Transgenic mice expressing Alzheimer amyloid precursor proteins

Nearly a decade after the identification of the Alzheimer amyloid precursor protein (APP) gene several groups of investigators have created transgenic mice expressing APP that simulate some of the prominent behavioral and pathological features of Alzheimer's disease (Quon et al., 1991; Games et al., 1995; Hsiao et al., 1995, 1996; Moechars et al., 1996; Sturchler-Pierrat et al., 1997). These features, which are present to various degrees in different lines of mice, include age-related impairment in learning and memory, neuronal loss, gliosis, neuritic changes, amyloid deposition, and abnormal tau phosphorylation. No mouse model exhibiting every neuropathological feature of Alzheimer's disease exists. Whether an exact simulation of Alzheimer neuropathology is required to understand neural dysfunction in Alzheimer's disease is unclear. Various mouse models of Alzheimer's disease are summarized in this article.     

Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze.

The apolipoprotein E receptor 2 (ApoER2), expressed predominantly in forebrain regions including the hippocampus, is 1 of 2 receptors for the extracellular matrix protein reelin, which is critical for cortical development. Previous studies of ApoER2 mutant mice have indicated deficits in synaptic plasticity and learning. The current authors assessed learning and memory of ApoER2 knockout and wild-type mice on the Barnes circular maze. Mice were trained in this task for 22 days, followed by memory recall and reversal tests. ApoER2 knockout mice were initially slower to complete the task, but by Day 22 they were more accurate than wild-type mice on several indices. There were no differences in memory assessed by the recall task, but ApoER2 knockout mice performed significantly worse on the memory reversal task. ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparing prefrontal gray and white matter contributions to intelligence and decision making in schizophrenia and healthy controls.

The authors examined the relationship between neuropsychological performance and MRI of the orbital frontal cortex (OFC) and diffusion tensor imaging (DTI) of the cingulum bundle (CB) within groups of patients with schizophrenia and healthy subjects. The authors analyzed data from subjects, who had participated in prior MRI, DTI, and neuropsychological studies (Nakamura et al., 2008; Nestor et al., 2008). In comparison to healthy subjects, patients showed the expected reductions across CB fractional anisotropy (white matter) and OFC gray matter volume as well as lower neuropsychological scores. In addition, in comparison to healthy subjects, patients showed a very different pattern of functional-anatomical correlates. For patients, CB white matter but not OFC gray matter correlated with various aspects of intelligence, including general abilities and working memory. For controls, OFC gray matter but not CB white matter correlated with scores on tests of intelligence and decision making. These results point to the potentially important role of CB white matter in the neuropsychological disturbance in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Rats with complete cytotoxic hippocampal lesions exhibited spatial memory impairments in both the water maze and elevated T maze. They were hyperactive in photocell cages; swam faster in the water maze; and were less efficient on a nonspatial, differential reinforcement of low rates (DRL) task. Performance on both spatial tasks was also impaired by selective dorsal but not ventral lesions; swim speed was increased by ventral but not dorsal lesions. Both partial lesions caused a comparable reduction in DRL efficiency, although these effects were smaller than those of complete lesions. Neither partial lesion induced hyperactivity when rats were tested in photocell cages, although both complete and ventral lesion groups showed increased activity after footshock in other studies (Richmond et al., see record 1999-01985-006). These results demonstrate possible functional dissociations along the septotemporal axis of the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characteristics of age-related behavioral changes in senescence-accelerated mouse SAMP8 and SAMP10

Senescence-Accelerated Mouse (SAM), a murine model of accelerated senescence, has been established by Takeda et al. (1981). SAM consists of senescence-accelerated-prone mouse (SAMP) and senescence-accelerated-resistant mouse (SAMR), the latter of which shows normal aging characteristics. In 1991 there were eight different substrains in the P-series, which commonly exhibited accelerated aging with a shortened life span (Takeda et al., 1991). Among the P-series, we have found that SAMP8 mice show significant impairments in a variety of learning tasks when compared with SAMR1 mice (Miyamoto et al., 1986). Further studies suggest that SAMP8 exhibits an age-related emotional disorder characterized by reduced anxiety-like behavior (Miyamoto et al., 1992). On the other hand, it has been shown that SAMP10 exhibits brain atrophy and learning impairments in an avoidance task (Shimada et al., 1992, 1993). Here, characteristics of age-related deficits in learning and memory, changes in emotional behavior, and abnormality of circadian rhythms in SAMP8 and SAMP10 mice are described. In the experiments, SAMP8/Ta (SAMP8), SAMP10/(/)Ta (SAMP10) and SAMR1TA (SAMR1) reared under specific pathogen-free conditions at Takeda Chemical Industries were used.     

Single enrichment variables differentially reduce age-related memory decline in female mice.

The authors sought to determine how different elements of enrichment, for example, cognitive stimulation and voluntary exercise, differ in their ability to improve memory throughout the lifespan. Young, middle-aged, and aged female C57BL/6 mice received 24-hr exposure in their home cages to toys alone (cognitive stimulation), running wheels alone (exercise), or both toys and running wheels (complex enrichment) for 4 weeks prior to and then throughout spatial water maze testing. As expected, spatial memory became progressively worse with age. Exercise alone improved spatial water maze performance in young mice, whereas both exercise alone and complex enrichment improved spatial maze performance in middle-aged mice. All enrichment treatments improved spatial maze performance in aged mice. These data suggest that exercise is the most effective element of enrichment in young female mice and that both cognitive stimulation and exercise are necessary to reliably improve spatial water maze performance in aging female mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preserved pattern completion priming for novel, abstract geometric shapes in amnesics of several aetiologies

Two experiments were conducted using a paradigm developed by Gabrieli et al., Neuropsychologia 28, 417-427, 1990, which assessed both indirect and direct memory performance in a completion task for novel abstract geometric patterns. The preferred method of scoring was the lines method, based on the number of correct and incorrect lines produced for each item. It was chosen because it is both the simplest and the most informative measure. Two methods of scoring were used in previous work, namely, the strict whole figure method and the lenient whole figure method (Gabrielli et al., 1990; Verfaelie et al., Brain Cognit. 18, 34-45, 1992). Therefore to facilitate comparisons between studies and to determine the characteristics of different scoring methods, results with all three measures were included. In Experiment 1, two different encoding strategies of naming and copying were used in order to explore the relationship between indirect and direct memory performance. Indirect memory performance in the naming condition was at baseline whereas in the copying condition it was significantly above baseline. Cued recall did not differ across encoding conditions but recognition was higher in the naming condition than the copying condition. In Experiment 2, an attempt was made to extend the findings of two studies, one with H.M. (Gabrielli et al., 1990) and one with nine Korsakoffs (Verfaelie et al., 1992), to a larger group of 14 amnesics of several aetiologies. Indirect memory performance was found to be equivalent for the amnesics and their matched controls, only when the lenient and the lines methods of scoring were used. Recognition and cued recall performance was impaired for the amnesics compared to the controls.     

Construct validity of material-specific memory measures following unilateral temporal lobe ablations.

Material-specific memory test performance of 18 left (LTL), and 11 right (RTL), unilateral temporal lobectomy patients was assessed pre- and 1 wk postsurgery. The Selective Reminding Test (H. Buschke and P. A. Fuld; see record 1975-07695-001) and the Serial Digit Learning Test (A. L. Benton et al, 1983) were the verbal, and the Complex Figure Test and the Form Sequence Learning Test (K. Hamster et al, 1983) were the nonverbal, learning measures. Following surgery, LTLs showed significant reductions on both verbal memory tests, but no significant decline was observed in RTLs on the nonverbal memory measures' summary scores. Results suggest that Selective Reminding and Serial Digit Learning tests are sensitive to left temporal lesions but that Complex Figure and Form Sequence Learning tests, and by extension other nonverbal learning tests, should be interpreted cautiously with respect to unilateral temporal lobe dysfunction. Reasons for the difficulty in finding "pure" measures of visual learning are discussed, and suggestions for future nonverbal memory test development are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of Alzheimer's type dementia among dementias of the elderly]

In the authors experience of a memory clinic, about 2/3 of the patients fulfilled the criteria for dementia and among the demented patients 2/3 had probable Alzheimer's disease. Vascular dementia is the second cause of dementia in elderly people, but two other degenerative disorders fulfilling the NINCDS-ADRDA criteria for Alzheimer disease (Mc Khann et al., 1984) account for degenerative dementia. There is now a consensus for the clinical diagnosis and the neuropathological aspects of these two diseases: Dementia with Lewy Bodies (Mc Keith et al., 1996) and fronto-temporal dementia (the Lund and Manchester groups, 1994). The authors emphasize the clinical aspects of those two diseases at an early stage in comparison with dementia of Alzheimer type.     

Does auditory streaming require attention? Evidence from attentional selectivity in short-term memory.

R. P. Carlyon, R. Cusack, J. M. Foxton, and I. H. Robertson (2001; see record 2001-16068-008) have argued that attention is crucial for auditory streaming. The authors review R. P. Carlyon et al.'s (2001) arguments and suggest that a pertinent literature, the irrelevant sound paradigm--demonstrating preattentive auditory streaming--has been overlooked. In illustration of this alternative approach, the authors include a novel single experiment demonstrating the impact of preattentive auditory streaming on short-term serial memory. It is concluded that R. P. Carlyon et al.'s (2001) results do not definitively demonstrate that auditory streaming processes are dependent on attention; indeed, they are compatible with alternative accounts of the relationship between perceptual organization and attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pro region C-terminus:protease active site interactions are critical in catalyzing the folding of alpha-lytic protease

alpha-Lytic protease is encoded with a large (166 amino acid) N-terminal pro region that is required transiently both in vivo and in vitro for the correct folding of the protease domain [Silen, J. L. , and Agard, D. A. (1989) Nature 341, 462-464; Baker, D., et al. (1992) Nature 356, 263-265]. The pro region also acts as a potent inhibitor of the mature enzyme [Baker, D., et al. (1992) Proteins: Struct.,Funct., Genet. 12, 339-344]. This inhibition is mediated through direct steric occlusion of the active site by the C-terminal residues of the pro region [Sohl, J. L., et al. (1997) Biochemistry 36, 3894-3904]. Through mutagenesis and structure-function analyses we have begun to investigate the mechanism by which the pro region acts as a single turnover catalyst to facilitate folding of the mature protease. Of central interest has been mapping the interface between the pro region and the protease and identifying interactions critical for stabilizing the rate-limiting folding transition state. Progressive C-terminal deletions of the pro region were found to have drastic effects on the rate at which the pro region folds the protease but surprisingly little effect on inhibition of protease activity. The observed kinetic data strongly support a model in which the detailed interactions between the pro region C-terminus and the protease are remarkably similar to those of known substrate/inhibitor complexes. Further, mutation of two protease residues near the active site have significant effects on stabilization of the folding transition state (kcat) or in binding to the folding intermediate (KM). Our results suggest a model for the alpha-lytic protease pro region-mediated folding reaction that may be generally applicable to other pro region-dependent folding reactions.     

On the pursuit of sound science for the betterment of the American Indian community: Reply to Beals et al. (2009).

The authors of this reply argue that ongoing criticism of existing theories, the development of alternative theories, and empirical theory tests offer the best chance for advancing American Indian research. The authors therefore note their appreciation for the comments of J. Beals et al. (see record 2009-02580-012). The authors nevertheless disagree with many of the specific claims of Beals et al., noting that in their original article (see record 2007-06095-002), (a) the characterization of the existing literature on reservation-dwelling American Indian drinking was accurate; (b) no argument made by Beals et al. undermines their theoretical contention that there is a relative lack of contingency between access to basic life reinforcers and sobriety on many reservations; (c) the theory was developed in a responsible manner, specifically by a reservation-tied American Indian, and was reviewed by a reservation leadership team, a cultural consultant, and reviewers for this journal, at least one of whom consulted leaders of other reservations; and (d) the theory was based on previous interdisciplinary theory development. The authors encourage the development and testing of new, alternative theories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An Alternative Perspective on von Winterfeldt et al.'s (1997) Test of Consequence Monotonicity.

D. von Winterfeldt, N.-K. Chung, R. D. Luce, and Y. Cho (see record 1997-03378-008) provided several tests for consequence monotonicity of choice or judgment, using certainty equivalents of gambles. The authors reaxiomatized consequence monotonicity in a probabilistic framework and reanalyzed von Winterfeldt et al.'s main experiment via a bootstrap method. Their application offers new insights into consequence monotonicity as well as into von Winterfeldt et al.'s 3 experimental paradigms: judged certainty equivalents (JCE), QUICKINDIFF, and parameter estimation by sequential testing (PEST). For QUICKINDIFF, the authors found no indication of violations of "random consequence monotonicity." This sharply contrasts the findings of von Winterfeldt et al., who concluded that axiom violations were the most pronounced under that procedure. The authors found potential evidence for violations in JCE and certainty equivalents derived from PEST. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ovarian Hormones and Cognition in the Aged Female Rat: II. Progesterone Supplementation Reverses the Cognitive Enhancing Effects of Ovariectomy.

The authors hypothesized that the progesterone component of some hormone replacement therapies in women is detrimental to cognition. A previous study showed that ovariectomy (ovx) in aged rats enhanced spatial working memory and decreased elevated progesterone levels (H. A. Bimonte-Nelson, R. S. Singleton, C. L. Hunter, et al., 2003). The current study evaluated whether progesterone administration counteracts these cognitive enhancing effects of ovx. Aged sham and aged ovx rats given progesterone exhibited compromised learning of the working and reference memory components of the task, and made more working memory errors on the latter testing days compared with aged ovx rats not given progesterone. Results suggest that whereas ovx of the aged female rat enhances learning and the ability to handle numerous items of spatial working memory information, progesterone is detrimental to these aspects of performance. These findings may speak to studies in menopausal women which suggest that combination hormone therapies have a negative impact on cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clarifying the nature of the distinctiveness by domain interaction in conceptual structure: Comment on Cree, McNorgan, and McRae (2006).

The conceptual structure account of semantic memory (CSA; L. K. Tyler & H. E. Moss, 2001) claims that feature correlation (the degree to which features co-occur) and feature distinctiveness (the number of concepts in which a feature occurs) interact with domains of knowledge (e.g., living vs. nonliving) such that the distinctive features of nonliving things are more highly correlated than the distinctive features of living things. Evidence for (B. Randall, H. E. Moss, J. M. Rodd, M. Greer, & L. K. Tyler, 2004) and against this claim (G. S. Cree, C. McNorgan, & K. McRae, 2006) has been reported. This comment outlines the CSA, discusses Cree et al.'s (2006) critiques of the Randall et al. (2004) experiments and the CSA, and reports new analyses of property norm and behavioral data, which replicate the results reported by Randall et al. (2004). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Confirmatory factor analyses of academic self-concept scales: Reply to Marsh and Yeung (1997).

H. W. Marsh and A. S. Yeung (1997) criticized the conclusion of S. M. Simpson, B. G. Licht, R. K. Wagner, and S. R. Stader (1996) that children differentiate their perceived ability, near-future expectancies, and distant-future expectancies within academic domains. They argued that Simpson et al.'s questionnaire items and confirmatory factor analytic (CFA) approach were problematic and that their conclusion was inconsistent with research on academic self-concept. The authors of the present article argue that this inconsistency is because items on academic self-concept scales are not adequate for answering the questions addressed by Simpson et al., and that Simpson et al.'s conclusion is quite consistent with 2 other important lines of research. Further, the authors argue that the criticisms of Simpson et al.'s items and CFA approach are unfounded and conclude that Marsh and Yeung inadvertently provided further support for Simpson et al.'s conclusion that current academic self-concept theories should be extended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tolman's cognitive analyses: Predecessors of current approaches in psychology.

Comments on an article by E. C. Tolman et al (see PA, Vols 20:2297 and 12366) using rats in mazes to examine the cognitive mechanisms used to represent space and direct movement through it. The popularity of maze procedures to assess memory continues to illustrate the usefulness of these techniques. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A meta-analytical structural equations analysis of a model of employee turnover.

Combined meta-analysis with structural equations modeling (SEM) to validate the W. H. Mobley et al (1978) turnover theory as well as alternative structural networks proposed by A. Dalessio et al (1986), P. W. Hom et al (1984), and B. D. Bannister and R. W. Griffeth (1986). The authors aggregated correlations from 17 studies (N?=?5,013 employees), correcting for unreliability and sampling error. Then they used SEM to assess the models, comparing their relative fits to data. SEM analyses corroborated the Mobley et al model better than did past research, but these analyses also showed that the Dalessio et al and the Hom et al theories explained sample data more plausibly. Additional SEM tests found that turnover base rates, time lags between turnover and model assessments, unemployment rates, and occupational differences moderated the models' pathways. The present findings suggest various implications for these theories and for turnover research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Note on "Adverse impact from a psychometric perspective."

G. H. Ironson et al (see record 1982-29410-001) recommended the use of test characteristic curves (TCCs) in the study of adverse-impact ratios in selection. They demonstrated that a linear transformation of the Rasch ability estimate could reduce the incidence of adverse impact from the level that would result from the use of raw scores. The present authors reanalyzed their data and concluded that both the raw score scale and the ability estimates yield similar adverse-impact results. However, the authors agree with the Ironson et al proposal that relative adverse-impact ratios from different tests should be defined with TCCs because level of adverse impact can be influenced by the shape of TCCs. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)