Anxiety in Alzheimer's disease rats is independent of memory and impacted by genotype, age, sex, and exercise.

INTRODUCTION: Alzheimer's disease (AD) is characterized by cognitive impairments; however, heightened anxiety often accompanies and, in some cases, exacerbates cognitive its. The present study aims to understand the influence of multiple variables on anxiety-like behavior in TgF344-AD rats and determine whether anxiety impacts memory performance. METHODS: An elevated plus maze was used to assess anxiety-like behavior in the established colony (n = 107). Influences of age, sex, genotype, and exercise on anxiety were evaluated via multiple linear regression. Correlation analysis evaluated the relationship between anxiety and memory performance. RESULTS: Age (P < 0.05) and AD genotype (P < 0.001) were associated with increasing anxiety, while exercise (P < 0.05) was associated with decreasing anxiety. Female AD animals displayed more anxiety-like behavior versus wild-type female (P < 0.001) and AD male (P < 0.05) littermates. DISCUSSION: Concluding that while factors such as age, sex, AD genotype, and training status can impact anxiety levels in the TgF344-AD model, anxiety level did not impact memory performance. HIGHLIGHTS: Increased anxiety-like behavior in TgF344-AD rats does not correlate with declines in memory performance. Predictors of higher anxiety-like behaviors in the TgF344-AD rat include age, Alzheimer's disease (AD) genotype, and sex with female AD animals experiencing greater anxiety compared to female wild-type or male AD. Exercise training leads to decreased anxiety-like behaviors in the TgF344-AD rat.

Delayed Muscle Activity in Stroke Survivors with Upper-Limb Hemiparesis.

Stroke is the leading cause of disability worldwide, and nearly 80% of stroke survivors suffer from upper-limb hemiparesis. Myoelectric exoskeletons can restore dexterity and independence to stroke survivors with upper-limb hemiparesis. However, the ability of patients to dexterously control myoelectric exoskeletons is limited by an incomplete understanding of the electromyographic (EMG) hallmarks of hemiparesis, such as muscle weakness and spasticity. Here we show that stroke survivors with upper-limb hemiparesis suffer from delayed voluntary muscle contraction and delayed muscle relaxation. We quantified the time constants of EMG activity associated with initiating and terminating voluntary hand grasps and extensions for both the paretic and non-paretic hands of stroke survivors. We found that the initiation and termination time constants were greater on the paretic side for both hand grasps and hand extensions. Notably, the initiation time constant during hand extension was approximately three times longer for the paretic hand than for the contralateral non-paretic hand (0.618 vs 0.189 s). We also show a positive correlation between the initiation and termination time constants and clinical scores on the Modified Ashworth Scale. The difficulty stroke survivors have in efficiently modulating their EMG presents a challenge for appropriate control of assistive myoelectric devices, such as exoskeletons. This work constitutes an important step towards understanding EMG differences after stroke and how to accommodate these EMG differences in assistive myoelectric devices. Real-time quantitative biofeedback of EMG time constants may also have broad implications for guiding rehabilitation and monitoring patient recovery.Clinical Relevance- After a stroke, muscle activity changes, and these changes make it difficult to use muscle activity to drive assistive and rehabilitative technologies. We identified slower muscle contraction and muscle relaxation as a key difference in muscle activity after a stroke. This quantifiable difference in muscle activity can be used to develop better assistive technologies, guide rehabilitation, and monitor patient recovery.

Astrocytes infected with Chlamydia pneumoniae demonstrate altered expression and activity of secretases involved in the generation of ß-amyloid found in Alzheimer disease.

BACKGROUND: Epidemiologic studies strongly suggest that the pathophysiology of late-onset Alzheimer disease (AD) versus early-onset AD has environmental rather than genetic causes, thus revealing potentially novel therapeutic targets to limit disease progression. Several studies supporting the "pathogen hypothesis" of AD demonstrate a strong association between pathogens and the production of ß-amyloid, the pathologic hallmark of AD. Although the mechanism of pathogen-induced neurodegeneration of AD remains unclear, astrocytes, a key player of the CNS innate immune response and producer/metabolizer of ß-amyloid, have been implicated. We hypothesized that Chlamydia pneumoniae infection of human astrocytes alters the expression of the amyloid precursor protein (APP)-processing secretases, ADAM10, BACE1, and PSEN1, to promote ß-amyloid formation. Utilizing immunofluorescent microscopy, molecular, and biochemical approaches, these studies explore the role of an intracellular respiratory pathogen, Chlamydia pneumoniae, as an environmental trigger for AD pathology. Human astrocytoma cells in vitro were infected with Chlamydia pneumoniae over the course of 6-72 h. The gene and protein expression, as well as the enzymatic activity of non-amyloidogenic (ADAM10), and pro-amyloidogenic (BACE1 and PSEN1) secretases were qualitatively and quantitatively assessed. In addition, the formation of toxic amyloid products as an outcome of pro-amyloidogenic APP processing was evaluated through various modalities. RESULTS: Chlamydia pneumoniae infection of human astrocytoma cells promoted the transcriptional upregulation of numerous genes implicated in host neuroinflammation, lipid homeostasis, microtubule function, and APP processing. Relative to that of uninfected astrocytes, BACE1 and PSEN1 protein levels were enhanced by nearly twofold at 48-72 h post-Chlamydia pneumoniae infection. The processing of APP in Chlamydia pneumoniae-infected astrocytes favors the pro-amyloidogenic pathway, as demonstrated by an increase in enzymatic activity of BACE1, while that of ADAM10 was decreased. Fluorescence intensity of ß-amyloid and ELISA-quantified levels of soluble-APP by products revealed temporally similar increases, confirming a BACE1/PSEN1-mediated processing of APP. CONCLUSIONS: Our findings suggest that Chlamydia pneumoniae infection of human astrocytes promotes the pro-amyloidogenic pathway of APP processing through the upregulation of expression and activity of ß-secretase, upregulated expression of γ-secretase, and decreased activity of α-secretase. These effects of astrocyte infection provide evidence for a direct link between Chlamydia pneumoniae and AD pathology.

Fluorescence-guided stereotactic biopsy: a proof-of-concept study.

OBJECTIVEAccurate histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining suspicious tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in some cases. Failure to obtain diagnostic tissue can delay initiation of treatment and may result in further invasive procedures for patients. In this study, the authors sought to determine if the coupling of in vivo optical imaging with an STB system is an effective method for identification of diagnostic tissue at the time of biopsy.METHODSA minimally invasive fiber optic imaging system was developed by coupling a 0.65-mm-diameter coherent fiber optic fluorescence microendoscope to an STB system. Human U251 glioma cells were transduced for stable expression of blue fluorescent protein (BFP) to produce U251-BFP cells that were utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by fluorescein sodium (FNa) was quantified with fluorescence microscopy. In vivo, transgenic athymic rats implanted with U251-BFP cells (n = 4) were utilized for experiments. Five weeks postimplantation, the rats received 5-10 mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65-mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest ipsilateral and contralateral to tumor implantation were obtained and quantified.RESULTSLive-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2 = 0.91, p < 0.001). Normalized to background, in vivo FNa-mediated fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (301.7 ± 34.18 relative fluorescence units, p < 0.001). Fluorescence intensity measured from the tumor margin was not significantly greater than that from normal brain (p = 0.89). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor.CONCLUSIONSThe authors found that in vivo fluorescence imaging with an STB needle containing a submillimeter-diameter fiber optic fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. These results were confirmed in vivo with positive control cells and by post hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies.

Developmental relations between vocabulary knowledge and reading comprehension: a latent change score modeling study.

The present study followed a sample of first-grade (N = 316, Mage = 7.05 at first test) through fourth-grade students to evaluate dynamic developmental relations between vocabulary knowledge and reading comprehension. Using latent change score modeling, competing models were fit to the repeated measurements of vocabulary knowledge and reading comprehension to test for the presence of leading and lagging influences. Univariate models indicated growth in vocabulary knowledge, and reading comprehension was determined by two parts: constant yearly change and change proportional to the previous level of the variable. Bivariate models indicated previous levels of vocabulary knowledge acted as leading indicators of reading comprehension growth, but the reverse relation was not found. Implications for theories of developmental relations between vocabulary and reading comprehension are discussed.

Incorporating RTI in a Hybrid Model of Reading Disability.

The present study seeks to evaluate a hybrid model of identification that incorporates response-to-intervention (RTI) as a one of the key symptoms of reading disability. The one-year stability of alternative operational definitions of reading disability was examined in a large scale sample of students who were followed longitudinally from first to second grade. The results confirmed previous findings of limited stability for single-criterion based operational definitions of reading disability. However, substantially greater stability was obtained for a hybrid model of reading disability that incorporates RTI with other common symptoms of reading disability.

Developmental Relations between Reading and Writing at the Word, Sentence and Text Levels: A Latent Change Score Analysis.

Relations between reading and writing have been studied extensively but the less is known about the developmental nature of their interrelations. This study applied latent change score modeling to investigate longitudinal relations between reading and writing skills at the word, sentence and text levels. Latent change score models were used to compare unidirectional pathways (reading-to-writing and writing-to-reading) and bidirectional pathways in a test of nested models. Participants included 316 boys and girls who were assessed annually in grades 1 through 4. Measures of reading included pseudo-word decoding, sentence reading efficiency, oral reading fluency and passage comprehension. Measures of writing included spelling, a sentence combining task and writing prompts. Findings suggest that a reading-to-writing model better described the data for the word and text levels of language, but a bidirectional model best fit the data at the sentence level.

Developmental relations between reading fluency and reading comprehension: a longitudinal study from Grade 1 to Grade 2.

From a developmental framework, relations among list reading fluency, oral and silent reading fluency, listening comprehension, and reading comprehension might be expected to change as children's reading skills develop. We examined developmental relations among these constructs in a latent-variable longitudinal study of first and second graders. Results showed that list reading fluency was uniquely related to reading comprehension in Grade 1, but not in Grade 2, after accounting for text reading fluency (oral or silent) and listening comprehension. In contrast, text reading fluency was uniquely related to reading comprehension in Grade 2, but not in Grade 1, after accounting for list reading fluency and listening comprehension. When oral reading fluency and silent reading fluency were compared, oral reading fluency was uniquely related to reading comprehension after accounting for silent reading fluency in Grade 1, whereas silent reading fluency was uniquely related to reading comprehension after accounting for oral reading fluency in Grade 2.

How word frequency modulates masked repetition priming: an ERP investigation.

The present study used event-related potentials (ERPs) to provide precise temporal information about the modulation of masked repetition priming effects × word frequency during the course of target word recognition. Contrary to the pattern seen with behavioral response times in prior research, we predicted that high-frequency words should generate larger and earlier peaking repetition priming effects than low-frequency words in the N400 time window. This prediction was supported by the results of two experiments. Furthermore, repetition priming effects in the N250 time window were found for low-frequency words in both experiments, whereas for high-frequency words these effects were seen only at the shorter (50 ms stimulus onset asynchrony [SOA]) used in Experiment 2, and not in Experiment 1 (70 ms SOA). We explain this pattern as resulting from reset mechanisms operating on the form representations activated by prime stimuli when primes and targets are processed as separate perceptual events.