Resistance of the dentate gyrus to induced apoptosis during ageing is associated with increases in transforming growth factor-β1 messenger RNA

Bye, Nicole; Zieba, Malgorzata; Wreford, Nigel G.; Nichols, Nancy R.

doi:10.1016/s0306-4522(01)00236-6

Cited by 37 publications

(28 citation statements)

References 46 publications

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“…We found that there is increased TGFβ signaling in the aged brain in the absence of injury and this may be part of an anti-inflammatory strategy employed by the aging brain to counter the primed pro-inflammatory state. Our findings are consistent with others who have shown that in aging the expression of TGFβ receptors increases, as does the expression of TGF-β1 [2,20,36,37]. Conversely, since the data we present here strongly suggests that TGFβ signaling is important for neuronal function, increased TGFβ signaling in the aged brain may be required to maintain normal neuronal function in the face of age related changes.…”

Section: Discussionsupporting

confidence: 93%

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

Doyle

Cekanaviciute

Mamer

et al. 2010

J Neuroinflammation

216

166

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BackgroundTGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging.MethodsWe performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.ResultsTGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes.ConclusionsWe found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

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Section: Discussionsupporting

confidence: 93%

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

Doyle

Cekanaviciute

Mamer

et al. 2010

J Neuroinflammation

216

166

View full text Add to dashboard Cite

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“…To assess BDNF mRNA expression, silver grains clustered over cresyl violet stained cells were analyzed by computerassisted grain counting (Morgan et al, 1993;Bye et al, 2001). Granule neurons and pyramidal neurons in a designated portion of five hippocampal subregions including DG (160 cells per rat), CA1 (70 cells per rat), CA2 (30 cells per rat), and CA3 (70 cells per rat) were individually assessed (330 cells total per rat).…”

Section: Bdnf In Situ Hybridization Data Analysismentioning

confidence: 99%

Combined neonatal stress and young‐adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: Effects on learning and memory

et al. 2008

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Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats. To assess whether there were behavioral effects, which may correlate with the BDNF changes, learning and memory was tested in the Y-maze test for short term spatial memory, the Morris water maze for long-term spatial memory, and the T-maze test for working memory. Four groups of rats received either no stress, maternal deprivation, corticosterone treatment, or both. Dorsal hippocampus sections obtained from parallel groups were used for BDNF mRNA in situ hybridization. Rats which had undergone both maternal deprivation and corticosterone treatment displayed a unique and significant 25-35% reduction of BDNF expression in the dentate gyrus (DG), and similar trends in the CA1 and CA3 regions of the hippocampus. These "two-hit" animals exhibited a learning delay in the Morris water maze test, a marked deficit in the Y-maze, but little change in the T-maze test. However, some aspects of cognition were also altered in rats with either maternal deprivation or corticosterone treatment. This study demonstrates a persistent effect of two developmental disruptions on BDNF expression in the hippocampus, with parallel, but not completely correlative changes in learning and memory.

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“…However, the increased expression of this growth factor in pathological conditions of neurodegenerative diseases, acute trauma, and neuro-inflammation and ageing has been demonstrated (Bye et al 2001). Acute damage to the brain and hypoxic/ ischemic lesions increase neurogenesis in SVZ and HC and can lead to the migration of the newborn cells toward the lesioned area (Arvidsson et al 2002;Parent et al 2002;Jin et al 2006).…”

Section: Tgf-beta1 As a Cytostatic Factor Of Neural Stem Cells And Inmentioning

confidence: 99%

TGF-beta in neural stem cells and in tumors of the central nervous system

Aigner

Bogdahn

2007

Cell Tissue Res

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Mechanisms that regulate neural stem cell activity in the adult brain are tightly coordinated. They provide new neurons and glia in regions associated with high cellular and functional plasticity, after injury, or during neurodegeneration. Because of the proliferative and plastic potential of neural stem cells, they are currently thought to escape their physiological control mechanisms and transform to cancer stem cells. Signals provided by proteins of the transforming growth factor (TGF)-beta family might represent a system by which neural stem cells are controlled under physiological conditions but released from this control after transformation to cancer stem cells. TGF-beta is a multifunctional cytokine involved in various physiological and patho-physiological processes of the brain. It is induced in the adult brain after injury or hypoxia and during neurodegeneration when it modulates and dampens inflammatory responses. After injury, although TGF-beta is neuroprotective, it may limit the self-repair of the brain by inhibiting neural stem cell proliferation. Similar to its effect on neural stem cells, TGF-beta reveals anti-proliferative control on most cell types; however, paradoxically, many brain tumors escape from TGF-beta control. Moreover, brain tumors develop mechanisms that change the anti-proliferative influence of TGF-beta into oncogenic cues, mainly by orchestrating a multitude of TGF-beta-mediated effects upon matrix, migration and invasion, angiogenesis, and, most importantly, immune escape mechanisms. Thus, TGF-beta is involved in tumor progression. This review focuses on TGF-beta and its role in the regulation and control of neural and of brain-cancer stem cells.

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Resistance of the dentate gyrus to induced apoptosis during ageing is associated with increases in transforming growth factor-β1 messenger RNA

Cited by 37 publications

References 46 publications

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

Combined neonatal stress and young‐adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: Effects on learning and memory

TGF-beta in neural stem cells and in tumors of the central nervous system

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