Το περιβάλλον διαθέτει πλούτο παραγόντων, οι οποίοι επηρεάζουν με θετικό ή αρνητικό τρόπο την ανάπτυξη και τη λειτουργία των οργανισμών. Μεταξύ των μετάλλων, ο μόλυβδος (Pb) θεωρείται ο σημαντικότερος νευροτοξικός περιβαλλοντικός παράγοντας, με τις κυριότερες αρνητικές επιδράσεις του να αφορούν νεαρούς οργανισμούς ή οργανισμούς που βρίσκονται στα πρώτα στάδια ανάπτυξης. Το περιβάλλον, ωστόσο, διαθέτει και πολλούς παράγοντες οι οποίοι δύνανται να χρησιμοποιηθούν για τις ευεργετικές τους ιδιότητες. Τα τελευταία χρόνια το επιστημονικό ενδιαφέρον έχει στραφεί στην εξεύρεση φυτών και φυτικών συστατικών που θα μπορούσαν να δρουν ενάντια της νευροτοξικής δράσης των μετάλλων. Η ελληνική χλωρίδα είναι πλούσια σε κοινά και ενδημικά φυτά που διαθέτουν νευροπροστατευτικές ιδιότητες. Ο σκοπός της εργασίας ήταν η διερεύνηση της πιθανής συσσώρευσης του μολύβδου στον ολικό εγκέφαλο (-παρεγκεφαλίδα) ενήλικων μυών και της πιθανής επαγωγής νευροτοξικών δράσεων, εστιάζοντας στη διεργασία μνήμη/μάθηση και την ενεργότητα του ενζύμου ακετυλοχολινεστεράση, ύστερα από χορήγηση διαλύματος μολύβδου (500 ppm) για διάστημα 4 εβδομάδων. Επιπλέον, διερευνήθηκε η πολυφαινολική σύσταση και η πιθανή προστατευτική δράση ενάντια στο μέταλλο των αφεψημάτων δυο φυτών της ελληνικής χλωρίδας, του κοινού Rosmarinus officinalis (δενδρολίβανο) και του υπενδημικού Hypericum vesiculosum, ύστερα από χορήγηση των αφεψημάτων σε ενήλικους μύες, καθώς και μετά από συγχορήγησή τους με το μόλυβδο για χρονικό διάστημα 4 εβδομάδων. To Η. vesiculosum δεν έχει μελετηθεί ποτέ ξανά ως προς τη σύσταση και τις ιδιότητές του. Τα αποτελέσματά μας υποδεικνύουν ότι και τα δυο αφεψήματα έχουν πλούσιο πολυφαινολικό περιεχόμενο, και ιδιαιτέρως το H. vesiculosum που υπερισχύει του δενδρολίβανου. Επιπλέον, με τη χρήση δυο φασματομετρικών μεθόδων (Φασματομετρία Ατομικής Απορρόφησης/AAS, Φασματομετρία Μάζας με Πηγή Επαγωγικά Συζευγμένου Πλάσματος/ICP-MS) αποδείχτηκε ότι ο Pb συσσωρεύεται στον εγκέφαλο ενήλικων μυών και αυτή η συσσώρευση δεν επηρεάζεται σε σημαντικό βαθμό από την συγχορήγηση των δυο αφεψημάτων με το μέταλλο. Ακόμα, η μελέτη της μνήμης και της μάθησης με τη χρήση της δοκιμασίας της Παθητικής Αποφυγής και η μελέτη της ενεργότητας της AChE στον ολικό εγκέφαλο (-παρεγκεφαλίδα) και στην παρεγκεφαλίδα [SS (διαλυτό σε άλας) κλάσμα που περιέχει κυρίως την G1 ισομορφή της AChE και DS (διαλυτό σε απορρυπαντικό κλάσμα) που περιέχει κυρίως την G4 ισομορφή της AChE, η οποία είναι πολύ σημαντική για το νευρικό σύστημα] απέδειξε ότι (α) ο μόλυβδος ασκεί τις νευροτοξικές του επιδράσεις προκαλώντας γνωστικές βλάβες και δυσλειτουργία του χολινεργικού συστήματος. Η ελάττωση της ενεργότητας της AChE μπορεί να οφείλεται στην αποικοδόμηση των χολινεργικών νευρώνων του ιππόκαμπου και της παρεγκεφαλίδας. (β) Τα δυο αφεψήματα αναστέλλουν την AChE με το δενδρολίβανο να είναι πιο αποδοτικό ακολουθώντας ιστοειδική δράση. Η διαδικασία της μνήμης/μάθησης δε φάνηκε να επηρεάζεται από τα δυο αφεψήματα αν και το δενδρολίβανο έδειξε ένα θετικό αποτέλεσμα που δεν ήταν στατιστικά σημαντικό. (γ) Η συγχορήγηση καθενός από τα αφεψήματα με το διάλυμα του Pb προκάλεσε σημαντικές αλλαγές στην ενεργότητα της AChE (ειδικά στο DS κλάσμα) και το R. officinalis ήταν περισσότερο αποτελεσματικό από το H. vesiculosum. Ολοκληρώνοντας, η συγχορήγηση υποδεικνύει ότι και τα δυο αφεψήματα επηρέασαν με παρόμοιο θετικό τρόπο τη γνωστική λειτουργία σε σχέση με τη δυσλειτουργία που είχε προκαλέσει ο Pb. / There are many environmental factors that can affect positively or negatively both the development and the functions of organisms. Among heavy metals, lead (Pb) is considered to be the most neurotoxic environmental factor, which exerts its negative effects especially in young or developmental organisms. However, there are many environmentally-based factors that could be used for their beneficial properties. In recent years, scientists have turned their interest to the discovery of plants and phenols that could protect the neural system against the neurotoxic effects of heavy metals. Hellenic flora is very rich in common and endemic plants with possible neuroprotective properties. The aim of the present study was to investigate the possible accumulation of lead in adult mice brain and the induction of neurotoxic effects, with emphasis on learning/memory process and acetylcholinesterase (AChE) activity, after the consumption of a lead solution (500 ppm), for 4 weeks. Furthermore, we investigated the polyphenolic content and the possible neuroprotective effects of two beverages (2%w/v), one of the common Rosmarinus officinalis (rosemary) and one of the endemic Hypericum vesiculosum, against metal’s toxicity after consumption/coadministration of each beverage with the lead solution, for 4 weeks. H. vesiculosum has never been studied before for its phenolic content, nor for its biological actions. Our results showed that the two beverages are rich in polyphenols, with H. vesiculosum been richer than R. officinalis. Moreover, the use of two spectrometric methods (Atomic Absorption Spectrometry/AAS, Inductively Coupled Plasma-Mass Spectrometry/ICP-MS) indicated that lead accumulates in adult mice brain, which was not affected after its co-administration with each beverage. Furthermore, the study of cognitive function, as assessed by Passive Avoidance test and determination of AChE activity in whole mice brain and cerebellum, [SS (salt soluble) fraction which contains the G1 isoform of AChE; and DS (detergent soluble) fraction which contains the G4 isoform of AChE that is very important for the neural system], demonstrated that: (a) lead exerts its neurotoxic effects by causing learning and memory deficits and dysfunction of the cholinergic system. The decrease of AChE activity may be due to the degeneration of the cholinergic neurons in the hippocampus and cerebellum; (b) Both beverages inhibit AChE activity, with rosemary being more effective and tissue-specific, while no effect was observed on learning/memory, after consumption of the two beverages. Only rosemary showed a positive effect that wasn’t, however, statically important; (c) The co-administration of each beverage with the lead solution caused important changes in AChE activity (especially in the G4 isoform), and R. officinalis was more effective than H. vesiculosum. Both beverages showed similar protective effects against Pb-induced cognitive dysfunctions in mice.

Amyloid beta (ABeta) and tau protein are both implicated in memory impairment in early Alzheimer’s disease, but whether and how they interact to cause synaptic dysfunction are unknown. Consequently, I firstly investigated whether tau protein is required for the robust phenomenon of ABeta-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. I demonstrate that the absence of tau prevents the ABeta-induced impairment of LTP; moreover, a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks both an ABeta-induced increase in tau phosphorylation and the ABeta-induced LTP impairment. Thus, tau protein, likely in its phosphorylated form, is required for ABeta to impair LTP. Secondly, I investigated the underlying mechanisms for this ABeta-induced impairment and find that ABeta changes the balance between the two major types of glutamate receptors involved in plasticity processes, with a specific effect on GluN2B subunit-containing NMDA receptors. Since the distribution of these receptors is asymmetric between the left and right mouse hippocampus, I accessed these different types of synapses optogenetically and found that only the GluN2B-rich synapses receiving left CA3 input show ABeta-induced changes in the balance of glutamate receptors, suggesting an asymmetry in synaptic vulnerability to ABeta. Moreover, there was a left-right difference in tetanus-induced LTP and therefore, thirdly, I investigated whether mice have a hemispheric dissociation in memory processing using acute optogenetic silencing of left or right CA3 during hippocampus-dependent memory tasks. Unilateral silencing of either the left or the right CA3 caused a deficit in short-term memory, but only left CA3 silencing impaired performance on a spatial long-term memory task. Together, these results suggest that memory may be routed via distinct left-right pathways within the mouse hippocampus, and that neural pathways subserving distinct functions may also be differentially vulnerable to pathological changes at the synaptic level.

No description available.

Overexpression of the NR2B subunit of the NMDA receptor in the forebrain has been shown to improve learning and memory in mice (Tang et al 1999), which provides exciting implications for the enhancement of human cognition. However, it was first essential to establish replicability, and since the Tang et al (1999) study used only male mice we wished to investigate possible sex differences. On the hidden platform watermaze, we found a trend for male NR2BOE mice to learn the task more quickly than male wildtype mice (as observed by Tang et al. 1999), but the opposite trend in female mice; female NR2BOE mice were slower to reach the hidden platform than female wildtype mice. This pattern of results was also observed on the spatial reference Y memory task and open field task (for anxiety), although not on the spatial working memory T maze task (despite a sex difference). However, wildtype and NR2BOE mice performed at similar levels on the novel object recognition task, the spatial novelty preference task, visible platform watermaze and visual discrimination task. A battery of tests considering some species typical behaviours of mice demonstrated that wildtype and NR2BOE mice were comparable on tests of motor ability, strength, co-ordination, anxiety, burrowing and nesting. This suggests that our behavioural results are not due to a general impairment or enhancement of species typical behaviours. We considered the possibility that the difference between the results of Tang et al (1999) and those we observed may be caused by age differences; hence we attempted to replicate our results on the hidden platform watermaze, spatial reference Y maze and open field test in age matched mice. However, the second cohort of NR2BOE mice performed at similar levels to wildtype mice, and at significantly improved levels compared to the mice of the first cohort. We also considered the effects of knocking out the NR2B subunit on learning and memory, and NR1 subunit deletion within the hippocampus. On the spatial working memory T maze, these mouse strains performed similarly to their respective wildtype strains. Similarly, on a two beacon watermaze (with one indicating the platform position), mice lacking the NR2B subunit were able to locate the platform in a similar length of time. To ensure that the null results we had observed in the second cohort were not due to loss of the NR2B protein overexpression in the forebrain, we performed polymerase chain reactions (PCR), quantitative real-time PCR, and Western blots. We ascertained that the transgene was indeed present and that NR2B mRNA and protein levels were elevated in the hippocampi of the NR2BOE mice. In conclusion, it is unclear why the behaviours we observed in the NR2BOE mice are different to those published in the literature. It is possible that they may be due to differences in environmental enrichment, but the cause of the genotype by sex differences observed in the mice of cohort 1 is unclear. Nonetheless, we have advanced our knowledge of the effects of modifications in the levels of the NR2B subunit of the NMDA receptor on learning and behaviour.

In this thesis, Stroop task performance was investigated (using behavioural, electrophysiological and functional magnetic resonance imaging (fMRI) techniques) in late and proficient adult bilinguals currently living in the second language (L2) environment. Monolingual participants, matched for age and handedness, were recruited as controls. The Stroop colour-word task was considered an appropriate tool to test the general hypothesis that bilingualism might influence executive or cognitive control processes. In Study One, a dual-task paradigm was used for assessing the lateralisation of language functions (given the linguistic nature of the Stroop paradigm used here) in the bilinguals (Macedonian-English/M-E). Bilinguals showed a more bilateral hemispheric involvement, for both languages, compared to monolinguals. These findings also provided supporting evidence for the hypothesis of greater right-hemispheric involvement for language in bilinguals. In Study Two, two behavioural Stroop task paradigms (manual and verbal) were used in order to assess the magnitude of the Stroop effect between the groups. Bilinguals (M-E, German-English/G-E) showed a trend of smaller interference scores across both languages compared to monolinguals. In Study Three, manual Stroop task performance with concurrent electroencephalograph (EEG) recording revealed that bilinguals had temporal shifts in the N400 component (of about 30-40 ms) for the interference comparison for both languages compared to monolinguals. Also, relative to monolinguals, M-E bilinguals (for both L1 and L2) and G-E bilinguals (for L2) had fewer electrodes over frontal and central sites with a significant amplitude difference in the interference comparison (i.e., a reduced interference effect). In Study Four, the neural substrates engaged during Stroop task performance were investigated using fMRI. In general, monolinguals showed greater activation in regions such as the prefrontal cortex and anterior cingulate (regions associated with good executive control). This suggested that relative to bilinguals, monolinguals require more neural resources to accomplish conflict resolution. Taken together, Stroop task performance in late and proficient bilinguals currently living in the L2 environment differed from that of monolinguals across all methods of investigation. It appears that cognitive processing changes at the executive level can be observed as a result of bilingualism. The results also provide some evidence for changes in L1 processing following late L2 acquisition, as similar results across both languages and tasks were observed for the M-E bilinguals. It is also possible that slight modifications to cerebral laterality as a result of the late learning of (and continuous exposure to) a second language could contribute to these differences in executive functioning. The language environment might therefore be a major factor in the lateralisation of language processing and executive functioning in bilinguals. These conclusions, though tentative and require further investigation, have important implications for language and executive processing in general and for theories regarding cognitive flexibility in bilinguals. / Auckland University Doctoral Scholarship

In this thesis, Stroop task performance was investigated (using behavioural, electrophysiological and functional magnetic resonance imaging (fMRI) techniques) in late and proficient adult bilinguals currently living in the second language (L2) environment. Monolingual participants, matched for age and handedness, were recruited as controls. The Stroop colour-word task was considered an appropriate tool to test the general hypothesis that bilingualism might influence executive or cognitive control processes. In Study One, a dual-task paradigm was used for assessing the lateralisation of language functions (given the linguistic nature of the Stroop paradigm used here) in the bilinguals (Macedonian-English/M-E). Bilinguals showed a more bilateral hemispheric involvement, for both languages, compared to monolinguals. These findings also provided supporting evidence for the hypothesis of greater right-hemispheric involvement for language in bilinguals. In Study Two, two behavioural Stroop task paradigms (manual and verbal) were used in order to assess the magnitude of the Stroop effect between the groups. Bilinguals (M-E, German-English/G-E) showed a trend of smaller interference scores across both languages compared to monolinguals. In Study Three, manual Stroop task performance with concurrent electroencephalograph (EEG) recording revealed that bilinguals had temporal shifts in the N400 component (of about 30-40 ms) for the interference comparison for both languages compared to monolinguals. Also, relative to monolinguals, M-E bilinguals (for both L1 and L2) and G-E bilinguals (for L2) had fewer electrodes over frontal and central sites with a significant amplitude difference in the interference comparison (i.e., a reduced interference effect). In Study Four, the neural substrates engaged during Stroop task performance were investigated using fMRI. In general, monolinguals showed greater activation in regions such as the prefrontal cortex and anterior cingulate (regions associated with good executive control). This suggested that relative to bilinguals, monolinguals require more neural resources to accomplish conflict resolution. Taken together, Stroop task performance in late and proficient bilinguals currently living in the L2 environment differed from that of monolinguals across all methods of investigation. It appears that cognitive processing changes at the executive level can be observed as a result of bilingualism. The results also provide some evidence for changes in L1 processing following late L2 acquisition, as similar results across both languages and tasks were observed for the M-E bilinguals. It is also possible that slight modifications to cerebral laterality as a result of the late learning of (and continuous exposure to) a second language could contribute to these differences in executive functioning. The language environment might therefore be a major factor in the lateralisation of language processing and executive functioning in bilinguals. These conclusions, though tentative and require further investigation, have important implications for language and executive processing in general and for theories regarding cognitive flexibility in bilinguals. / Auckland University Doctoral Scholarship

In this thesis, Stroop task performance was investigated (using behavioural, electrophysiological and functional magnetic resonance imaging (fMRI) techniques) in late and proficient adult bilinguals currently living in the second language (L2) environment. Monolingual participants, matched for age and handedness, were recruited as controls. The Stroop colour-word task was considered an appropriate tool to test the general hypothesis that bilingualism might influence executive or cognitive control processes. In Study One, a dual-task paradigm was used for assessing the lateralisation of language functions (given the linguistic nature of the Stroop paradigm used here) in the bilinguals (Macedonian-English/M-E). Bilinguals showed a more bilateral hemispheric involvement, for both languages, compared to monolinguals. These findings also provided supporting evidence for the hypothesis of greater right-hemispheric involvement for language in bilinguals. In Study Two, two behavioural Stroop task paradigms (manual and verbal) were used in order to assess the magnitude of the Stroop effect between the groups. Bilinguals (M-E, German-English/G-E) showed a trend of smaller interference scores across both languages compared to monolinguals. In Study Three, manual Stroop task performance with concurrent electroencephalograph (EEG) recording revealed that bilinguals had temporal shifts in the N400 component (of about 30-40 ms) for the interference comparison for both languages compared to monolinguals. Also, relative to monolinguals, M-E bilinguals (for both L1 and L2) and G-E bilinguals (for L2) had fewer electrodes over frontal and central sites with a significant amplitude difference in the interference comparison (i.e., a reduced interference effect). In Study Four, the neural substrates engaged during Stroop task performance were investigated using fMRI. In general, monolinguals showed greater activation in regions such as the prefrontal cortex and anterior cingulate (regions associated with good executive control). This suggested that relative to bilinguals, monolinguals require more neural resources to accomplish conflict resolution. Taken together, Stroop task performance in late and proficient bilinguals currently living in the L2 environment differed from that of monolinguals across all methods of investigation. It appears that cognitive processing changes at the executive level can be observed as a result of bilingualism. The results also provide some evidence for changes in L1 processing following late L2 acquisition, as similar results across both languages and tasks were observed for the M-E bilinguals. It is also possible that slight modifications to cerebral laterality as a result of the late learning of (and continuous exposure to) a second language could contribute to these differences in executive functioning. The language environment might therefore be a major factor in the lateralisation of language processing and executive functioning in bilinguals. These conclusions, though tentative and require further investigation, have important implications for language and executive processing in general and for theories regarding cognitive flexibility in bilinguals. / Auckland University Doctoral Scholarship

In this thesis, Stroop task performance was investigated (using behavioural, electrophysiological and functional magnetic resonance imaging (fMRI) techniques) in late and proficient adult bilinguals currently living in the second language (L2) environment. Monolingual participants, matched for age and handedness, were recruited as controls. The Stroop colour-word task was considered an appropriate tool to test the general hypothesis that bilingualism might influence executive or cognitive control processes. In Study One, a dual-task paradigm was used for assessing the lateralisation of language functions (given the linguistic nature of the Stroop paradigm used here) in the bilinguals (Macedonian-English/M-E). Bilinguals showed a more bilateral hemispheric involvement, for both languages, compared to monolinguals. These findings also provided supporting evidence for the hypothesis of greater right-hemispheric involvement for language in bilinguals. In Study Two, two behavioural Stroop task paradigms (manual and verbal) were used in order to assess the magnitude of the Stroop effect between the groups. Bilinguals (M-E, German-English/G-E) showed a trend of smaller interference scores across both languages compared to monolinguals. In Study Three, manual Stroop task performance with concurrent electroencephalograph (EEG) recording revealed that bilinguals had temporal shifts in the N400 component (of about 30-40 ms) for the interference comparison for both languages compared to monolinguals. Also, relative to monolinguals, M-E bilinguals (for both L1 and L2) and G-E bilinguals (for L2) had fewer electrodes over frontal and central sites with a significant amplitude difference in the interference comparison (i.e., a reduced interference effect). In Study Four, the neural substrates engaged during Stroop task performance were investigated using fMRI. In general, monolinguals showed greater activation in regions such as the prefrontal cortex and anterior cingulate (regions associated with good executive control). This suggested that relative to bilinguals, monolinguals require more neural resources to accomplish conflict resolution. Taken together, Stroop task performance in late and proficient bilinguals currently living in the L2 environment differed from that of monolinguals across all methods of investigation. It appears that cognitive processing changes at the executive level can be observed as a result of bilingualism. The results also provide some evidence for changes in L1 processing following late L2 acquisition, as similar results across both languages and tasks were observed for the M-E bilinguals. It is also possible that slight modifications to cerebral laterality as a result of the late learning of (and continuous exposure to) a second language could contribute to these differences in executive functioning. The language environment might therefore be a major factor in the lateralisation of language processing and executive functioning in bilinguals. These conclusions, though tentative and require further investigation, have important implications for language and executive processing in general and for theories regarding cognitive flexibility in bilinguals. / Auckland University Doctoral Scholarship

Jan Raška: Reactions of the jumping spider Evarcha arcuata to aposematic true bugs Abstract: This paper studies the effect of qualities of a prey on predatory behaviour of Evarcha arcuata (Araneae: Salticidae). Naturally coloured aposematic larveae of Pyrrhocoris apterus have been compared to two types of prey: 1) to identically coloured but in defensive secretion different larvae of Scantius aegyptius, and 2) differently coloured larvae of white mutants of P. apterus. The defensive secretion of S. aegyptius has been found less effective in the first interaction with predator than that of P. apterus, however, after several trials the difference of reactions of the spider has not been noticeable. When changed the species of prey, E. arcuata has symmetrically and considerably generalised between the two species. Significant difference has been established in memory test - while P. apterus has been avoided even after one day, S. aegyptius has been attacked as thought the spiders were naive. The learning sequence has been similar in both colour forms of P. apterus; the generalisation of the two colours has been symetrical as well. Both colour forms succeeded in memory test (e.g. spiders have proven difference in comparison with the naive ones), however, white mutants have been successfully attacked...

Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) and δ-9-tetrahydrocannabinol (THC or ‘cannabis’). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.