Academic journal article Cognitie, Creier, Comportament

Chronic Intrahippocampal Administration of Streptozotocin Targeting Insulin Receptors Induced Memory Loss in Rats: A Dose Comparison Study

Academic journal article Cognitie, Creier, Comportament

Chronic Intrahippocampal Administration of Streptozotocin Targeting Insulin Receptors Induced Memory Loss in Rats: A Dose Comparison Study

Article excerpt

Alzheimer's disease (AD) is a slow degenerative brain disorder that causes memory loss and other cognitive impairments (Santos, Mazucanti, Xavier, & Torräo, 2012). The gradual loss of memory is primarily due to deposits of senile plaques and formation of neurofibrillary tangles (Karantzoulis & Galvin, 2011). Most of the AD cases reported worldwide are sporadic AD (99%) and the remaining 1% known as familial AD (Chen et al., 2012; Singh & Kumar, 2016). To date there is still no cure for AD. Research on AD is ongoing to find ways to prevent, detect and cure the disease. To do so, researchers developed AD animal models to mimic the complexity of the disease pathology (Singh & Kumar, 2016). Researchers have reported various AD models using mice and rats such as transgenic mice (Latta et al., 2015), intracerebroventricular (ICV) administration of amyloid beta (Cetin, Yazihan, Dincer, & Akbulut, 2012; Zussy et al., 2013), streptozotocin (STZ) (Knezovic et al., 2015; Liu et al., 2014; Salkovic-Petrisic et al., 2011) and lipopolysaccharide (Kitazawa, Oddo, Yamasaki, Green, & LaFerla, 2015), and intrahippocampal (IH) administration of amyloid beta (Malin et al., 2001; Singh & Kumar, 2016). These AD models have shown their own advantages and disadvantages. The STZ-ICV AD model is a popular and appropriate experimental model for researchers to study AD since this model highly resembles many features that are common with sporadic AD in humans (Kamat, 2015), such as clearance of neuroinflammation, neurobehavioral, oxidative stress and biochemical alterations (Singh & Kumar, 2016). However, the cerebral amyloid angiopathy was not observed less than 3 months after STZ administration (Salkovic-Petrisic et al., 2011).

STZ is a glucosamine-nitrosourea compound that is known to be toxic to beta cells of the pancreas and transported through glucose transporter-2. This compound is commonly used to produce diabetes in animals. STZ injected intravenously was able to destroy the beta cells within 4 days (Akbarzadeh et al., 2007). Prolonged treatment of STZ in male Wistar rats up to 24 weeks showed chronic effects of diabetes such as cataracts, impaired kidney functioning, diabetic neuropathy, heart disease and stroke (Wei et al., 2003). Eight-months old diabetic rats showed presence of ß-amyloid (Aß) and phospho-т accumulation which were associated with neurite degeneration and neuronal loss (Li, Zhang, & Sima, 2007). The extreme neuroinflammation, oxidative stress, and biochemical changes shown in STZ rodent model is considered the crucial early signs in neurodegenerative disease. Administration of STZ through ICV or intraperitoneal injection was able to produce cognitive impairment and to induce the presence of cerebral aggregated Aß fragments, total tau protein, and Aß deposits (Dou, Chen, Dufour, Alkon, & Zhao, 2005; Grünblatt, Salkovic-Petrisic, Osmanovic, Riederer, & Hoyert, 2007).

A recent study found that injection of STZ in the brain of animals which can develop insulin resistant diabetes was associated with memory impairment, progressive cholinergic deficits, glucose hypometabolism, oxidative stress and neurodegeneration that correlates with the recent finding of sporadic AD being recognized with insulin resistant brains state (Kamat, 2015). Interestingly, the insulin can modify synaptic plasticity, learning or memory, and disturbances of insulin pathways in the brain were associated with AD type symptoms and brain aging. Dou and colleagues (2005) proposed that the presence of insulin receptor (IR) in brain is mostly abundant in the hippocampus and IR plays a functional role in cognition (Grünblatt et al., 2007). Meanwhile, deregulation of brain IR was linked to age-related neurodegenerative disorders (Frolich et al., 1998). Agrawal, Tyagi, Shukla and Nath (2011) proposed that decreases in IR and insulin receptor substrate-1 (IRS-1/Akt) pathway in the Cornu Ammonis 3 (CA3) region of the hippocampus were associated with memory deficit (Agrawal et al. …

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