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Prolonged lead exposure modifies astrocyte cytoskeletal proteins in the rat brain
A Selvín-Testa1, C F Loidl, E M López
1Instituto de Biología Celular y Neurociencias, School of Medicine, University of Buenos Aires, R. Argentina.
Insights
Chronic lead exposure in rats alters astrocyte responses, leading to changes in glial fibrillar acidic protein (GFAP) and vimentin expression. These alterations suggest accelerated aging in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Lead exposure is a significant neurotoxicant with long-term effects on the central nervous system (CNS).
- Astrocyte reactivity is a key indicator of CNS injury and response to toxicants.
- Understanding the temporal and regional astrocyte response to lead is crucial for assessing neurodevelopmental and neurodegenerative risks.
Purpose of the Study:
- To investigate the time-course and regional astrocyte responses to prolonged lead exposure in developing rats.
- To evaluate the expression of glial fibrillar acidic protein (GFAP) and vimentin as markers of astrocyte activation.
- To determine if lead exposure accelerates age-dependent changes in the CNS.
Main Methods:
- Rat pups were exposed to lead acetate via maternal milk from postnatal days 1 (P1) and 7 (P7).
- Lead exposure continued post-weaning for up to 15 months.
- Immunohistochemistry for GFAP and vimentin was used to assess astrocyte responses in hippocampal and cerebellar tissues.
Main Results:
- A transient increase in GFAP immunoreactivity was observed in hippocampal and cerebellar astrocytes within 2-3 months.
- After 4-12 months, GFAP levels returned to near control levels despite persistent high blood lead levels, with lipofuscin-like bodies appearing in neuronal and glial cells.
- After one year, increased GFAP reactivity and vimentin-positive cells were detected in the fascia dentata and cerebral cortex, with vimentin+ cells showing a smaller, restricted arrangement. Cerebellar vimentin+ astrocyte hypertrophy was confined to the white matter.
Conclusions:
- Prolonged lead exposure induces significant, long-lasting alterations in astrocyte morphology and protein expression (GFAP, vimentin).
- The appearance of lipofuscin-like bodies and altered astrocyte markers suggest modifications to the neuronal microenvironment.
- These lead-induced changes may accelerate age-dependent alterations in the CNS, highlighting potential long-term neurotoxic effects.
Abstract:
The time-course and the regional astrocyte responses were studied during 15 months of continuous lead-exposure. Rat pups were exposed from postnatal day 1 (P1 group) and day 7 (P7 group) through the maternal milk, (1g% lead acetate solution in the drinking water). Following weaning lead-exposed offspring were treated during 15 months. Immunohistochemical staining for glial fibrillar acidic protein (GFAP) and vimentin were used to evaluate astrocyte response. In coincidence with previous results, after 2-3 months of treatment, we observed in both groups a transient increase of GFAP immunoreactivity in hippocampal and cerebellar astrocytes (first stage). After 4-12 months (second stage), the hypertrophy declined to near control levels despite the persistence of high blood lead-levels; meanwhile, lipofuscin-like bodies appeared in neuronal and glial cells. After one year of treatment, the immunostaining of homologous sections showed an increase of GFAP reactivity and the presence of vimentin + cells in the upper and the lower limb, and in the hilus of the fascia dentata. GFAP and vimentin astrocytic response extended to the adjacent cerebral cortex after 14 months. Although both cells showed a similar aspect, vimentin + cells showed a smaller area and a restricted arrangement. However, in the cerebellum the hypertrophy of vimentin positive astrocyte and Bergmann fibers was confined to the white matter as observed in the first stage. Astrocyte alterations, the recovery of vimentin expression and the appearance of lipofuscin-like bodies induced by prolonged lead-exposure suggest modifications in neuronal microenvironment, and might accelerate age-dependent changes in CNS.