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Intracerebroventricular injection of streptozotocin causes neurotoxicity to myelin that contributes to spatial memory deficits in rats.

It has been reported that intracerebroventricular (icv) injection of streptozotocin (STZ) impairs spatial memory by disrupting glucose utilization through an insulin-dependent mechanism in the cerebral cortex and hippocampus. However, evidence of septal damage and microglosis induced by icv STZ suggested that its neurotoxic effects could contribute to the memory impairment. The present study examined the histopathological changes in adult rats following three icv STZ injections (0.25 mg into each lateral ventricle) and their effects on spatial memory in a Morris water maze task. STZ retarded acquisition of reference learning (progressive reduction in escape latency) and disrupted working memory (difference in escape latency between the two swims within a daily session). STZ caused selective injury to myelin and axons in the fornix and hippocampus in association with activation of microglia. The 3rd ventricle was enlarged by 100-150% because of a loss of ependymal cells and damage to hypothalamic periventricular myelin but the process involved in these changes is unclear. Our findings provide an alternative explanation for the decrease in glucose utilization in the hippocampus and cortex and the impairment of spatial memory induced by STZ. These could result from a disruption of the communication through myelinated axons in the fornix connecting the septum and the hippocampus, and through other myelinated axons adjacent to the ventricles. The selective damage to myelin may well result from oxidative stress.

Animals↗

Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation.

We investigated the effects of ovariectomy (OVX) and 17 beta-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (A beta) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the A beta-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to A beta-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of A beta or formation of amyloid plaques.

Age Factors↗

Experience-dependent regulation of zif268 gene expression and spatial learning.

Environmental enrichment (EE) is known to enhance the cognitive ability of rodents. To translate EE to the human condition, it is important to understand the parameters of its efficacy. In this study, we examine if the cognitive enhancement associated with EE is permanent and whether a developmental window exists for its efficacy. Rats were housed in continuous isolation (ISO), continuous enrichment (EE), enrichment from postnatal day (PN) 21-50, and then isolation from PN50-79 (PM), or isolation from PN21-50 and then enriched from PN50-79 (CW). Spatial learning ability and basal expression of the immediate-early genes zif268 and Arc as well as the NR1 subunit of the NMDA receptor were assessed. Rats housed in an enriched environment at the time of testing (EE and CW) performed significantly better in the spatial learning task than rats housed in an isolated environment at the time of testing (ISO and PM). Enhanced performance in the spatial learning task was associated with a higher expression of zif268 only in the CA3/CA4 region of the hippocampus. Our study further defines parameters that make environmental enrichment effective in enhancing learning performance and the findings may be helpful in the translation of this intervention to the human condition.

Animals↗

Bilateral injection of isoproterenol into hippocampus induces Alzheimer-like hyperphosphorylation of tau and spatial memory deficit in rat.

The abnormal hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer disease and other tauopathies; as yet the exact role of various tau kinases in this pathology is not fully understood. Here, we show that injection of isoproterenol, an activator of cAMP-dependent kinase (PKA), into rat hippocampus bilaterally results in the activation of PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibition of protein phosphatase-2A, hyperphosphorylation of tau at several Alzheimer-like epitopes and a disturbance of spatial memory retention 48 h after the drug injection. These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment.

Alzheimer Disease↗

Middle-old and old-old retirement dwelling adults respond differently to locomotor challenges in cluttered environments.

Obstacle navigation during locomotion was investigated in older adults using an obstacle course paradigm under different ambient lighting conditions. Similar strategies for obstacle navigation were observed between the two age groups studied (middle-old: 75-85 years and old-old adults: 85 years and older), however old-old individuals were "less" successful at avoiding obstacles. Differences observed between the two age groups in obstacle course performance may be attributed to changes in spatial reference frames that occur with age and/or differences in perceived threat of obstacles in the travel path. Reduced lighting conditions and increasing age were also found to have significant affects on obstacle navigation.

Accidental Falls↗

Control strategies used by older adults during multiple obstacle avoidance.

The purpose of our study was to determine the methods of control over the center of mass (COM) utilized by older adults when navigating a functional obstacle course. The course included three different types of obstacles placed closely in series requiring subjects to walk around, step over and duck under. Optoelectric cameras were used to record kinematic data as older adults navigated the course under normal and low lighting and different obstacle contrast conditions. Results were compared across lighting conditions and obstacle contrast conditions. Statistical analyses revealed that older adults are able to successfully navigate a functional obstacle course through increases in their trunk motion and a reduction in their average step velocity, via changes in step length or cadence. These adaptations may pose a challenge to the limits of stability of an older adult and place them at a greater risk of falling when avoiding obstacles in their travel path.

Adaptation, Physiological↗

Travel path conditions dictate the manner in which individuals avoid collisions.

The ability to perceive the motion of approaching objects and to make appropriate adjustments to avoid collisions is an essential component of safe locomotion through the environment. No previous study has looked at actual behavioural responses in a realistic collision avoidance task. We investigated individuals' collision avoidance behaviour with an approaching object in order to understand the visual information used to accomplish the task. We found that when individuals were walking towards a goal without any restrictions, a change in travel path occurred at the same time, independent of the object's approach velocity. However, the lateral rate of change in the travel path was significantly slower for the slower approach velocity. We found that when a restriction was present along the travel path, individuals were exposed to the object's properties for longer and a change in travel path occurred later for slowest approaching velocities than for the fastest approaching velocities. The results suggest that individuals are capable of determining TTC from an approaching object during actual self-motion, but the motor parameter it modulates is different for different circumstances.

Adult↗

Ecological analysis of the distribution and socio-spatial context of homicides in Porto Alegre, Brazil.

Over the last decade, the number of homicides in Porto Alegre has increased to the point where external causes are now the main group of causes of death in the 5-34-year age group. Preventing these deaths depends fundamentally on identifying factors related to excess violence in population groups. The overall aim of this study is to analyse the spatial distribution of homicide victims by place of residence in Porto Alegre, the capital of the southernmost Brazilian State of Rio Grande do Sul, in 1996, in order to identify and understand the socio-spatial context. Demographic and socioeconomic indicators based on the 1991 census and 1996 population count were used to build a multivariate classification characterizing the 1851 census tracts. Homicides occurring in 1996 were located using the municipality's Geographic Information System. Four socioeconomic groups were identified, mainly differentiated by housing indicators. Small areas on the urban periphery in which slums (favelas) are concentrated presented higher homicide rates. Homicide rates were lower in the two groups with higher income and educational level. The second step was to classify the census tracts according to the homicide indicator. In this case, areas were differentiated by the number of household inhabitants per room, income, schooling, and median age. We conclude that the multivariate socioeconomic classification presents a limited capacity to identify populations exposed to homicides, suggesting that socioeconomic conditions themselves do not determine violent behaviour. On the other hand, the spatial methods allowed us to identify small areas where deaths are concentrated and whose populations should receive special attention in planning measures to prevent violent deaths.

Adolescent↗

Horizontal and vertical effects of eye-position on sound localization.

The effect of gaze direction on the localization of sound sources was investigated in the azimuthal and elevational dimension using a pointing task. In both dimensions, eccentric eye-position induced a significant shift in sound localization that was opposite to the direction of eccentricity. This finding is in accordance with the view that the azimuthal and elevational components of the auditory spatial information are processed in common neural substrates.

Acoustic Stimulation↗

Kicking coordination captures differences between full-term and premature infants with white matter disorder.

This study explores the relation of white matter disorder (WMD) to intralimb coordination patterns in premature infants with very low birth weight (VLBW). We specifically measured the temporal-spatial characteristics of intralimb coordination patterns of the legs. Three groups of infants were compared at one month corrected age (CA): 10 premature infants born VLBW and WMD (PTWMD), 10 premature infants born VLBW without WMD (PT) and 10 full term infants (FT). Using kinematic variables, we discriminate among VLBW infants with WMD from the two comparison groups. Infants born with WMD maintain patterns of tight coupling among leg joints (all flexion or all extension) while PT and FT term infants have begun to decouple leg joints by this age (combinations of flexion with extension). The coupling pattern is captured through joint correlations, discrete relative phase, and phase plane portraits. The PTWMD infants also demonstrate aberrant patterns of coordination evident through both temporal and spatial characteristics of the kicks. This is the first evidence that movement disorder associated with brain lesions can be identified and quantified with kinematic variables as early as one month of age.

Brain↗

The effects of viscous loading of the human forearm flexors on the stability of coordination.

This experiment investigated whether the stability of rhythmic unimanual movements is primarily a function of perceptual/spatial orientation or neuro-mechanical in nature. Eight participants performed rhythmic flexion and extension movements of the left wrist for 30s at a frequency of 2.25 Hz paced by an auditory metronome. Each participant performed 8 flex-on-the-beat trials and 8 extend-on-the-beat trials in one of two load conditions, loaded and unload. In the loaded condition, a servo-controlled torque motor was used to apply a small viscous load that resisted the flexion phase of the movement only. Both the amplitude and frequency of the movement generated in the loaded and unloaded conditions were statistically equivalent. However, in the loaded condition movements in which participants were required to flex-on-the-beat became less stable (more variable) while extend-on-the-beat movements remained unchanged compared with the unload condition. The small alteration in required muscle force was sufficient to result in reliable changes in movement stability even a situation where the movement kinematics were identical. These findings support the notion that muscular constraints, independent of spatial dependencies, can be sufficiently strong to reliably influence coordination in a simple unimanual task.

Adult↗

Interaction of neuromuscular, spatial and visual constraints on hand-foot coordination dynamics.

In the present study, we investigated the contributions of motor and perceptual processes to directional constraints as observed during hand-foot coordination. Participants performed cyclical flexion-extension movements of the right hand and foot under two coordination modes: in-phase (isodirectional) and antiphase (non-isodirectional). Those tasks were performed either with full vision or no vision of the limbs. Depending on the position of the forearm (prone or supine), the coordination patterns were performed with similar and dissimilar neuro-muscular coupling with respect to their phylogenetic origin as antigravity muscles. Results showed that the antiphase pattern was more difficult to maintain than the in-phase pattern and that neuro-muscular coupling significantly influenced the coordination dynamics. Moreover, the effect of vision differed as a function of both neuro-muscular coupling and coordination mode. Under dissimilar neuro-muscular coupling, the presence of visual feedback stabilized the in-phase pattern and destabilized the antiphase pattern. In contrast, visual feedback did not influence pattern stability during conditions of similar neuro-muscular coupling. These results shed light on the complex interactions between motor and perceptual (visual) constraints during the production of hand-foot coordination patterns.

Adult↗

Advancing age progressively affects obstacle avoidance skills in the elderly.

The ability to adequately avoid obstacles while walking is an important skill that allows safe locomotion over uneven terrain. The high proportion of falls in the elderly that is associated to tripping over obstacles potentially illustrates an age-related deterioration of this locomotor skill. Some studies have compared young and old adults, but very little is known about the changes occurring within different age groups of elderly. In the present study, obstacle avoidance performance was studied in 25 young (20-37 years) and 99 older adults (65-88 years). The participants walked on a treadmill at a speed of 3 km/h. An obstacle was dropped 30 times in front of the left foot at various phases in the step cycle. Success rates (successful avoidance) were calculated and related to the time available between obstacle appearance and the estimated instant of foot contact with the obstacle (available response times or ARTs ranging from 200 to more than 350 ms). In addition, latencies of avoidance reactions, the choice of avoidance strategies (long or short step strategy, LSS or SSS), and three spatial parameters related to obstacle avoidance (toe distance, foot clearance, and heel distance) were determined for each participant. Compared to the young, the older adults had lower success rates, especially at short ARTs. Furthermore, they had longer reaction times, more LSS reactions, smaller toe and heel distances, and larger foot clearances. Within the group of elderly, only the 65-69 year olds were not different from young adults with respect to success rate, despite marked changes in the other parameters measured. In particular, even this younger group of elderly showed a dramatic reduction in the amount of SSS trials compared to young adults. Overall, age was a significant predictor of success rates, reaction times, and toe distances. These parameters deteriorated with advancing age. Finally, avoidance success rates at short ARTs were considerably worse in elderly participants who sustained recurrent falls in the six-month period prior to the assessment compared to those who sustained no or only one fall. An exercise program has been shown to improve avoidance success rates, especially at short ARTs, but the training effects on the determinants of success still need to be assessed.

Accidental Falls↗

Disorientation inhibits landmark use in 12-18-month-old infants.

Recent research has indicated that, particularly under conditions of inertial disorientation, mammals may be sensitive to landmark configuration geometry at the expense of individual featural information when locating hidden goals. The current study sought to establish whether landmark use could be demonstrated in 12-18-month-old infants with and without a disorientation procedure, and with geometrically ambiguous landmark configurations. A peekaboo paradigm was employed in which infants learned to anticipate a peekaboo event after a cue from two locations within a circular arena, followed by a test trial from a novel position in which no peekaboo occurred after the cue. In all conditions, an isosceles triangle arrangement of landmarks was used, with peekaboo occurring between the landmarks of one of the two equal "sides", thus being geometrically ambiguous. In two conditions, the landmarks were distinctive, and in two further conditions, they were identical. In one of the distinctive conditions and one of the identical landmark conditions, infants underwent a disorientation procedure in between training and test trials. Only oriented infants with distinctive landmarks were successful in test trials, thus suggesting that infants are able to use the individual features of landmarks to locate a goal, but can only do so if oriented.

Confusion↗

The third spatial dimension risk approach for individual risk and group risk in multiple use of space.

Buildings above roads and railways are examples of multiple use of space. Safety is one of the critical issues for such projects. Risk analyses can be undertaken to investigate what safety measures that are required to realise these projects. The results of these analyses can also be compared to risk acceptance criteria, if they are applicable. In The Netherlands, there are explicit criteria for acceptability of individual risk and societal risk. Traditionally calculations of individual risk result in contours of equal risk on a map and thus are considered in two-dimensional space only. However, when different functions are layered the third spatial dimension, height, becomes an important parameter. The various activities and structures above and below each other impose mutual risks. There are no explicit norms or policies about how to deal with the individual or group risk approach in the third dimension. This paper proposes an approach for these problems and gives some examples. Finally, the third dimension risk approach is applied in a case study of Bos en Lommer, Amsterdam.

Bayes Theorem↗

Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning abilities in mice.

The serotonin (5-hydroxytryptamine, 5-HT) receptor 1A is involved in many physiological functions, including the regulation of learning and memory by acting either as an autoreceptor located on 5-HT neurons (raphe nuclei) or as a heteroreceptor on non-5-HT neurons, mainly in the hippocampal formation. To investigate whether the effects of 5-HT via 5-HT1A receptors on learning are age-sensitive, we evaluated the performance of young-adult (3 months old) and aged (22 months old) 5-HT1A knockout (KO) mice and their homologous wild types (WT) in the hippocampal-dependent spatial reference memory version of the Morris water maze. We demonstrated that young-adult 5-HT1AKO mice exhibit an impairment in learning and retention of the spatial task, as compared to WT mice, without showing any sign of change in their sensori-motor and locomotor abilities or motivation. This genotype effect does not persist during aging. In fact, aged 5-HT1AKO mice seem to be slightly facilitated during the early stages of learning. These results are consistent with a possible prevalence of 5-HT1A raphe functions in learning and memory abilities of young-adult animals, since the effects of the mutation on mice performance (impairment) are opposite to those found after intra-raphe injection of 5-HT1A agonists (facilitation), and with data showing increased activity of 5-HT neurons in 5-HT1AKO mice. The reduced effect of the mutation in aged animals possibly reflects the lower efficacy of autoreceptors due to aging and/or a prevalence of hippocampal heteroreceptors.

Age Factors↗

Conditioned place preference associates with the mRNA expression of diazepam binding inhibitor in brain regions of the addicted rat during withdrawal.

The diazepam binding inhibitor (DBI) modulating the functions of the GABAA receptors is involved in the maladaptation of neural system during using opiate, but its role in opiate dependence is not fully understood. Using conditioned place preference (CPP) rat model and in situ hybridization technique, we examined the correlation between opiate dependence and the mRNA expression of DBI. We found that chronic morphine treatment enabled CPP and increased the DBI mRNA expression in crucial brain regions of addiction. Withdrawal for 3 days caused significant physical signs and further increased the DBI mRNA expression. Both the DBI mRNA and CPP expression remained significantly high but physical signs were at control level in the animals withdrawal for 6 days. Remarkably, the DBI mRNA expressions in the CA1 region of the hippocampus (CA1), ventral tagmental area (VTA), nucleus accumbens (NAc) and amygdala (AMG) were positively correlated to CPP during the periods from withdrawal for 3 days to withdrawal for 6 days. These findings suggest that DBI may play a role in both physical and psychological dependence of opiates.

Animals↗

Use of clinical space as an indicator of student nurse's professional development and changing need for support.

A current challenge in educating nurses of the future is to support them during periods of immersion into the realities of today's health care settings during clinical practice rotations. The professional development of nursing students is dependent on their ability to integrate what they learn in the classroom with the realities that confront them during their clinical experiences. The success of clinical practice as a learning experience is dependent upon comprehensive learning support that is a collaborative responsibility between the triad of educator, clinical practitioner and student. Educators and clinical practitioners who work with students during clinical practice rotations must have an ability to recognise, and understand, the organisational behaviour of student nurses, to act as a mentor and support agent. Undergraduate student nurses undertaking their first clinical practice experience participated in an ethnographic hermeneutic study that explored the ways clinical practice in a small rural community influenced the way they shaped their professional identity. A key concern of ethnography is the way participants use space thus the theme described in this paper presents the ways students traversed space within the clinical environment and discusses how this use of space is indicative of students' professional development.

Education, Nursing, Baccalaureate↗