Cellular and Histomorphometric Study of Hippocampal Damage in Diabetes Mellitus

Thursday, 15 July 2010

Sergio Márquez-Gamiño, MD, PhD
Departamento de Ciencias Aplicadas al Trabajo. División de Ciencias de la Salud, Universidad de Guanajuato Campus León, León, Guanajuato, Mexico
Karla S. Vera-Delgado, RN, MSc
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Mexico
Cipriana Caudillo-Cisneros, RN, MS
Departamento de Enfermeria y Obstetricia de Leon, Universidad de Guanajuato Campus Leon, Leon, Guanajuato, Mexico

Learning Objective 1: To know the morphological hippocampal changes induced by diabetes mellitus in an experimental model.

Learning Objective 2: To learn about cellular alterations occurring in the brain during diabetes mellitus.

Purpose: Diabetes mellitus (DM) has become an important worldwide health problem. In human beings it has been associated to cognitive alterations, as well as to vascular dementia and Alzheimer disease increased risk. Peripheral neuropathy is the complication most frequently studied. However, the central nervous system is also phenotypically affected by DM. The underlying mechanisms have not been elucidated. Our aim was to evaluate the hippocampal pyramidal neurons cellularity and the structural modifications in the CA1, CA2, CA3 and CA4 regions of a diabetic experimental model.  
  Methods: Three weeks old Wistar male rats were randomly distributed in two groups: diabetics and control. Experimental DM was streptozotocine-induced. Weight and blood glucose were tested prior and 24 h following diabetes induction. Animals were considered diabetic when blood glucose was >250 mg/dl. Under pentobarbital (60 mg/kg) anesthesia brain tissue was fixed by 10% formaldehyde intracardiac perfusion. 3 mm-thick hippocampal slices were obtained and hematoxylin-eosin stained to be evaluated under 40 and 100X objectives, dry and oil immersion respectively. Image-Pro 6.1 digital images were saved for analysis.

Results: Qualitative modifications including axonal disruption, plasmatic membrane disorganization, cell body morphology alterations, dendrites shortening, as well as interneuronal spatial-relation changes were documented. Quantitatively, reduced cellularity was observed in CA2 and CA3, while an increased number of neural cells in CA1 and dentate gyrus was seen. Also a 12% reduction in the CA2 pyramidal cell bodies was found. Conclusion: The cell and hippocampal tissue modifications observed under diabetic conditions are important, and could be responsible for the deteriorated brain superior functions observed in diabetic patients, particularly for memory loss and learning disability.