Abstract To understand the reading strategies used by deaf students, two groups of profoundly deaf individuals were tested: Group 1: users of the Brazilian Sign Language and Group 2: users of the ...Brazilian Sign Language and speech and/or lip reading. A reading test was used to assess the degree of development of logographic, alphabetic and orthographic strategies. The group of deaf students who used alternative means of communication (Group 2) showed improved performance in all psycholinguistic categories of the test in comparison to Group 1. It was observed that the use of phonology is not directly associated with good reading skills in the profoundly deaf. On the other hand, word recognition by these readers occurs via the utilization of the orthographic strategy, which proved to be efficient.
Resumo Para compreender as estratégias de leitura utilizadas por indivíduos com surdez profunda, o presente estudo investigou dois grupos: Grupo 1, constituído por usuários da Libras – Língua Brasileira de Sinais; e Grupo 2, composto por indivíduos que, além da Libras, usam recursos de oralização e/ou leitura labial. Por meio do Teste de Competência de Leitura de Palavras, foi avaliado o grau de desenvolvimento das estratégias logográfica, alfabética e ortográfica. Em comparação ao Grupo 1, o grupo de surdos que utiliza meios alternativos de comunicação (Grupo 2) apresentou desempenho superior em todas as categorias psicolinguísticas do teste. Observou-se que o uso da fonologia não está diretamente associado à boa habilidade de leitura em surdos profundos e que o reconhecimento de palavras por esses leitores se dá por meio da utilização da estratégia ortográfica, que se mostrou eficiente.
Few studies have addressed the effects of caffeine in the puberty and/or adolescence in a sex dependent manner. Considering that caffeine intake has increased in this population, we investigated the ...behavioral and synaptic proteins changes in pubescent male and female rats after maternal consumption of caffeine. Adult female Wistar rats started to receive water or caffeine (0.1 and 0.3g/L in drinking water; low and moderate dose, respectively) during the active cycle at weekdays, two weeks before mating. The treatment lasted up to weaning and the offspring received caffeine until the onset of puberty (30–34days old). Behavioral tasks were performed to evaluate locomotor activity (open field task), anxious-like behavior (elevated plus maze task) and recognition memory (object recognition task) and synaptic proteins levels (proBDNF, BDNF, GFAP and SNAP-25) were verified in the hippocampus and cerebral cortex. While hyperlocomotion was observed in both sexes after caffeine treatment, anxiety-related behavior was attenuated by caffeine (0.3g/L) only in females. While moderate caffeine worsened recognition memory in females, an improvement in the long-term memory was observed in male rats for both doses. Coincident with memory improvement in males, caffeine increased pro- and BDNF in the hippocampus and cortex. Females presented increased proBDNF levels in both brain regions, with no effects of caffeine. While GFAP was not altered, moderate caffeine intake increased SNAP-25 in the cortex of female rats. Our findings revealed that caffeine promoted cognitive benefits in males associated with increased BDNF levels, while females showed less anxiety. Our findings revealed that caffeine promotes distinct behavioral outcomes and alterations in synaptic proteins during brain development in a sex dependent manner.
•Female pubescent rats were more responsive to caffeine-induced hyperlocomotion.•Caffeine worsened recognition memory in female pubescent rats.•Recognition memory was improved by caffeine in male pubescent rats.•Anxiety-related behavior was attenuated by caffeine in female pubescent rats.•Both pro- and BDNF increased in the hippocampus after caffeine treatment in males.
Glutamatergic neurotransmission system dysregulation may play an important role in the pathophysiology of Alzheimer's disease (AD). However, reported results on glutamatergic components across brain ...regions are contradictory. Here, we conducted a systematic review with meta-analysis to examine whether there are consistent glutamatergic abnormalities in the human AD brain. We searched PubMed and Web of Science (database origin-October 2023) reports evaluating glutamate, glutamine, glutaminase, glutamine synthetase, glutamate reuptake, aspartate, excitatory amino acid transporters, vesicular glutamate transporters, glycine, D-serine, metabotropic and ionotropic glutamate receptors in the AD human brain (PROSPERO #CDRD42022299518). The studies were synthesized by outcome and brain region. We included cortical regions, the whole brain (cortical and subcortical regions combined), the entorhinal cortex and the hippocampus. Pooled effect sizes were determined with standardized mean differences (SMD), random effects adjusted by false discovery rate, and heterogeneity was examined by I
statistics. The search retrieved 6 936 articles, 63 meeting the inclusion criteria (N = 709CN/786AD; mean age 75/79). We showed that the brain of AD individuals presents decreased glutamate (SMD = -0.82; I
= 74.54%; P < 0.001) and aspartate levels (SMD = -0.64; I
= 89.71%; P = 0.006), and reuptake (SMD = -0.75; I
= 83.04%; P < 0.001. We also found reduced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)-GluA2/3 levels (SMD = -0.63; I
= 95.55%; P = 0.046), hypofunctional N-methyl-D-aspartate receptor (NMDAR) (SMD = -0.60; I
= 91.47%; P < 0.001) and selective reduction of NMDAR-GluN2B subunit levels (SMD = -1.07; I
= 41.81%; P < 0.001). Regional differences include lower glutamate levels in cortical areas and aspartate levels in cortical areas and in the hippocampus, reduced glutamate reuptake, reduced AMPAR-GluA2/3 in the entorhinal cortex, hypofunction of NMDAR in cortical areas, and a decrease in NMDAR-GluN2B subunit levels in the entorhinal cortex and hippocampus. Other parameters studied were not altered. Our findings show depletion of the glutamatergic system and emphasize the importance of understanding glutamate-mediated neurotoxicity in AD. This study has implications for the development of therapies and biomarkers in AD.
Background
Glial Fibrillary Acidic Protein (GFAP) is an intermediate filament expressed almost exclusively in astrocytes, and it is usually overexpressed in reactive astrocytes. We have previously ...shown that astrocytes play a critical role in brain energy metabolism and are significant contributors to the 18FFDG‐PET signal. The cortex is majorly composed of glial cells, whereas the cerebellum is predominantly composed of neurons. In light of this, whether GFAP levels in the brain tissue are associated with 18FFDG‐PET signal remains unknown. Thus, we aimed to investigate the associations between cortical and cerebellar GFAP levels with brain glucose metabolism in a rat model of Alzheimer’s disease.
Methods
Brain metabolism of ten‐month‐old TgF344‐AD (n=8) and wild‐type (WT,n=6) rats was assessed with 18FFDG‐PET. Then, GFAP RNA levels were quantified in the frontal cortex (CXF), temporoparietal cortex (CXTP), and cerebellum (CB) using qRT‐PCR. The 18FFDG‐PET standardized uptake ratio (SUVr) was calculated using pons as the reference region. T‐tests were used to assess the differences between groups in GFAP RNA expression levels and regional brain 18FFDG‐PET. Comparisons were conducted using t‐statistical analyses at voxel level (RMINC). Differences were considered statistically significant at p<0.05 (t>2).
Results
No differences between groups were found in the whole brain FDG metabolism or regions of interest (CXF, CXTP, and CB;t(13)<2). At the voxel level, we identified small cortical hypermetabolic clusters in the TgF344‐AD rats (t(13)=5.55, local maxima). The GFAP RNA was increased in the CXTP of TgF344‐AD rats (p=0.001). No significant differences were found between groups in GFAP RNA levels in other brain regions evaluated. Interestingly, we found positive correlations between 18FFDG‐PET metabolism and the GFAP RNA expression in the CXTP (local maxima, t(13)=8.33;Fig.1a) and CXF (local maxima, t(13)=4.82;Fig.1b). By contrast, 18FFDG metabolism did not associate with GFAP RNA expression levels in the CB (t(13)<2;Fig.1c).
Conclusion
GFAP RNA levels were increased in the CXTP of TgF344‐AD rats, which may indicate early astrocyte reactivity. GFAP RNA expression was associated with 18FFDG metabolism only in cortical regions, suggesting that astrocytes may have major roles in cortical glucose uptake, but not in cerebellum.
Background
Imaging and fluid biomarkers have helped to reconceptualize Alzheimer’s Disease (AD) as a continuum. However, the biological interpretation of each AD biomarker remains under ...investigation. In this context, animal models that mimic the AD dynamic biomarkers cascade model present high translational value and can be used to refine our interpretation of biomarker findings. In light of this, we longitudinally evaluated 18FFDG‐PET imaging, cerebrospinal fluid (CSF) glial and immune biomarkers, and behavior in the TgF344‐AD rat, a model harboring human APP/PS1 mutations.
Methods
TgF344‐AD rats and wild‐type littermates were longitudinally evaluated at 3, 6, 9, and 12 months of age. Rats underwent 18FFDG‐microPET scans, behavioral tasks (Y‐maze and novel objective recognition) and CSF samplings. The 18FFDG SUVr was calculated with pons as the reference region. CSF glial and immune markers were measured by multiplex ELISA. A cross‐sectional cohort was used to measure cortical glutamate uptake (ex‐vivo slices) at the same time points. Further examination of astrocyte proteins immunocontent was conducted at 9 months of age.
Results
At 3, 6 and 12 months, no changes in 18FFDG metabolism were found. At 9 months of age, we identified a significant cortical hypermetabolism in the TgF344‐AD and a decline in alternance during the Y‐maze task. CSF GFAP levels were elevated at 6 and 9 months of age, while CSF S100B was decreased at 9 months of age. Additionally, the cortical and hippocampal glutamate uptake and GFAP cortical immunocontent were increased at 9 and 12 months of age. The recognition memory and CSF inflammatory markers (sTREM2, IL‐6, TNF‐α, IL‐10) were not altered in any of the ages evaluated.
Conclusion
Our results suggest that the TgF344‐AD rat model is suitable for studying astrocytic adaptations during early stages of amyloidosis in the rat brain. These adaptations include cortical glucose hypermetabolism, fluid biomarker evidence of reactive astrogliosis, and spatial memory impairment with concurrent abnormalities in astrocyte glutamate uptake in the cortex and hippocampus. Due to the critical role of astrocytes in brain glucose handling, our findings suggest that astrocyte reactivity could be driving glucose hypermetabolism and memory impairment early in the disease course.
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