TGF-β1 mRNA Increases in Macrophage/Microglial Cells of the Hippocampus in Response to Deafferentation and Kainic Acid-Induced Neurodegeneration

Morgan, Todd E.; Nichols, Nancy R.; Pasinetti, Giulio Maria; Finch, Caleb E.

doi:10.1006/exnr.1993.1063

Cited by 165 publications

(71 citation statements)

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“…In the CNS, TGF␤1 has been shown to promote the survival of embryonic, neonatal, and adult neurons (Martinou et al, 1990;Oppenheim et al, 1993;Boche et al, 2003;Schober et al, 2007), assist in neurite outgrowth (Ishihara et al, 1994;Abe et al, 1996), protect against experimental allergic encephalomyelitis (Racke et al, 1991;Johns and Sriram, 1993;Santambrogio et al, 1993), and inhibit microglial and astrocyte pro-liferation (Lindholm et al, 1992;Vergeli et al, 1995). Studies using ramified microglia grown on an astrocyte monolayer also demonstrated the strong inhibitory effect of TGF␤1 on microglial proliferation (Jones et al, 1998), agreeing with reports in vivo that suggest that TGF␤1 is responsible for the downregulation of the microglial response after injury (Kiefer et al, 1993a;Morgan et al, 1993).…”

Section: Introductionsupporting

confidence: 69%

Endogenous Transforming Growth Factor β1 Suppresses Inflammation and Promotes Survival in Adult CNS

Makwana¹,

Jones²,

Cuthill³

et al. 2007

J. Neurosci.

103

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Transforming growth factor ␤1 (TGF␤1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that is upregulated after injury, but also expressed in the normal nervous system. In the current study, we examined the regulation of TGF␤1 and the effects of TGF␤1 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGF␤1-deficient mice, this study was performed on a T-and B-cell-deficient RAG2Ϫ/Ϫ background. Compared with wild-type siblings, homozygous deletion of TGF␤1 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [␣X␤2, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGF␤1 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), ␣6␤1, and ␣M␤2] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGF␤1 also caused an ϳ10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain.

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Section: Introductionsupporting

confidence: 69%

Endogenous Transforming Growth Factor β1 Suppresses Inflammation and Promotes Survival in Adult CNS

Makwana¹,

Jones²,

Cuthill³

et al. 2007

J. Neurosci.

103

View full text Add to dashboard Cite

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“…Most previous studies examined the cell type of TGF-β expression following some type of induction. TGF-β1 upregulation in astrocytes and microglia has been reported to be a predominant response to lesion and during pathology (Krohn, 1999;Wu et al, 2007;Wu et al, 2008) that results in the induction of reactive phenotypes (Flanders et al, 1998;Morgan et al, 1993). Under basal conditions, astrocytes were also shown to express TGF-β1 in the preoptic area (Bouret et al, 2004;Dhandapani & Brann, 2003).…”

Section: Distribution Of Tgf-βs Their Binding Proteins and Receptorsmentioning

confidence: 99%

“…Apart from ischemia, trauma, or tumors, deafferentation and neurodegeneration also induce TGF-β expression in the central nervous system (Morgan et al, 1993). Therefore, it is not surprising that TGF-βs were implicated in a variety of neurodegenerative diseases.…”

Section: Neuroprotective Function In Additional Neurological Diseasesmentioning

confidence: 99%

Transforming Growth Factor Beta in the Central Nervous System

Dobolyi¹

2012

Neuroscience - Dealing With Frontiers

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“…This review emphasizes TGF-p1, because its activities during responses to brain injury are better understood than those of TGF-p2 and 433. For most information cited without references, see general reviews and recent papers Roberts and Sporn, 1990;da Cunha et al, 1993;Morgan et al, 1993;Pasinetti et al, 19931. bridization [da Cunha et al, 1993;Nichols and Finch, 1991;Unsicker et al, 19911. At a cellular level, the meninges and choroid plexus of normal rodent and human brains clearly contain both TGF-p1 mRNA and protein.…”

Section: Introductionmentioning

confidence: 99%

TGF‐β1 is an organizer of responses to neurodgeneration

Finch

Laping

Morgan

et al. 1993

J of Cellular Biochemistry

191

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TGF-PI mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF-PI mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF-PI mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF-PI protein observed in PAiamyloid-containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims.Involvement of TGF-01 in these human brain disorders is discussed in relation to the potent effects of TGF-PI on wound healing and inflammatory responses in peripheral tissues.We hypothesize that TGF-PI and possibly other TGF-P peptides have organizing roles in responses to neurodegeneration and brain injury that are similar to those observed in non-neural tissues. Work from many laboratories has shown that activities of TGF-P peptides on brain cells include chemotaxis, modification of extracellular matrix, and regulation of cytoskeletal gene expression and of neurotrophins. Similar activities of the TGF-P's are well established in other tissues.

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TGF-β1 mRNA Increases in Macrophage/Microglial Cells of the Hippocampus in Response to Deafferentation and Kainic Acid-Induced Neurodegeneration

Cited by 165 publications

References 0 publications

Endogenous Transforming Growth Factor β1 Suppresses Inflammation and Promotes Survival in Adult CNS

Endogenous Transforming Growth Factor β1 Suppresses Inflammation and Promotes Survival in Adult CNS

Transforming Growth Factor Beta in the Central Nervous System

TGF‐β1 is an organizer of responses to neurodgeneration

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