Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation

Vijayan, Vijaya K.; Gedes, James W.; Anderson, Kevin J.; Chang-Chui, Helena; Ellis, William G.; Cotman, Carl W.

doi:10.1016/0014-4886(91)90115-s

Cited by 70 publications

(28 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A previous report demonstrated that affected patients present with a significant increase in astrocytosis in their hippocampal [42] and cortical areas [43] compared to non-demented patients. In our APP SL mouse model we observed a profound increase only in neocortical but not in hippocampal reactive astrocyte levels up to an age of 12 months.…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivomodel of Alzheimer’s disease

Löffler

Flunkert

Havas

et al. 2014

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundBeyond cognitive decline, Alzheimer’s disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect the broad spectrum of disease-specific alterations, the APPSL mouse model is well known to display early plaque formation and to exhibit spatial learning and memory deficits. However, important neuropathological features, such as neuroinflammation and lipid peroxidation, and their progression over age, have not yet been described in this AD mouse model.MethodsHippocampal and neocortical tissues of APPSL mice at different ages were evaluated. One hemisphere from each mouse was examined for micro- and astrogliosis as well as concomitant plaque load. The other hemisphere was evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive substances (TBARS) assay), changes in Aβ abundance (Aβ38, Aβ40 and Aβ42 analyses), as well as determination of aggregated Aβ content (Amorfix A4 assay). Finally, correlation analyses were performed to illustrate the time-dependent correlation between neuroinflammation and Aβ load (soluble, insoluble, fibrils), or lipid peroxidation, respectively.ResultsAs is consistent with previous findings, neuroinflammation starts early and shows strong progression over age in the APPSL mouse model. An analyses of concomitant Aβ load and plaque deposition revealed a similar progression, and high correlations between neuroinflammation markers and soluble or insoluble Aβ or fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by TBARS levels, correlates well with neuroinflammation in the neocortex but not the hippocampus. The hippocampal lipid peroxidation correlated strongly with the increase of LOC positive fiber load, whereas neocortical TBARS levels were unrelated to amyloidosis.ConclusionsThese data illustrate for the first time the progression of major AD related neuropathological features other than plaque load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and astrocytosis are prominent aspects of this AD mouse model. The strong correlation of neuroinflammation with amyloid burden and lipid peroxidation underlines the importance of these pathological factors for the development of AD. The new finding of a different relation of lipid peroxidation in the hippocampus and neocortical regions show that the model might contribute to the understanding of complex pathological mechanisms and their interplay in AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivomodel of Alzheimer’s disease

Löffler

Flunkert

Havas

et al. 2014

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…In human brain injury (Castejón, 1998; Hausmann et al, 2000), stroke (Martí-Fàbregas et al, 2010), and in vascular dementia (Delacourte and Buée, 1989; Vijayan et al, 1991) an increased presence of reactive, hypertrophic astrocytes has been observed. Moreover, dysfunction in the neurovascular unit, in which astrocytes play a prominent role, has also been suggested for vascular diseases (see review, Lecrux and Hamel, 2011).…”

Section: Discussionmentioning

confidence: 99%

Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function

Lewis

Thomas

Selvamani

et al. 2012

Neurobiology of Aging

View full text Add to dashboard Cite

In middle-aged female rats, focal ischemia leads to a larger cortical infarction as compared with younger females. To determine if stroke-induced cytotoxicity in middle-aged females was associated with impaired astrocyte function, astrocytes were harvested and cultured from the ischemic cortex of young and middle-aged female rats. Middle-aged astrocytes cleared significantly less glutamate from media as compared with young female astrocytes. Furthermore, astrocyte-conditioned media from middle-aged female astrocytes induced greater migration of peripheral blood monocyte cells (PBMCs) and expressed higher levels of the chemoattractant macrophage inflammatory protein-1 (MIP-1). Middle-aged astrocytes also induced greater migration of neural progenitor cells (NPCs), however, their ability to promote neuronal differentiation of neural progenitor cells was similar to young astrocytes. In males, where cortical infarct volume is similar in young and middle-aged animals, no age-related impairment was observed in astrocyte function. These studies show that the aging astrocyte may directly contribute to infarct severity by inefficient glutamate clearance and enhanced cytokine production and suggest a cellular target for improved stroke therapy among older females.

show abstract

“…They are multifunctional housekeeping cells that maintain tight control of local ion and pH homeostasis, deliver glucose, provide metabolic substrates and clear neuronal waste, establishing the functional as well as the structural architecture of the brain (Nedergaard et al, 2003). They also exert important roles in genetic and neoplasic diseases, as well as in CNS infections, degeneration and trauma (Bignami and Dahl, 1976;Vijayan et al, 1991;Kindy et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Morphological Alterations and Cell Death Provoked by the Branched-Chain α-Amino Acids Accumulating in Maple Syrup Urine Disease in Astrocytes from Rat Cerebral Cortex

et al. 2005

View full text Add to dashboard Cite

1. Maple syrup urine disease (MSUD) is an inherited metabolic disorder predominantly characterized by neurological dysfunction and cerebral atrophy whose patophysiology is poorly known. 2. We investigated here whether the branched-chain amino acids (BCAA) leucine (Leu), isoleucine (Ile) and valine (Val), which are the biochemical hallmark of this disorder, could alter astrocyte morphology and cytoskeleton reorganization by exposing cultured astrocytes from cerebral cortex of neonatal rats to various concentrations of the amino acids. A change of cell morphology from the usual polygonal to the appearance of fusiform or process-bearing cells was caused by the BCAA. Cell death was also observed when astrocytes were incubated in the presence of BCAA for longer periods. 3. Val-treated astrocytes presented the most dramatic morphological alterations. Immunocytochemistry with anti-actin and anti-GFAP antibodies revealed that all BCAA induced reorganization of actin and GFAP cytoskeleton. In addition, lysophosphatidic acid, an activator of RhoA GTPase pathway, was able to totally prevent the morphological alterations and cytoskeletal reorganization induced by Val, indicating that the RhoA signaling pathway was involved in these effects. 4. Furthermore, creatine attenuated the morphological alterations provoked by the BCAA, the protection being more pronounced for Val, suggesting that impairment of energy homeostasis is partially involved in BCAA cytotoxic action. The data indicate that the BCAA accumulating in MSUD are toxic to astrocyte cells, a fact that may be related to the pathogenesis of the neurological dysfunction of MSUD patients.

show abstract

Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation

Cited by 70 publications

References 27 publications

Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivomodel of Alzheimer’s disease

Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivomodel of Alzheimer’s disease

Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function

Morphological Alterations and Cell Death Provoked by the Branched-Chain α-Amino Acids Accumulating in Maple Syrup Urine Disease in Astrocytes from Rat Cerebral Cortex

Contact Info

Product

Resources

About