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Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti-LINGO-1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO-1. In this study, we aim to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10-month-old male amyloid-β (Aβ) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti-LINGO-1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y-maze tests, and Aβ deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti-LINGO-1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO-1 positive cells, decreased Aβ deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO-1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO-1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aβ deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO-1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO-1 might be a potential therapeutic strategy for AD., (© 2022 Wiley Periodicals LLC.)

Depression is a mental illness which is harmful seriously to the society. This study investigated the effects of fluoxetine on the CNPase + oligodendrocytes in hippocampus of the depressed rats to explore the new target structure of antidepressants. Male Sprague-Dawley rats were used to build chronic unpredictable stress (CUS) depressed model of rats. Then, the depressed rats were divided into the CUS standard group and the CUS + fluoxetine (CUS/FLX) group. The CUS/FLX group was treated with fluoxetine at dose of 5 mg/(kg·d) from the fifth week to seventh week. After 7 weeks CUS intervention, the sucrose preference of the CUS standard group was significantly lower than that of the control group and the CUS/FLX group. The stereological results showed that the total number of the CNPase + cells in the CA1, CA3, and DG subfield of the hippocampus in the CUS standard group were significantly decreased, when compared with the CNPase + cells in the control group. However, the total number of the CNPase + cells in the CA1 and CA3 subfield of the hippocampus in the CUS standard group was significantly decreased when it compared with CNPase + cells in the CUS/FLX group. Therefore, fluoxetine might prevent the loss of CNPase + oligodendrocytes in CA1 and CA3 subfields of hippocampus of the depressed rats. The oligodendrocytes in hippocampus may play an important role in the pathogenesis of depression. The current result might provide structural basis for the future studies that search for new antidepressant strategies., (© 2020 Wiley Periodicals, Inc.)

Chronic stress can induce cognitive impairment, and synapse number was significantly decreased in the hippocampus of rats suffering from chronic stress. Lingo‐1 is a potent negative regulator of axonal outgrowth and synaptic plasticity. In the current study, the effects of anti‐Lingo‐1 antibody on the spatial learning and memory abilities and hippocampal synapses of stressed rats were investigated. After 4 weeks of stress exposure, the model group was randomly divided into a chronic stress group and an anti‐Lingo‐1 group. Then, the anti‐Lingo‐1 group rats were treated with anti‐Lingo‐1 antibody (8 mg/kg) for 3 weeks. The effects of anti‐Lingo‐1 antibody on the spatial learning and memory abilities were investigated with the Morris water maze test. Immunohistological staining and an unbiased stereological method were used to estimate the total number of dendritic spine synapses in the hippocampus. At the behavioral level, after 3 weeks of treatment, the anti‐Lingo‐1 group rats displayed significantly more platform location crossings in the Morris water maze test than the chronic stress group rats. Anti‐Lingo‐1 significantly prevented the declines in dendritic spine synapses and postsynaptic density protein‐95 (PSD‐95) expression in the dentate gyrus and the CA1 and CA3 regions of the hippocampus. The present results indicated that anti‐Lingo‐1 antibody may be a safe and effective drug for alleviating memory impairment in rats after chronic stress and protecting synapses in the hippocampus of stressed rats. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline. Previous studies have reported that the syndrome of AD begins with subtle alterations in hippocampal synapses prior to frank neuronal degeneration. It has recently been reported that fluoxetine (FLX) shows positive effects on AD patients who have depression and anxiety. However, it is unclear whether FLX can affect the pathogenesis of AD mice in the early stage of AD. To address this question, 8‐month‐old male APP/PS1 double‐transgenic AD mice were administered a 10‐week course of FLX (10 mg/kg/day) injections. Then, spatial learning and memory were evaluated using a Morris water maze test. Immunohistological staining and an unbiased stereological method were used to estimate the total number of dendritic spine synapses in the hippocampus. We found that FLX significantly shortened the mean escape latencies of the 10‐month‐old mice; reduced the elevated levels of soluble Aβ40, Aβ42, and amyloid plaques in the hippocampus; and prevented the decrease in dendritic spine synapses and in postsynaptic protein PSD‐95 density in the dentate gyrus, CA1/2 and CA3 regions of the hippocampus. Our results indicate that reversing synaptic impairment might be considered a promising therapeutic approach for alleviating the cognitive deficits associated with early AD. Moreover, our results suggest that FLX may be a safe and effective drug for delaying the progress of AD, which might provide a starting point for further research into new preventative measures and treatments for AD. Using the unbiased stereological methods, we found that FLX prevented the decrease in dendritic spine synapses in the dentate gyrus, CA1/2 and CA3 regions of the hippocampus in the early Alzheimer's disease. This might provide a starting point for further research into new preventative measures and treatments for AD. [ABSTRACT FROM AUTHOR]