Background. Neuronal apoptosis is the major cause of diabetes central neuropathy, but its role in volumetric changes of hippocampus has not been clarified. The aims of this study were to assess the role of apoptosis in volumetric changes of dentate gyrus (DG) and CA3 region of hippocampus and to determine a reference point in which these neuropathological changes reach a meaningful level. Methods and Materials. Diabetes was induced in male Wistar rats ( ) by streptozotocin (60？mg/kg). Six weeks after diabetes, verification animals were divided into four groups as follows: diabetic treated with insulin (3–5？U), diabetic treated with vitamin C (80？mg/kg), and diabetic and control groups. At the end of 8 weeks, numerical density of apoptotic neurons and volume of dentate gyrus and CA3 were calculated by stereological methods. Results. The number of apoptotic neurons in DG and CA3 in diabetic group showed significant level of difference in comparison with the control ( ). The volume of DG and CA3 in diabetic and vitamin C showed significant level of difference compared with control ( ). Conclusion. Our results suggest that DG and CA3 volume reduction begins and progresses independently of neuronal loss. 1. Introduction Diabetes mellitus type 1 (DM1) is an endocrine disorder which is characterized by lack of insulin and hyperglycemia [1]. For a long period, it was believed that the central nervous system (CNS) as an insulin independent organ is spared from diabetic complications; however, in recent decades, studies have provided evidence that indicates the deleterious effects of DM1 on structure and functions of the brain [2–4]. Although the mechanisms through which hyperglycemia might mediate these effects are not completely understood, it seems that hyperglycemia increases oxidative stress and free radicals generation. Increased free radicals damage cellular membrane (lipid per oxidation) and initiates neuronal death signaling pathways [5, 6]. Neuronal apoptosis has been known as the main leading cause of diabetes central neuropathy. It is the common hallmark of diabetes mellitus type 1 (DM1) and neurodegenerative disorders like Alzheimer [5–7]. One of the most sensitive regions of brain to oxidative stress is the hippocampus [8]. It is a complex part of the limbic system which plays a pivotal role in cognitive functions like navigation, memory, and learning in animals and human as well. It is divided into dentate gyrus (DG) and CA1–3. Among the hippocampus subfields, DG and CA3 build an essential part of memory and learning circuits [9, 10]. The adverse
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