Gene expression in activated brain microglia: identification of a proteinase inhibitor that increases microglial cell number

Thakker‐Varia, Smita; Elkabes, Stella; Schick, Charles; Silverman, Gary A.; Peng, Lang; Sherwood, Ann C.; Black, Ira B.

doi:10.1016/s0169-328x(98)00034-5

Cited by 5 publications

(8 citation statements)

References 26 publications

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“…Moreover, in a separate study using DNA microarrays, Rab3A levels were increased by BDNF treatment (Thakker-Varia et al, 2000). Taken together, these findings validate the differential screening approach by isolation of at least two genes (Rab3A and GC) potentially relevant to BDNF-induced synaptic plasticity (Thakker-Varia et al, 1998).…”

Section: Bdnf Regulates Gene Expression At 3 Hrsupporting

confidence: 71%

“…R NA isolation. Total cellular RNA was prepared from virtually pure neuronal cultures treated with either BDN F or NGF (50 ng /ml) or vehicle (water) for 3 hr by the guanidine isothiocyanate method (Thakker-Varia et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

“…mR NA differential display. Display was performed essentially as described previously (Thakker-Varia et al, 1998) using the RNA image kit as per instructions (Gene Hunter, Boston, M A). Radiolabeled PCR products were analyzed by denaturing 6% PAGE.…”

Section: Methodsmentioning

confidence: 99%

“…Band recover y, cloning, and DNA sequencing. DNA from putative differentially expressed bands found in duplicate samples was reamplified by PCR using the appropriate primer combination for 40 cycles (Thakker-Varia et al, 1998). cDNA fragments were cloned into pCR II using the TA cloning kit (Invitrogen, C arlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

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Rab3A Is Required for Brain-Derived Neurotrophic Factor-Induced Synaptic Plasticity: Transcriptional Analysis at the Population and Single-Cell Levels

et al. 2001

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Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in hippocampal neurons, in addition to promoting survival and differentiation. To identify genes involved in trophic regulation of synaptic plasticity, we have used a multidisciplinary approach of differential display and family-specific slot blots in combination with whole-cell patch-clamp recordings of dissociated hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in synaptic charge and a concomitant induction of 11 genes as revealed by differential display, including the small GTP-binding vesicular trafficking protein Rab3A and the enzyme guanylate cyclase (GC). Slot blot analysis on a population of neurons confirmed an average of 3.1-fold induction of these clones. In contrast, individual pyramidal-like neurons that were first characterized electrophysiologically in the presence of BDNF and subjected to transcriptional analysis displayed more robust increases (4.8-fold), emphasizing the neuronal heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by translational regulation, shown by Western blot analysis. Furthermore, a number of GC-associated and Rab3A effector molecules were induced by BDNF at either the gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic plasticity was assessed using cells derived from Rab3A knock-out mice. These neurons failed to show an increase in synaptic charge in response to BDNF at 10 min; however a late response to BDNF was detected at 20 min. This late response was similar in time course to that induced by postsynaptic activation of glutamate receptors. Our results demonstrate a requirement for Rab3A and may reveal a temporal distinction between presynaptic and postsynaptic mechanisms of BDNF-induced synaptic plasticity associated with learning and memory.

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Section: Bdnf Regulates Gene Expression At 3 Hrsupporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Rab3A Is Required for Brain-Derived Neurotrophic Factor-Induced Synaptic Plasticity: Transcriptional Analysis at the Population and Single-Cell Levels

et al. 2001

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“…Matrix metalloproteinase (MMP)-9, implicated in various brain injuries, has been shown to contribute to the pathogenesis of brain extravasation and edema. 13 It is of interest to note that MMP-9 can be induced by the serpin SERPINB3 14 and using reverse transcription-polymerase chain reaction (RT-PCR) differential display Thakker -Varia et al 15 have detected a remarkable increase of SERPINB3 expression in lipopolysaccharide (LPS)-activated microglial cultures. In addition, this serpin was able to increase microglial cell number.…”

Section: Introductionmentioning

confidence: 99%

Increased Th1 immune response in SERPINB3 transgenic mice during acute liver failure

Villano

Lunardi

Turato

et al. 2012

Exp Biol Med (Maywood)

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Acute liver failure (ALF) is characterized by severe neurological complications, known as acute hepatic encephalopathy, where brain ammonia and inflammatory processes play a dominant role. In experimental models of acute liver failure SERPINB3 was found significantly increased in microglia, the intrinsic immune cells of the central nervous system. The aim of the present study was to investigate the extent of brain tissue damage and the inflammatory milieu in experimental acute liver failure using a SERPINB3-transgenic mouse model. C57BL/6J wild-type and transgenic mice were inoculated with acetaminophen or phosphate-buffered saline and sacrificed 20 h postinjection. Proliferation and apoptotic activity were analyzed in brain tissue by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique. The expression of cytokines was analysed in brain and liver tissue by real time polymerase chain reaction and in the corresponding serum samples using a Bio-Plex system. Acetaminophen induced a significantly lower body temperature and shorter survival in transgenic than in wild-type mice, despite liver function was similar in both groups. The brain of transgenic mice, expressing SERPINB3 positivity in microglia, showed increased glial cell number, associated to significant lower apoptotic death events, compared with wild-type mice. In mice injected with acetaminophen, remarkably higher values of cytokines mRNA were observed in the liver of both groups, with a trend toward higher values in transgenic animals. In brain tissue similar increase of tumor necrosis factor-α was detected in transgenic and wild-type mice, while IL-10 mRNA increased only in the wild-type group. A remarkable increase of circulating Th1 cytokines was detected in serum of transgenic mice, while in the wild-type group they remained rather unchanged. These figures were associated with lower levels of granulocyte macropage colony-stimulating factor, despite similar increase of IL-10 values in both groups. In conclusion, in acute liver failure SERPINB3 determines an enhanced inflammatory background, mainly mediated by higher levels of Th1 proinflammatory cytokines.

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Alder

Thakker‐Varia

Black

2002

Neurochemical Research

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Gene profiling in the central nervous system presents unique challenges due to the unprecedented heterogeneity of cells, systems and functions in time and space. We have employed a multidisciplinary approach using whole cell patch clamp recording and transcriptional analysis to define the genomic basis of trophin-induced hippocampal synaptic plasticity. Transcriptional analysis of single cells by linear amplification of antisense RNA has added a new dimension of sensitivity and selectivity to the study of the complex and heterogeneous population of neurons. We describe different gene expression profiling techniques that offer novel approaches to monitoring thousands of genes in parallel, fostering identification of circuits involved in learning and memory.

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Gene expression in activated brain microglia: identification of a proteinase inhibitor that increases microglial cell number

Cited by 5 publications

References 26 publications

Rab3A Is Required for Brain-Derived Neurotrophic Factor-Induced Synaptic Plasticity: Transcriptional Analysis at the Population and Single-Cell Levels

Rab3A Is Required for Brain-Derived Neurotrophic Factor-Induced Synaptic Plasticity: Transcriptional Analysis at the Population and Single-Cell Levels

Increased Th1 immune response in SERPINB3 transgenic mice during acute liver failure

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