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Neuronal Nitric Oxide Inhibitor 7-Nitroindazole Improved Brain-Derived Neurotrophic Factor and Attenuated Brain Tissues Oxidative Damage and Learning and Memory Impairments of Hypothyroid Juvenile Rats

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Abstract

Hypothyroidism-associated learning and memory impairment is reported to be connected to oxidative stress and reduced levels of brain-derived neurotrophic factor (BDNF). The effects of neuronal nitric oxide inhibitor 7-nitroindazole (7NI) on brain tissues oxidative damage, nitric oxide (NO), BDNF and memory impairments in hypothyroid juvenile rats were investigated. Male Wistar juvenile rats (20 days old) were divided into five groups, including Martinez et al. (J Neurochem 78 (5):1054–1063, 2001). Control in which vehicle was injected instead of 7NI, (Jackson in Thyroid 8 (10):951–956, 1998) Propylthiouracil (PTU) where 0.05% PTU was added in drinking water and vehicle was injected instead of 7NI, (Gong et al. in BMC Neurosci 11 (1):50, 2010; Alva-Sánchez et al. in Brain Res 1271:27–35, 2009; Anaeigoudari et al. in Pharmacol Rep 68 (2): 243–249, 2016) PTU-7NI 5, PTU-7NI 10 and PTU-7NI 20 in which 5, 10, or 20 mg/kg7NI was injected intraperitoneally (i.p.). Following 6 weeks, Morris water maze (MMW) and passive avoidance learning (PAL) tests were used to evaluate the memory. Finally, the hippocampus and the cortex of the rats were removed after anesthesia by urethane to be used for future analysis. The escape latency and traveled path in MWM test was increased in PTU group (P < 0.001). PTU also reduced the latency to enter the dark box of PAL and the time spent and the distance in the target quadrant in MWM test (P < 0.001 and P < 0.01). Treatment with 7NI attenuated all adverse effects of PTU (P < 0.05 to P < 0.001). PTU lowered BDNF and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain but increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. In addition, 7NI improved thiol, SOD, CAT, thiol, and BDNF but attenuated MDA and NO metabolites. The results of the current study showed that 7NI improvement in the learning and memory of the hypothyroid juvenile rats, which was accompanied with improving of BDNF and attenuation of NO and brain tissues oxidative damage.

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Acknowledgements

The authors are grateful to the Vice President of Research in Semnan (Grant number: 1492) and Mashhad University of Medical Sciences (Grant number: 960265) for the financial support.

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Authors and Affiliations

  1. Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Sara Memarpour, Abbas Ali Vafaei & Ali Rashidy-Pour

  2. Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Farimah Beheshti

  3. Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Farimah Beheshti

  4. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Yousef Baghcheghi

  5. Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Hosseini

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  1. Sara Memarpour
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Memarpour, S., Beheshti, F., Baghcheghi, Y. et al. Neuronal Nitric Oxide Inhibitor 7-Nitroindazole Improved Brain-Derived Neurotrophic Factor and Attenuated Brain Tissues Oxidative Damage and Learning and Memory Impairments of Hypothyroid Juvenile Rats. Neurochem Res 45, 2775–2785 (2020). https://doi.org/10.1007/s11064-020-03128-6

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