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Postnatal development of rat dentate gyrus: effects of methylazoxymethanol administration
Sandra Ciaroni1, Tiziana Cecchini, Paola Ferri
1Institute of Morphological Sciences, University of Urbino, loc. Crocicchia, I-61029 (PS), Urbino, Italy. s.ciaroni@uniurb.it
Abstract:
In order to investigate the role of postnatal neurogenesis in granule cell number control in the rat dentate gyrus, we administered Methylazoxymethanol (MAM), a drug able to prevent cells from dividing, on P3, P5, P7, P9, when the most granule cells are produced. The effect of MAM on the number of proliferating precursors and of granule cells was examined at P16 and P90. We used 5-bromo-2'-deoxyuridine administration to label proliferating cells and immunohistochemistry to characterize the cell phenotype using neuron markers TUC 4, PSA-NCAM, Calbindin D28K and glial marker GFAP. At 16 days of age in MAM-treated rats we observed a significant decrease of BrdU-positive cells. Consistently, a decrease in density and number of granule cells was found compared to the controls. At 90 days the dentate gyrus of treated rats showed a complete recovery: no differences in the density, total number of neurons, the BrdU- and TUC 4-positive cells were revealed with respect to the controls. No deficits were evident in performance on the water maze in MAM-treated rats. These data suggest that the dentate gyrus is able to re-establish the proliferative zone and to rebuild the granule cell layer following neonatal MAM administration.
Insights
Neonatal administration of Methylazoxymethanol (MAM) temporarily reduces granule cell numbers in the rat dentate gyrus. However, the brain demonstrates remarkable recovery, with normal cell counts and function by adulthood.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Postnatal neurogenesis is crucial for establishing neuronal populations.
- The dentate gyrus, a key brain region for learning and memory, undergoes significant granule cell production after birth.
- Understanding the plasticity of neurogenesis is vital for comprehending brain development and recovery.
Purpose of the Study:
- To investigate the impact of inhibiting cell division during peak postnatal neurogenesis on dentate gyrus granule cell numbers.
- To assess the long-term effects of neonatal neurogenesis disruption on dentate gyrus structure and function.
- To determine the regenerative capacity of the dentate gyrus following early-life cell proliferation blockade.
Main Methods:
- Administration of Methylazoxymethanol (MAM) on postnatal days 3, 5, 7, and 9 to inhibit cell proliferation.
- Labeling of proliferating cells using 5-bromo-2'-deoxyuridine (BrdU) and analysis at postnatal days 16 and 90.
- Immunohistochemistry using neuronal and glial markers (TUC 4, PSA-NCAM, Calbindin D28K, GFAP) to characterize cell phenotypes.
- Assessment of granule cell density, number, and performance in the water maze task.
Main Results:
- MAM treatment significantly reduced BrdU-positive cells and granule cell numbers at postnatal day 16.
- By postnatal day 90, dentate gyrus structure (density, neuron count) and cell proliferation markers (BrdU, TUC 4) fully recovered in MAM-treated rats compared to controls.
- No significant differences in water maze performance were observed between MAM-treated and control rats at maturity.
Conclusions:
- Neonatal inhibition of cell division in the dentate gyrus leads to transient granule cell loss but does not cause permanent deficits.
- The dentate gyrus exhibits significant plasticity, capable of restoring its proliferative capacity and rebuilding the granule cell layer.
- These findings highlight the brain's resilience and ability to compensate for early-life disruptions in neurogenesis.