Astrocyte Function in Cerebral Cortex Development
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Questions and Answers

At what age did the loss of HMGB1 in astrocytes not affect its production by neurons or pericytes?

  • P21
  • P14 (correct)
  • P5
  • P7

    • Astrocyte cell density and surface ratio were significantly altered in the cerebral cortex of Hmgb1ΔAstro mice.

    False

    What is the primary role of astrocytes in relation to blood vessels during cortical expansion?

    Astrocytes position their cell bodies farther from blood vessels and send extensions back towards them.

    The distribution of the gap junction protein ______ was significantly altered in the cerebral cortex of Hmgb1ΔAstro mice.

    <p>connexin43</p> Signup and view all the answers

    Match the following ages with their corresponding astrocyte characteristics:

    <p>P4 = Peak proliferation of astrocytes P5 = Endfoot placement begins P7 = Astrocyte extensions grow towards vessels P21 = Random orientation of astrocyte extensions</p> Signup and view all the answers

    What is one of HMGB1's functions in pathological conditions in the adult brain?

    <p>Promotion of reparative angiogenesis</p> Signup and view all the answers

    What effect did the ablation of astroglial Hmgb1 have on vessel density and branching?

    <p>No effect on density and branching</p> Signup and view all the answers

    HMGB1 is only expressed during pathological conditions in the adult brain.

    <p>False</p> Signup and view all the answers

    The orientation of astrocyte extensions alongside vessels became more vertical by P21.

    <p>False</p> Signup and view all the answers

    What gene is associated with cytoskeletal regulation that shows increased methylation due to nuclear HMGB1 overexpression in astrocytes?

    <p>SASH1</p> Signup and view all the answers

    What significant change in astrocyte behavior was observed between P5 and P14?

    <p>There was a sharp increase in EGFP immunoreactivity on vessels, indicating a period of endfoot placement.</p> Signup and view all the answers

    In astrocytes, Cx43 is the most abundant __________ involved in extensive coupling between cells.

    <p>connexin</p> Signup and view all the answers

    Match the following functions of HMGB1 to their respective conditions:

    <p>Upregulation and secretion = Pathological conditions in the adult brain Decreased expression = Healthy brain at birth Active release = Stressed cells Passive release = Necrotic cell death</p> Signup and view all the answers

    During which stage of life is HMGB1 gene highly expressed according to the study?

    <p>In the newborn stage</p> Signup and view all the answers

    Astrocyte differentiation is characterized by the expression of Cx43.

    <p>True</p> Signup and view all the answers

    What behavior was observed in mutant mice compared to littermate controls during the novel object recognition test?

    <p>Travelled more distance</p> Signup and view all the answers

    Protein levels of AQP4 were significantly lower in P50 mutant mice compared to age-matched controls.

    <p>False</p> Signup and view all the answers

    What is the proposed relationship between increased production of HMGB1 under pathological conditions and neurodevelopment?

    <p>It relates to the induction of a developmental genetic program promoting growth and repair.</p> Signup and view all the answers

    What suggests an anxiety-like phenotype in mutant mice?

    <p>More entries in closed arms of the elevated plus maze test.</p> Signup and view all the answers

    Astrogliosis was found in either control or mutant mice at P50 as assessed by low _____ levels.

    <p>GFAP</p> Signup and view all the answers

    Match the following proteins to their respective descriptions:

    <p>Cx43 = Protein levels lower in mutant mice AQP4 = Slightly higher levels in P50 mutant mice GFAP = Indicator of astrogliosis HMGB1 = Highly expressed in astrocytes around birth</p> Signup and view all the answers

    What does the data suggest regarding the behavior of mutant mice during the open field test?

    <p>Increased distance traveled</p> Signup and view all the answers

    The expression of HMGB1 was lowest at P5 based on immunoreactivity in the cerebral cortex.

    <p>False</p> Signup and view all the answers

    What statistical test was used to assess the differences in protein levels?

    <p>One-way ANOVA and Tukey’s post-hoc test.</p> Signup and view all the answers

    What changes were observed in Hmgb1ΔAstro mice at P14?

    <p>Morphological alterations at the gliovascular unit</p> Signup and view all the answers

    Cerebrovascular growth is not influenced by the maturation of astrocytes.

    <p>False</p> Signup and view all the answers

    At what postnatal day does perivascular endfoot coverage begin to establish in the cerebral cortex?

    <p>P7</p> Signup and view all the answers

    What does the term 'Hmgb1' refer to in the context of this data?

    <p>A gene associated with astrocytes</p> Signup and view all the answers

    The levels of Cx43 increase in the presence of Hmgb1.

    <p>True</p> Signup and view all the answers

    The complexity of astrocyte morphology and transcriptome evolves alongside postnatal growth of cortical __________.

    <p>vessels</p> Signup and view all the answers

    Match the gene to its function related to astrocyte maturation:

    <p>Mapt49 = Cytoskeletal remodeling Rasgrf250 = Astrocyte arborization Gap43 = Axonal growth Hmgb1 = Regulates gliovascular interactions</p> Signup and view all the answers

    What is the control group referred to in the data?

    <p>Control Hmgb1'Astro</p> Signup and view all the answers

    Which statement is true regarding the astrocyte endfeet and the BBB?

    <p>Endfeet do not perturb the BBB based on previous studies.</p> Signup and view all the answers

    The data indicates a sample size of ____ for Control Hmgb1'Astro.

    <p>n=8</p> Signup and view all the answers

    Astrocyte morphogenesis is static and does not change after birth.

    <p>False</p> Signup and view all the answers

    Match the following parameters with their respective values:

    <p>Cx43 levels = 0.004 Hmgb1 = 1.5 Control = 0.00 Astro = 50 Pm</p> Signup and view all the answers

    Marked transcriptional changes in astrocytes are evident at postnatal day __________ as compared to other time points.

    <p>5</p> Signup and view all the answers

    What is the lowest Cx43 level reported in the data?

    <p>0.002</p> Signup and view all the answers

    What does 'Hmgb1flx/flx + Tam.' likely indicate in the context of this data?

    <p>Experimental treatment or condition involving Tamoxifen.</p> Signup and view all the answers

    The value '0.02' represents the highest level of Hmgb1 recorded.

    <p>False</p> Signup and view all the answers

    What did the study observe regarding astroglial coverage in Hmgb1ΔAstro mice at P14?

    <p>Decreased astroglial coverage compared to controls</p> Signup and view all the answers

    At P14, astrocyte endfeet were present around microvessels in Hmgb1ΔAstro mice.

    <p>False</p> Signup and view all the answers

    What are the primary astrocyte markers used in the study?

    <p>EGFP and GFAP</p> Signup and view all the answers

    The endothelial marker used in the study is __________.

    <p>CD31</p> Signup and view all the answers

    Match the following postnatal stages with their corresponding observations regarding astroglial coverage:

    <p>P0 = Perivascular astrocyte cell bodies closely associated with microvessels P5 = Initial development of astroglial endfeet P14 = Reduced astroglial coverage around microvessels P21 = Mature astrocytes interacting with vessels</p> Signup and view all the answers

    During which postnatal stage was a temporal developmental profile of astrocyte coverage observed?

    <p>P21</p> Signup and view all the answers

    The study focused on the interaction between neurons and astrocytes only.

    <p>False</p> Signup and view all the answers

    What did the analysis at the nanoscale level focus on in relation to astrocytes?

    <p>Astrocyte maturation and endfoot coverage</p> Signup and view all the answers

    Study Notes

    Astroglial Hmgb1 Regulates Postnatal Astrocyte Morphogenesis and Cerebrovascular Maturation

    • Astrocytes are crucial for brain blood vessels, essential for neuronal function, but the factors driving this postnatal association are unclear.
    • High-mobility group box 1 (Hmgb1), usually upregulated with injury and involved in adult cerebrovascular repair, is highly expressed in astrocytes at birth, then rapidly declines.
    • Ablation of Hmgb1 at birth affects astrocyte morphology and endfoot placement, alters the distribution of endfoot proteins (connexin43 and aquaporin-4), and impacts transcription related to cytoskeleton remodeling, profoundly disrupting endothelial structure.
    • Lack of astroglial Hmgb1 does not affect the blood-brain barrier or angiogenesis postnatally, but it does impair neurovascular coupling and negatively impacts mouse behavior in adulthood.
    • This highlights Hmgb1 as a critical player in postnatal gliovascular maturation.

    Postnatal Brain Development and Gliovascular Unit

    • Astrocytes and blood vessels mature intricately during the first two postnatal weeks in mice, forming the gliovascular unit.
    • Astrocyte morphology rapidly changes during this period, with primary branches sprouting from the cell body, dividing into finer processes. This process continues until a complex spongiform-like morphology is achieved.
    • Hmgb1 plays a crucial role in this process: high expression at birth, followed by a decrease as the gliovascular unit matures.
    • These changes in astrocyte morphology and gene expression are highly correlated with the development of the microvessels' complexity.

    Hmgb1 and Astrocyte Function

    • Astroglial Hmgb1 is important in regulating astrocyte morphogenesis and gliovascular maturation.
    • Removal of Hmgb1 affects the distribution of proteins like connexin43 and aquaporin-4, important components of astrocyte endfeet located around blood vessels. This alters the connections between astrocytes and blood vessels.
    • Removal of Hmgb1 doesn't disrupt the blood-brain barrier initially, but impairs neurovascular coupling and behavior in adult mice, implying sustained importance beyond the early postnatal period.
    • Hmgb1's regulation of the cytoskeleton is a key aspect of these effects, as shown by altered expression of associated genes in astrocytes lacking Hmgb1.

    Long-Term Impacts and Implications

    • The study suggests abnormalities in astrocyte function and gliovascular maturation lead to persistent issues in neurovascular coupling and cognitive behavior, especially in adulthood.
    • This highlights the critical period of the first two postnatal weeks for gliovascular development and potential vulnerabilities in this crucial period of brain development.
    • The study underscores the potential implications for neurological disorders and age-related cognitive decline.

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    Related Documents

    Astroglial Hmgb1 Regulates Postnatal Astrocyte Morphogenesis and Cerebrovascular Maturation PDF

    Description

    Test your knowledge on the role of HMGB1 in astrocytes and its impact on blood vessels during cortical expansion. This quiz covers genetic implications, cell density changes, and the effects of astrocyte ablation. Explore key concepts related to astrocyte characteristics and their functions in both healthy and pathological states.

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