The immune marker CD68 correlates with cognitive impairment in normally aged rats

Farso, Mark; Ménard, Caroline; Colby-Milley, Jessica; Quirion, Rémi

doi:10.1016/j.neurobiolaging.2013.02.008

Cited by 15 publications

(18 citation statements)

References 38 publications

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“…We observed MHC class II and CD68‐positive microglia in all sections obtained from brains of aged individuals (>62 years, Table ), which included Braak & Braak stages I/II, Braak & Braak stages III‐VI and four cases of sepsis to distinguish activated from dystrophic microglia (Streit et al, ) and aged nondemented controls (78–83 years), but rarely in young control brain sections (Figs. and ), which is in line with previous reports (Cribbs et al, ; Farso et al, ; Perry et al, ). When seen in young brains severe systemic inflammation was present.…”

Section: Discussionsupporting

confidence: 93%

Inhomogeneous distribution of Iba‐1 characterizes microglial pathology in Alzheimer's disease

Tischer

Krueger

Mueller

et al. 2016

Glia

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Microglial dystrophy has recently been described as a morphological phenotype of microglia that differs from resting and activated states by spheroid formation and cytorrhexis. In thick sections immunolabeled for HLA-DR or Iba-1 dystrophic microglial processes lose their typical, homogeneous staining pattern and appear to be fragmented or clustered. In this study, we performed double immunofluorescence and electron microscopy to determine if this labeling pattern indeed reflects complete separation of microglial processes from the soma. Using Iba-1/CD68 and Iba-1/MHC class II, as microglial markers, we observed that isolated Iba-1 fragments were still connected to each other by segments of the microglial process immune positive for CD68 or MHC class II. Ultrathin serial sections of two Iba-1 fragments which appeared to be disconnected from each other at the light microscopical level revealed a still existing "bridge" with a diameter of around 0.182 µm. Therefore, microglial dystrophy may reflect alterations of the cytoskeleton ultimately leading to slow cytorrhexis. GLIA 2016;64:1562-1572.

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Section: Discussionsupporting

confidence: 93%

Inhomogeneous distribution of Iba‐1 characterizes microglial pathology in Alzheimer's disease

Tischer

Krueger

Mueller

et al. 2016

Glia

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“…The long-term reference memory version of the MWM task (Morris, 1984) was performed as described previously to discriminate between aged rat populations according to memory status (Brouillette and Quirion, 2008;Farso et al, 2013;Gallagher et al, 2003;Lee et al, 2005;Menard and Quirion, 2012b;Rowe et al,1998).…”

Section: Morris Water Mazementioning

confidence: 99%

“…After a 2-(LE) or 1-(LOU) day rest, all animals were submitted to a reverse memory paradigm to assess reversal learning acquisition (Farso et al, 2013;Menard and Quirion, 2012b;Menard et al, 2013Menard et al, , 2014bXu et al, 2009). In this task, while the position of visual cues stayed the same, the platform was moved to the opposite quadrant of the pool.…”

Section: Reversal Learning Acquisition and Retentionmentioning

confidence: 99%

“…As previously described by our group (Brouillette and Quirion, 2008;Farso et al, 2013;Menard and Quirion, 2012b;Rowe et al, 1998) and others (Gallagher et al, 2003;Lee et al, 2005), learning acquisition curves and probe tests of aged rats were compared with those of 6-month-old adult rats to classify them as aged memoryimpaired (AI) or memory-unimpaired (AU). In the present study, 24-month-old LE rats were classified as AI when animals swam for more than 30 seconds (average of the 3 trials) to find the platform on day 5 of learning acquisition.…”

Section: Classification Criteria For Cognitive Statusmentioning

confidence: 99%

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Glutamate presynaptic vesicular transporter and postsynaptic receptor levels correlate with spatial memory status in aging rat models

Ménard

Quirion

Vigneault

et al. 2015

Neurobiology of Aging

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In humans, memory capacities are generally affected with aging, even without any reported neurologic disorders. The mechanisms behind cognitive decline are not well understood. We studied here whether postsynaptic glutamate receptor and presynaptic vesicular glutamate transporters (VGLUTs) levels may change in the course of aging and be related to cognitive abilities using various age-impaired (AI) or age-unimpaired rat strains. Twenty-four-month-old Long-Evans (LE) rats with intact spatial memory maintained postsynaptic ionotropic glutamate receptor levels in the hippocampal-adjacent cortex similar to those of young animals. In contrast, AI rats showed significantly reduced expression of ionotropic glutamate receptor GluR2, NR2A and NR2B subunits. In AI LE rats, VGLUT1 and VGLUT2 levels were increased and negatively correlated with receptor levels as shown by principal component analysis and correlation matrices. We also investigated whether glutamatergic receptors and VGLUT levels were altered in the obesity-resistant LOU/C/Jall (LOU) rat strain which is characterized by intact memory despite aging. No difference was observed between 24-month-old LOU rats and their young counterparts. Taken together, the unaltered spatial memory performance of 24-month-old age-unimpaired LE and LOU rats suggests that intact coordination of the presynaptic and postsynaptic hippocampal-adjacent cortex glutamatergic networks may be important for successful cognitive aging. Accordingly, altered expression of presynaptic and postsynaptic glutamatergic components, such as in AI LE rats, could be considered a marker of age-related cognitive deficits.

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“…The microglia plays a critical role in neuroinflammation as it represents the main type of immune cells in the brain [8]. The activation of microglia in aging models leads to the secretion of proinflammatory cytokines, which contribute to synaptic and neuronal damage as well as cognitive impairment [9,10]. …”

Section: Introductionmentioning

confidence: 99%

Rcor2 underexpression in senescent mice: a target for inflammaging?

Álvarez-López

Molina-Martínez

Castro

et al. 2014

J Neuroinflammation

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BackgroundAging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.MethodsTo assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.ResultsP8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.ConclusionsData presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

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The immune marker CD68 correlates with cognitive impairment in normally aged rats

Cited by 15 publications

References 38 publications

Inhomogeneous distribution of Iba‐1 characterizes microglial pathology in Alzheimer's disease

Inhomogeneous distribution of Iba‐1 characterizes microglial pathology in Alzheimer's disease

Glutamate presynaptic vesicular transporter and postsynaptic receptor levels correlate with spatial memory status in aging rat models

Rcor2 underexpression in senescent mice: a target for inflammaging?

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