The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1) increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.

Related collections

Most cited references 41

Record: found
Abstract: found
Article: not found

Control of microglial neurotoxicity by the fractalkine receptor.

Astrid E. Cardona, Erik P Pioro, Margaret E Sasse … (2006)

Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

0 comments Cited 472 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Long-term potentiation and memory.

M A Lynch (2004)

One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

0 comments Cited 439 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.

Christopher B Davis, J Raingeaud, Chris Dickens … (1995)

Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.

0 comments Cited 436 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2012

Publication date (Electronic): 18 September 2012

Volume: 7

Issue: 9

Electronic Location Identifier: e45250

Affiliations

[1 ]Department of Pharmacology, University of Florence, Florence, Italy

[2 ]Department of Anatomy, Histology and Legal Medicine, University of Florence, Florence, Italy

[3 ]Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria

[4 ]Department of Psychology, The Ohio State University, Columbus, Ohio, United States of America

Univ. Kentucky, United States of America

Author notes

* E-mail: mariagrazia.giovannini@ 123456unifi.it

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: MGG FC GLW SZ. Performed the experiments: FC DL DN HMB MGG PP-K. Analyzed the data: MGG FC DL GLW HMB PP-K. Contributed reagents/materials/analysis tools: DL FC DN. Wrote the paper: MGG GLW SZ DL. Made confocal analyses: DN DL MGG.

Article

Publisher ID: PONE-D-12-18826

DOI: 10.1371/journal.pone.0045250

PMC ID: 3445467

PubMed ID: 23028880

SO-VID: a6c6773f-2bdf-4a31-acaf-c047f65310e1

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 26 June 2012

Date accepted : 16 August 2012

Page count

Pages: 19

Funding

The project was partly funded by Banco S. Paolo (Grant 2008.1282), PRIN 40% (2007), Università di Firenze (ex 60%). PP-K was recipient of a CNR-BAN Grant (2010–2012). GLW and HMB were supported by the United States Public Health Service, RO1 AG030331 and AG037320. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus

Read this article at

Abstract

Related collections

PLOS Climate

Most cited references 41

Control of microglial neurotoxicity by the fractalkine receptor.

Long-term potentiation and memory.

Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 70

Cited by 106

Most referenced authors 649