Seyed Reza Pourrabie; Alireza Mohajjel Naebi
Abstract
Alzheimer's disease is a common form of progressive dementia and usually occurs between the sixth and ninth decades of life, given that there is a direct relationship between steroid hormones and neurodegenerative diseases, so the present study was designed to explore effect of testosterone in memory ...
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Alzheimer's disease is a common form of progressive dementia and usually occurs between the sixth and ninth decades of life, given that there is a direct relationship between steroid hormones and neurodegenerative diseases, so the present study was designed to explore effect of testosterone in memory impairment induced by intra-cerebroventricular (icv) injection of streptozptocin (STZ) as a model of sporadic Alzheimer disease (AD). Study was carried out on male Wistar rats. Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (3mg/kg/icv) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg/kg.d, SC), the androgen receptor antagonist flutamide (10 mg/kg.d, ip), the estrogen receptor antagonist tamoxifen (1 mg/kg.d, ip) or the aromatase inhibitor letrozole (4 mg/kg.d, ip) were administered for 6 d after the first injection of STZ. STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats.
S. R. Pourrabi1; A. R. Mohajjel Nayebi; S. E. Hossini
Volume 1, Issue 2 , November 2012, , Pages 25-32
Abstract
Steroidal sex hormones especially testosterone have a protective effect in neurodegenerative events such as Alzheimer Disease. The present study was designed to explore effect of testosterone and androgen receptors in memory impairment induced by intra- cerebroventricular (icv) injection of streptozotocin ...
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Steroidal sex hormones especially testosterone have a protective effect in neurodegenerative events such as Alzheimer Disease. The present study was designed to explore effect of testosterone and androgen receptors in memory impairment induced by intra- cerebroventricular (icv) injection of streptozotocin (STZ) as a model of sporadic AD. In this research animals were divided randomly into 11 equal groups. Experimental model of AD was induced by bilateral icv injection of STZ. STZ-induced memory impairment was assessed two weeks after the last dose of STZ by using a passive avoidance task. The interval between the placement of animals in the illuminated chamber and the entry into the dark chamber was measured as step-through latency (STL). Castration was performed by surgical removing of testis and behavioral study of memory impairment was done after 4 weeks. Results of this study showed that icv injection of STZ could induce marked (p<0.001) memory impairment. Memory was worsened in castrated rats (P<0.001) when compared with normal and sham-operated animals. Testosterone replacement therapy in 4 week castrated rats restored memory up to the level of control groups. Testosterone had not any significant effect on memory impairments of non-castrated rats. According to the obtained results it can be concluded that testosterone improves cognitive and memory impairment of AD.
