Background: Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina. Objective: This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters. Methods: In young (2–3-month-old) and adult (6-7-month-old) 5xFAD and WT mice, we have studied the physiological response, firing rate, and burst of RGCs to various types of visual stimuli using a multielectrode array system. Results: The firing rate and burst response in 5xFAD RGCs showed hyperactivity at the early stage of AD in young mice, whereas hypoactivity was seen at the later stage of AD in adults. The physiological alterations observed in 5xFAD correlate well with an increase in the expression of glutamate in the ganglion cell layer in young and adults. GABA staining increased in the inner nuclear and plexiform layer, which was more pronounced in the adult than the young 5xFAD retina, altering the excitation/inhibition balance, which could explain the observed early hyperactivity and later hypoactivity in RGC physiology. Conclusion: These findings indicate functional changes may be caused by neurochemical alterations of the retina starting at an early stage of the AD disease.
Comparison of Autoregulatory Indexes on Spontaneous Variations with Linear Support Vector MachinesMax Chacón1, Felipe Bello1, JL Jara1, Ronney B. Panerai2: 1Departamento de Ingeniería Informática, Universidad de Santiago de Chile, Avda. Ecuador 3659, 9170124, Santiago, Chile. 2Department of Cardiovascular Science, Leicester University, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK. Linear Support Vector Machines (lSVMs) were used to model the relationship between signals of spontaneous variations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) of 16 healthy subjects in two capnic conditions: normocapnia and hypercapnia (5% CO2). Each model was trained with a section of 2.5 m of the recorded signals and evaluated by means of correlation analysis on another 2.5 m section. Signals were sampled at 0,6 s. The classic index of autoregulation (ARI) and a recently‐proposed index, named model‐free ARI (mfARI), were calculated for the step response of the models. Paired tests were applied to determine significant differences between capnic conditions and between indexes. Sensitivity and Specificity were also estimated considering that subjects in hypercapnia should exhibit impaired autoregulation and a normality threshold of 5 for both indexes. Table 1 summarizes the results. Both indexes found significant differences between capnic conditions. mfARI values were significantly lower than ARI values for subject in hypercapnia, and yielded a more balanced discrimination between normal and abnormal autoregulation. Tabla 1: Results Normocapniamean indexHypercapniamean indexDiff. between capnic statesSensitivitySpecificityCorrelation coeff.0.5930.662ARI6.2885.400p=0.01992%50%mfARI5.8633.305p=0.00169%75%Diff. between indicesp=0.055p<0.001
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