Aminoguanidine reverses cognitive deficits and activation of cAMP/CREB/BDNF pathway in mouse hippocampus after traumatic brain injury (TBI)

ABSTRACT

Primary Objective: We aim to study the effects of chronic aminoguanidine (AG) administration on learning and memory impairment after TBI and explore the potential mechanism involved in this process.

Research Design: Male C57BL/6J mice were divided into 6 groups: Control, TBI + Veh, TBI+ AG (50, 100, 200 and 400 mg/kg, i.p.).

Methods and Procedures: Then, we measured cyclicadenosine 3ʹ, 5ʹ-monophosphate (cAMP) content, phosphorylated form of cAMP-response element binding protein (p-CREB) level, iNOS, brain-derived neurotrophic factor (BDNF) and postsynaptic density-93/95 (PSD-93/95) expression in hippocampus. The learning and memory abilities were assessed using Morris water maze and step-down test.

Main Outcomes and Results: The results demonstrate that TBI induced down-regulation of BDNF, loss of PSD-93/95, learning and memory deficits with down-regulation of cAMP content and p-CREB/CREB ratio. Administration of AG (200 and 400 mg/kg) reversed TBI induced down-regulation of BDNF and PSD-93/95, up-regulated the cAMP content and p-CREB/CREB ratio, which resulted in improvement of learning and memory ability.

Conclusions: We suspect that AG (200 and 400 mg/kg) might reverse TBI-induced selective loss of postsynaptic proteins and learning and memory deficits with the activation of cAMP/CREB/BDNF signalling pathway.

KEYWORDS:

• Traumatic brain injury (TBI)
• aminoguanidine
• cAMP/CREB/BDNF pathway
• brain-derived neurotrophic factor (BDNF)
• postsynaptic proteins
• learning and memory

Conflict of interest

All authors have declared no conflict of interest associated with this project.

Additional information

Funding

This project was supported by Key Research and Development Plan Projects (Social Development) in Huai’an city of Jiangsu Province (No. HAS2015018) for Lianshu Ding and the Natural Science Research Program in Huai’an city of Jiangsu Province (HAB201726) for Weijie Wang.