Hexapeptides HLDF-6 and PEDF-6 restore memory in rats after chronic intracerebroventricular treatment with β-amyloid peptide Aβ(25–35)

Effects of homologous peptides HLDF-6 and PEDF-6 on behavior of animals with experimental Alzheimer’s disease induced by chronic intracerebroventricular administration of β-amyloid peptide Aβ(25–35) were studied in the zoosocial recognition test and Morris water maze. Peptides HLDF-6 and PEDF-6 possessed neuroprotective activity and counteracted the toxic effect of Aβ(25–35). Peptides HLDF-6 and PEDF-6 mainly improved long-term memory and working memory, respectively. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 3, pp. 292–296, March, 2006     

Spatial and Frequency Differences of Neuromagnetic Activities Between the Perception of Open- and Closed-class Words

The present study investigated the spatial and frequency differences of neuromagnetic activities between the perception of open- and closed-class words by using a 275-channel whole head magnetoencephalography (MEG) system. Two groups of words, 110 open-class and 110 closed-class, were presented visually and auditorily simultaneously. The data of 12 healthy subjects were analyzed with synthetic aperture magnetometry (SAM) which can identify the frequency-dependent volumetric distribution of evoked magnetic fields (EMFs). Both vocabulary classes elicited spectral power changes in the left inferior frontal gyrus (Broca’s area) and left posterior-superior temporal gyrus (Wernicke’s area) within 70–120 Hz. However, the open-class words elicited event-related desynchronization (ERD) while the closed-class words elicited event-related synchronization (ERS) in the two areas within 70–120 Hz. In addition, the open-class words also elicited ERS in the right inferior frontal gyrus, right middle frontal gyrus and right inferior parietal lobe within 1–8 Hz, but the closed-class words only elicited ERD in the right inferior frontal gyrus within 1–8 Hz. Furthermore, there were ERD in the right posterior-superior temporal gyrus within 120–200 Hz for the open-class words, but not for the closed-class words. These results indicate that open- and closed-class words are processed differently in the brain, not only in the anatomical substrates, but also in the frequency range of neuromagnetic activity.     

A new method for express analysis of flavonoid fraction in nephrophite plant extract and prediction of its antioxidant effects

A new chromatographic procedure is proposed for rapid (35 min) complete fractionation of flavonoids in plant raw material; the method well discriminates between components with antioxidant activity (rutin, apigenin, quercetin, hesperidin). The method is based on reverse-phase high performance liquid chromatography using ODS-S5CN carrier and linear 10–60% pyridine elution gradient. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 6, pp. 715–717, June, 2006     

Syntactic processing of auditory and visual sentences in a learning‐disabled child: Relation to short‐term memory

The nature of a short‐term memory deficit and its relation to syntactic processing were investigated in a learning‐disabled child. The child showed reduced short‐term memory span for both auditorily and visually presented lists. The short‐term memory deficit was attributed to a disruption of phonological storage on the basis of several lines of evidence: No phonological similarity effect was obtained for visual presentation, the recency effect was absent for auditory presentation, and memory was normal for item information but poor for order information. On several syntactic tests, the child showed normal performance for visual presentation but impaired performance for auditory presentation. The deficit for auditory presentation was most obvious for syntactically complex sentences. The child's normal performance for visual presentation suggests that phonological short‐term memory does not play a critical role in reading comprehension. For auditory presentation, we hypothesize that phonological short‐term memory serves to hold subsequent words in a sentence while the syntactic analysis of earlier parts is completed.     

Learning and memory: Traditional and systems approaches

The aims of the present work were to consider the characteristics of learning and memory from the point of view of a systems approach and to compare this view with the traditional approach. Neuron activity is regarded not as a response to the synaptic influx resulting in excitation but as a means of altering the cell’s relationship with its environment, whose “action” is to eliminate discordance between the cell’s “needs” and its microenvironment. The neuronal mechanisms of learning and consolidation of memory are regarded not as formation of a stable increase in the efficiency of synaptic transmission in circuits of connected neurons, but as a system genesis event which confers new system specializations on neurons which do not have to be directly connected synaptically. The roles of the processes of selection, reconsolidatory modification of previously formed memories, gene activation, neurogenesis, and apoptosis in systems genesis occurring both in normal and pathological conditions are discussed. Individual development is regarded as a sequence of system genesis events. The systems approach is applied to the phenomenon of long-term potentiation. In conclusion, a scheme including different types and stages of memory formation is presented. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 6, pp. 842–860, November–December, 2005. This article is based on a report presented to the Second Simonov Conference, April 20, 2004 (“Learning and memory: a systems perspective,” Second Simonov Conference, Russian Academy of Sciences Press, Moscow (2004), pp. 3–51).     

The role of the cognitive activity context in the conservatism of unconscious visual sets

Studiesin healthy adults were performed to compare measures of the rigidity of a verbal set in three series of experiments: in series 1, pseudowords were presented at the set-forming stage of the experiment, while common words were presented in the test stage; series 2 used the pseudoword/word conditions of series 1 with the additional task of identifying the position of a target stimulus in a matrix, requiring discrimination from other symbols in terms of two characteristics; in series 3, the pseudoword/word test was followed by an initial task consisting of identifying the matrix position of a target stimulus in conditions in which the need to discriminate was minimized. The results supported the hypothesis that the rigidity of a visual set depends on the cognitive activity context. This property is significantly dependent on the loading applied to working memory and the cognitive tasks solved by the subject, particularly the ratio of involvement of the ventral and dorsal visual systems in the cortical processing of sequentially acting verbal and non-verbal visual stimuli. The cognitive set paradigm serves as a model for experimental studies of the roles of the ventral and dorsal visual systems in organizing recognition functions. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 5, pp. 633–638, September–October, 2005.     

Spatial organization of cortical electrical activity at different stages of a visual set in preschool and early school age

Parameters of the formation of a visual nonverbal set and the rate of its replacement with a new set were compared in children of three age groups: 5–6, 6–7, and 9–10 years. The vast majority of subjects (27 of 30 preschool children and 42 of 43 third-grade children) showed clear set effects. Age-related differences in set plasticity and the dynamics of reaction times to test stimuli were observed. The set was more rigid in children aged 5–6 years than in older children. Differences in the dynamics of the spatial organization of alpha and theta activity were seen in the anterior areas of the cortex at different stages of the set in children of different age groups. Analysis of cortical potentials coherence functions and behavioral parameters led to the hypothesis that the frontothalamic selective attention system and the corticohippocampal connection system responsible for the cortical processing of new visual information and episodic memory function are involved in organizing the visual set. A critical age (from six to seven years) was indentified in the formation of plastic types of visual nonverbal sets. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 58, No. 1, pp. 46–55, January–February, 2008.     

Effects of β-amyloid (25–35) on learning in the common snail

The effects of neurotoxic β-amyloid fragment (25–35) on the formation of behavioral sensitization and a conditioned defensive reflex to food were studied. Administration of β-amyloid (25–35) to common snails before the start of training led to a significant reduction in sensitization of the defensive reaction, weakening of the formation of the conditioned defensive reflex to food, and impairment of memory. These impairments to behavioral plasticity may be mediated by changes in synaptic plasticity previously observed in the presence of β-amyloid. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 57, No. 2, pp. 229–236, March–April, 2007.     

Central Administration of Amyloid β-Peptide (25–35) and Individual Features of Cognitive Behavior in Rats

The individual characteristics of cognitive behavior induced by intracerebroventricular administration of aggregated amyloid β-peptide (25–35) (Aβ_25–35) were studied. A new approach to evaluating individual features of the actions of Aβ_25–35 was used. Navigational training was performed in a single brief session using random target positions, and training sessions were repeated a few days later. These experiments produced the first indication that cognitive behavior was undamaged in 50% of the rats at the early stage of Aβ_25–35 exposure. The activities of the antioxidant enzymes superoxide dismutase and catalase in the cortex and hippocampus were significantly decreased in animals with and without cognitive impairments. We suggest that phenotypic characteristics may underlie the individual features of the animals’ responses to Aβ. At the early stage, aggregated Aβ may induce a compensatory reaction which prevents impairment of cognitive processes.     

Biochemical markers of apoptosis in different parts of the brain during learning

Caspase-3 activity and the levels of DNA fragments of 200–600 and >4000 b.p. were estimated in the cerebellar vermis, the hippocampus, and the prefrontal cortex of the brains of adult rats four and 24 months after training to extinction of the acoustic startle reaction and conditioned fear. Differently timed changes in the levels of biochemical markers of apoptosis were seen to different extents in these brain areas after training. These changes were characterized by a decrease in caspase-3 activity in the cerebellar vermis and the hippocampus, with decreases in DNA fragmentation in the hippocampus and cerebral cortex and increases in measures of programmed cell death in the hypothalamus. These experimental data support the view that the apoptosis of cells in the mature brain is involved in the mechanisms of learning and memory. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 6, pp. 729–733 November–December, 2005.     

Central injection of caspase inhibitors facilitates the formation of freezing behavior in rats

We studied the effects of central administration of pancaspase inhibitor z-VAD-fmk and specific caspase 3 inhibitor z-DEVD-fmk on learning and memory in rats. The inhibitors selectively facilitated the formation of freezing behavior without modulating consolidation and retrieval of passive defense behavior in the model of conditioned freezing. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 497–500, May, 2007     

Cortical gamma activity during auditory tone omission provides evidence for the involvement of oscillatory activity in top-down processing

Perception is an active process in which our brains use top-down influences to modulate afferent information. To determine whether this modulation might be based on oscillatory activity, we asked seven subjects to detect a silence that appeared randomly in a rhythmic auditory sequence, counting the number of omissions (“count” task), or responding to each omission with a right index finger extension (“move” task). Despite the absence of physical stimuli, these tasks induced a ‘non-phase-locked’ gamma oscillation in temporal–parietal areas, providing evidence of intrinsically generated oscillatory activity during top-down processing. This oscillation is probably related to the local neural activation that takes place during the process of stimulus detection, involving the functional comparison between the tones and the absence of stimuli as well as the auditory echoic memory processes. The amplitude of the gamma oscillations was reduced with the repetition of the tasks. Moreover, it correlated positively with the number of correctly detected omissions and negatively with the reaction time. These findings indicate that these oscillations, like others described, may be modulated by attentional processes. In summary, our findings support the active and adaptive concept of brain function that has emerged over recent years, suggesting that the match of sensory information with memory contents generates gamma oscillations.     

Advancing age alters the influence of eye position on sound localization

Vision and audition provide spatial information about the environment to guide natural behavior. Because the eyes move in the head while the ears remain head-fixed, input conveying eye position in the head is required to maintain audiovisual congruence. Human perception of auditory space was previously shown to shift with changes in eye position, regardless of the target’s frequency content and spatial cues underlying horizontal and vertical localization. In this study, we examined whether this interaction is altered by advancing age. Head-restrained young (18–44 yo), middle-aged (45–64 yo), and elderly (65–81 yo) human subjects localized noise bursts under conditions of transient and sustained ocular deflection. All three age groups demonstrated a time-dependent shift of auditory space in the direction of eye position. Moreover, this adaptation showed a clear decline with advancing age, but only for peripheral auditory space (beyond ±10° from midline). Alternatively, adaptation in the periphery may occur, but is more sluggish than in the central field and therefore not fully observed in this experiment. The age-dependent effect cannot be readily explained by senescent peripheral hearing loss, suggesting a change in central processing of auditory space in relation to the control of gaze.     

Magnified visual feedback exacerbates positional variability in older adults due to altered modulation of the primary agonist muscle

The purpose of this study was to determine whether magnified visual feedback during position-holding contractions exacerbates the age-associated differences in motor output variability due to changes in the neural activation of the agonist muscle in the upper and lower limb. Twelve young (18–35 years) and ten older adults (65–85 years) were instructed to accurately match a target position at 5° of index finger abduction and ankle dorsiflexion while lifting 10 % of their 1 repetition maximum (1RM) load. Position was maintained at three different visual angles (0.1°, 1°, and 4°) that varied across trials. Each trial lasted 25 s and visual feedback of position was removed from 15 to 25 s. Positional error was quantified as the root mean square error (RMSE) of the subject’s performance from the target. Positional variability was quantified as the standard deviation of the position data. The neural activation of the first dorsal interosseus and tibialis anterior was measured with surface electromyography (EMG). Older adults were less accurate compared with young adults and the RMSE decreased significantly with an increase in visual gain. As expected, and independent of limb, older adults exhibited significantly greater positional variability compared with young adults that was exacerbated with magnification of visual feedback (1° and 4°). This increase in variability at the highest magnification of visual feedback was predicted by a decrease in power from 12 to 30 Hz of the agonist EMG signal. These findings demonstrate that motor control in older adults is impaired by magnified visual feedback during positional tasks.     

Studies of the Effects of Central Administration of β-Amyloid Peptide (25–35): Pathomorphological Changes in the Hippocampus and Impairment of Spatial Memory

The possible link between amnesia induced by central administration of β-amyloid (25–35) (Aβ(25–35)) and neurodegenerative changes in the hippocampus was studied. Male Wistar rats received single intracerebroventricular injections of Aβ(25–35) at a dose of 15 nmoles and one month later were trained in an eight-arm radial maze. Training was followed by histological assessment of the state of the hippocampus on brain sections stained with hematoxylin and eosin. Aβ(25–35) induced impairments in long-term (reference) and working memory on testing in the maze. There was a moderate reduction in the number of neurons in hippocampal field CA1; there was no change in the number of cells in field CA3. The numbers of errors made by the animals on testing in the maze were found to correlate negatively with the numbers of nerve cells in hippocampal field CA1. Thus, this is the first demonstration that impairments of learning and memory induced by single doses of Aβ(25–35) are specifically associated with neurodegenerative changes in hippocampal field CA1 in rats. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 5, pp. 705–711, September–October, 2004.     

Rapid motor responses quickly integrate visuospatial task constraints

We have recently shown that subjects can appropriately modulate their rapid motor responses (traditionally termed reflexes) to move their hand to a spatial target when the target is displayed ~2 s before a mechanical perturbation (Pruszynski et al. in J Neurophysiol 100:224–238, 2008). The goal of this study was to investigate how quickly visual information can be used to modulate rapid motor responses to an impending mechanical perturbation. Following a 2 s to 10 ms target preview delay (PD), a perturbation either displaced the subject’s hand into or out of the previewed target. We also included a condition, where the target appeared after perturbation onset (target PD = +90 ms). In all cases, subjects were instructed to react as quickly as possible to the perturbation by reaching into the displayed target. Our results indicate that subjects began to incorporate visual information into their rapid motor responses with PDs as small as 70 ms. Interestingly, subjects reacted faster when the target was presented ~150 ms before the perturbation than when they had 2 s to prepare a response. Using receiver operative characteristic (ROC) analysis, we examined modulation of muscle activity as a function of preview delay in three predefined epochs. No modulation was found in the short-latency epoch (R1; 20–45 ms). In contrast, both the long-latency (45–105 ms) and voluntary (120–180 ms) epochs were modulated at essentially the same time, 140 ms from visual presentation of the target to the beginning of each respective epoch.     

Formation of Spatial Memory in Rats with Ischemic Lesions to the Prefrontal Cortex; Effects of a Synthetic Analog of ACTH(4-7)

Photochemically induced thrombosis of blood vessels in the prefrontal cortex in rats was shown to lead to ischemic infarcts in the lesion zone. Bilateral ischemic lesioning of the prefrontal cortex degraded measures of spatial memory when animals were tested in a Morris water maze with an invisible platform 20–24 days after surgery. Chronic intranasal administration of the peptide Met-Glu-His-Phe-Pro-Gly-Pro (Semax), a synthetic analog of ACTH(4-7), at a dose of 250 μg/kg/day during the first six days after photothrombosis, led to recovery of the animals’ learning ability. The long-term antiamnestic action of the peptide observed here may result from its neuroprotective activity and its ability to stimulate the synthesis of neurotrophic factors.     

Changes in Cell Proliferation in the Subventricular Zone of the Brain in Adult Rats Given β-Amyloid Peptide (25–35)

The effects of intracerebroventricular administration of fragment (25–35) of β-amyloid peptide [Aβ(25–35)] on cell proliferation in the subventricular zone of the dentate gyrus of the hippocampus in adult rats were analyzed. Animals received doses of 15 nmol of pre-aggregated Aβ(25–35) or the Aβ(35–25) control peptide, or solvent (sterile water) into the lateral ventricles. On post-injection days 1–5, rats received intraperitoneal injections of the thymidine analog 5-bromo-2’-deoxyuridine (BrdU). BrdU incorporated into DNA was detected immunohistochemically on frontal brain sections six and 12 days after peptide administration. At six days, the numbers of BrdU-containing cells in the subventricular zone showed no differences between the study groups. At 12 days, the total number of BrdU-positive cells decreased significantly in all study groups. At the same time, the number of labeled cells in rats given Aβ(25–35) was significantly greater in this brain zone than in animals given water or the control peptide. Thus, Aβ(25–35) significantly increased cell proliferation in the subventricular zone after intracerebroventricular administration.     

Effects of partial intraspecies deprivation of rats on short-term image memory

An individual’s zoosocial experience plays a significant role in the formation of adaptive behavior in animals. Published data show that significant restriction of intraspecies interactions induces impairments of higher nervous activity, including such functions as learning, memory, and the control of emotions. These changes are particularly marked when deprivation of zoosocial interactions occurs in the early stage of the animal’s postnatal development. We have previously demonstrated that psychogenic stress in rats reared from an early age (from 14 days after birth) in conditions of visual and tactile deprivation leads to impairment of long-term (conditioned reflex) memory functions, this being accompanied by significant suppression of self-regulatory brain activity. The aim of the present work was to investigate the effects of partial intraspecies deprivation in early ontogenesis on overall behavior and short-term memory in adult rats. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 3, pp. 368–370, May–June, 2005.     

Use of Noben (idebenone) in the Treatment of Dementia and Memory Impairments without Dementia

Noben (idebenone) at a dose of 120 mg per day for six months was used in the treatment of 35 patients aged 60–86 years with Alzheimer’s-type dementia, mixed dementia, and memory impairments not reaching the stage of dementia. Patients were assessed on the basis of data from somatic, neurological, and psychiatric investigations, as well as neuropsychological testing and a series of psychometric and other scales and tests, before and after treatment. Significant improvements in patients’ conditions on the MMSE were seen in patients with mild and moderate dementia. Improvements in daily activities were obtained in 27% of patients. Neuropsychological investigations demonstrated improvements in short-term and long-term memory and attention, with improvements in speech functions, performance of kinesthetic, spatial, and dynamic praxis tests, and in visuospatial gnosis, thought, and writing. On the CGI scale, positive treatment effects were obtained in 37% of patients, while 48% of patients remained in a stable state. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 108, No. 4, pp. 27–32, April, 2008.