Are Astrocytes Central Players in the Pathophysiology of Multiple Sclerosis?

Keyser, Jacques De; Zeinstra, Esther; Frohman, Elliot M.

doi:10.1001/archneur.60.1.132

Cited by 81 publications

(50 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The astrocytic expression of MHC class II molecules in multiple sclerosis may be a result of failure of noradrenergic suppression. This concept is consistent with the finding by the same group [48,[373][374] that white matter astrocytes in multiple sclerosis lack expression of β-adrenergic receptors (Fig. 3) and that by Frohman et al [310] that noradrenaline inhibits immune reactions by interfering with the effect of INF-γ on MHC class II expression.…”

Section: Multiple Sclerosis Canine Distemper and Eaesupporting

confidence: 91%

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Hertz¹,

Chen²,

Gibbs³

et al. 2004

CDTCNSND

View full text Add to dashboard Cite

Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodal, long-term memory, which is reinforced by β-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occurs at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

show abstract

Section: Multiple Sclerosis Canine Distemper and Eaesupporting

confidence: 91%

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Hertz¹,

Chen²,

Gibbs³

et al. 2004

CDTCNSND

View full text Add to dashboard Cite

show abstract

“…However, there are discrepancies in the literature concerning the ability of astrocytes to act as fully competent APCs (Aloisi et al, 2000a;Becher et al, 2000;Cornet et al, 2000;Cross and Ku, 2000;Dong and Benveniste, 2001;Girvin et al, 2002;Weber et al, 1994). Moreover, the demonstration of MHC-positive astrocytes in pathological human brain remains a controversial topic, even in inflammatory neurological disorders such as multiple sclerosis (MS) (De Keyser et al, 2003;Gobin et al, 2001;Traugott and Raine, 1985). In Rasmussen's encephalitis (RE), a severe inflammatory epileptic encephalopathy of childhood, expression of MHC class I molecules has been reported in astrocytes (Bauer et al, 2007;Farrell et al, 1995), suggesting an MHC class I-restricted T-cell response as a possible mechanism for the occurrence of the astrocytic degeneration observed in RE (Bauer et al, 2007).…”

Section: Astrocytes As Innate-immune-competent Cells Astrocytes As Anmentioning

confidence: 99%

Astrocyte immune responses in epilepsy

Aronica

Ravizza

Zurolo

et al. 2012

Glia

179

142

View full text Add to dashboard Cite

Astrocytes, the major glial cell type of the central nervous system (CNS), are known to play a major role in the regulation of the immune/inflammatory response in several human CNS diseases. In epilepsy-associated pathologies, the presence of astrogliosis has stimulated extensive research focused on the role of reactive astrocytes in the pathophysiological processes that underlie the development of epilepsy. In brain tissue from patients with epilepsy, astrocytes undergo significant changes in their physiological properties, including the activation of inflammatory pathways. Accumulating experimental evidence suggests that proinflammatory molecules can alter glio-neuronal communications contributing to the generation of seizures and seizure-related neuronal damage. In particular, both in vitro and in vivo data point to the role of astrocytes as both major source and target of epileptogenic inflammatory signaling. In this context, understanding the astroglial inflammatory response occurring in epileptic brain tissue may provide new strategies for targeting astrocyte-mediated epileptogenesis. This article reviews current evidence regarding the role of astrocytes in the regulation of the innate immune responses in epilepsy. Both clinical observations in drug-resistant human epilepsies and experimental findings in clinically relevant models will be discussed and elaborated, highlighting specific inflammatory pathways (such as interleukin-1b/toll-like receptor 4) that could be potential targets for antiepileptic, disease-modifying therapeutic strategies. V

show abstract

“…Astrocytes, the main glial cell type in the brain, help regulate aspects of inflammation in the CNS (reviewed in Dong & Benveniste, 2001) and may be involved in the pathogenesis of MS (reviewed in De Keyser et al, 2003). While evidence for CB 1 receptor expression by astrocytes has been found by some groups (Bouaboula et al, 1995;Sanchez et al, 1998;Moldrich & Wenger, 2000;Abood et al, 2001;Rodriguez et al, 2001;Molina-Holgado et al, 2002b;Salio et al, 2002), it has not been found by others (Sagan et al, 1999;Walter & Stella, 2003b).…”

Section: Glial Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoids and neuroinflammation

Walter

Stella

2004

British J Pharmacology

294

210

View full text Add to dashboard Cite

Growing evidence suggests that a major physiological function of the cannabinoid signaling system is to modulate neuroinflammation. This review discusses the anti-inflammatory properties of cannabinoid compounds at molecular, cellular and whole animal levels, first by examining the evidence for anti-inflammatory effects of cannabinoids obtained using in vivo animal models of clinical neuroinflammatory conditions, specifically rodent models of multiple sclerosis, and second by describing the endogenous cannabinoid (endocannabinoid) system components in immune cells. Our aim is to identify immune functions modulated by cannabinoids that could account for their antiinflammatory effects in these animal models.

show abstract

Are Astrocytes Central Players in the Pathophysiology of Multiple Sclerosis?

Cited by 81 publications

References 66 publications

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Astrocyte immune responses in epilepsy

Cannabinoids and neuroinflammation

Contact Info

Product

Resources

About