plasma membrane-mitochondrial fraction: the b5 subunit of mitochondrial ATP synthase and the alpha-2 and alpha-3 subunits of sodium-potassium ATPase. Learning-related upregulation was found in the left intermediate medial mesopallium 24 hours after training for the b5 subunit of mitochondrial ATP synthase and the alpha-2 subunit of sodium-potassium ATPase. The hemispheric asymmetry revealed here is consistent with the predominance of many other learning-related effects in the left intermediate medial mesopallium. The alpha-2 subunit of sodium-potassium ATPase is mainly expressed in astrocytes, supporting a role for these glial cells in memory.

Memantine treatment prevents okadaic acid induced neurotoxicity at the systemic and molecular levels.

The present study was designed to investigate the effects of okadaic acid intracerebroventricular (ICV) injection on memory function and expression level of α7 subunit of nicotinic acetylcholine receptor (nAChR) and NR2B subunit of NMDA glutamate receptors in the hippocampus, as well as effect of the antidementic drug memantine on okadaic acid induced changes at systemic and molecular levels in rats. Okadaic acid was dissolved in artificial cerebrospinal fluid (aCSF) and injected ICV 200 ng/10 µl. Vehicle control received 10 µl of aCSF ICV bilaterally. Control and okadaic acid injected rats were divided into two subgroups: treated i.p. with saline or memantine (5 mg/kg daily for 13 days starting from the day of okadaic acid injection). Rats were trained in the dual-solution plus-maze task that can be solved by using place or response strategies. The Western immunoblotting was used to determine relative amount of hippocampal receptors protein levels. Obtained data revealed that okadaic acid ICV injected rats were severely impaired at acquiring the place version of the maze accompanied by significant decline in hippocampal α7 subunit of nACh receptors protein levels. Memantine treatment can prevent okadaic acid induced impairment of hippocampal-dependent spatial memory and accompanied by modulation of the expression level of α7 subunit of nACh and NR2B subunit of NMDA receptors in the hippocampus. Thus, our results support the presumption that α7 nACh receptors may play an important role in the cognitive enhancer effects of memantine and emphasize the role of cholinergic-glutamatergic interactions in memory.