Neurotoxicity Research

, Volume 35, Issue 2, pp 387–400 | Cite as

Hydroxyurea Exposure and Development of the Cerebellar External Granular Layer: Effects on Granule Cell Precursors, Bergmann Glial and Microglial Cells

  • Lucía Rodríguez-Vázquez
  • Olga Vons
  • Oliver Valero
  • Joaquín MartíEmail author


The current paper presents a histological analysis of the cell death in the cerebellar external granular layer (EGL) following the treatment with a single dose (2 mg/g) of hydroxyurea (HU). The rats were examined at postnatal days (P) 5, 10, and 15, and sacrificed at appropriate times ranging from 6 to 48 h after treatment administration. Studies were done in each cortical lobe (anterior, central, posterior, and inferior). The quantification of several parameters, such as density of 5-bromo-2′-deoxyuridine, TUNEL, vimentin, and tomato lectin-stained cells, revealed that HU compromises the viability of EGL cells. Our results indicate that P10 is a time of high vulnerability to injury. We also show here that the anterior and central lobes are the cortical regions most susceptible to the action of the HU. Additionally, our data also indicate that from 6 to 24 h after HU-exposure is a time-window of high sensibility to this agent. On the other hand, our ultrastructural analysis confirmed that HU administration produces the activation of apoptotic cellular events in the EGL, resulting in a substantial number of dying cells. Different stages of apoptosis can be observed in all cortical lobes at all investigated postnatal ages and survival times. Moreover, we observed that dying neuroblasts were covered by laminar processes of Bergmann glia, and that these unipolar astrocytes presented cytological features of phagocytes engulfing apoptotic bodies and cell debris. The electron microscopy study also revealed the participation of ameboid microglial cells in the phagocytosis of apoptotic cells in the regions of the EGL with extensive cell death.


Cerebellum Hydroxyurea Apoptosis Bergmann glia cell Microglia Electron microscopy 



The authors are very grateful to Drs. María del Carmen Santa-Cruz and José Pablo Hervás for providing the animals.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Authors and Affiliations

  1. 1.Unidad de Citología e Histología, Facultad de BiocienciasUniversidad Autónoma de BarcelonaBarcelonaSpain
  2. 2.Servei d’Estadística AplicadaUniversidad Autónoma de BarcelonaBarcelonaSpain

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