Central Nervous System Complications of Diabetes in Streptozotocin-Induced Diabetic Rats: A Histopathological and Immunohistochemical Examination

Abstract

Diabetes mellitus is a common, potentially serious metabolic disorder. Over the long term, diabetes leads to serious consequences in a number of tissues, especially those that are insulin insensitive (retina, neurons, kidneys). It also causes a variety of functional and structural disorders in the central and peripheral nervous systems. We investigated whether neurodegenerative changes were observable in the hippocampus, cortex, and cerebellum after 4 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of melatonin. Male Wistar rats (n = 32) were divided into four groups (n = 8 each): untreated controls, melatonin-treated controls, untreated diabetics, and melatonin-treated diabetics. Experimental diabetes was induced by a single dose of STZ (60 mg/kg, intraperitoneal (ip)). For 3 days before the administration of STZ, melatonin (200 microg/kg/day, ip) was injected and continued for 4 weeks. Sections of hippocampus, cortex, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, brain tissues were examined immunohistochemically for the expression of glial and neuronal markers, including glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and heat shock protein-70 (HSP-70). No neurodegenerative changes were observed in the hippocampus, cortex, or cerebellum of the untreated diabetic group after 4 weeks compared with the other groups. We did not observe any change in GFAP, NSE, or HSP-70 immunostaining in the brain tissues of STZ-induced diabetic rats. In summary, after 4 weeks of STZ-induced diabetes in rats, no degenerative or immunohistochemical changes were detected in the hippocampus, cortex, or cerebellum.

Analysis of diabetes-related cerebellar changes in streptozotocin-induced diabetic rats

“…The cerebellar cortex was susceptible to hyperglycemia-induced oxidative stress, which contributed to the neuronal damage and increased astrocyte activity (8). Immunohistochemical studies that evaluated the effects of STZ-induced diabetes on the nervous system of rats with 6 weeks or longer duration of diabetes have shown significant increases in the GFAP and S-100b constituents in diabetics compared to nondiabetic controls (1). Diabetes was shown to cause increased glial activity and the mechanism was thought to be elevated oxidative stress, whereas these histopathological and immunohistochemical changes could not be observed in STZ-induced diabetic rats after 4 weeks (1).…”

“…However, all these studies are not specific to the cerebellum. Research studies related to the cerebellum are very few to our knowledge (1,2,4,7,8).…”

Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

“…Cognitive and behavioral dysfunctions are being the most apparent CNS impairments reported in both humans (Petrofsky et al, 2005; Kodl and Seaquist, 2008) and animal models of diabetes (Biessels et al, 1994; Coleman et al, 2004; Guven et al, 2009). It is held that altered metabolism of lipids, proteins and carbohydrates following diabetes leads to oxidative stress and cell death in the brain, causing a state of dysfunctions in cognition and behavior.…”

Cardiovascular Autonomic Dysfunction in Diabetes as a Complication: Cellular and Molecular Mechanisms

“…Although many studies have shown that diabetes causes a variety of functional and morphological disorders in the central nervous system (including hippocampus, cortex, and cerebellum) (Biessels et al, 1999;Selvarajah & Tesfaye, 2006;Mooradian, 1997a;Mooradian, 1997b;Guven et al, 2009), the role of the central neural component in the blunted arterial baroreflex in type 1 diabetes is less well documented. One recent study from Gu, et al (Gu et al, 2008) suggests that a deficit of the central neural component contributes to the attenuation of arterial baroreflex in OVE26 type 1 diabetic mice.…”