CX۶۹۱ as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer’s disease

Objective(s): Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-۳-hydroxy-۵-methyl-۴-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer’s disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX۶۹۱, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. Materials and Methods: For induction of AD, amyloid-beta ۱-۴۲ (Aβ۱-۴۲) was microinjected into the hippocampus of male Wistar rats (۲۵۰-۳۰۰ g). The Morris water maze (MWM) test was used to evaluate the effect of CX۶۹۱ (۰.۰۳ and ۰.۳ mg/kg, twice a day for ۱۰ days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. Results: The obtained data showed that treatment with CX۶۹۱ (۰.۳ mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX۶۹۱ (۰.۳ mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.Conclusion: The CX۶۹۱ can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Keywords:

Alzheimer’s disease , AMPA receptors , BDNF , CX۶۹۱ , Memory , Rat