The change of spatial cognition ability in depression rat model and the possible association with down-regulated protein expression of TRPC6

• Impaired cognitive ability was observed in a chronic unpredictable stress rat model.
• TRPC6 decreased in hippocampus along with impairment of spatial cognitive ability.
• Hyperforin enhanced neurite spine density of hippocampal neurons.
• TRPC6 channels are critical for maintaining spine density and morphology.

An increasing number of researches have focused on the cognitive changes in depression patients. Here, we observed impaired cognitive ability in a rat depression model along with down-regulated expression of canonical transient receptor potential 6 (TRPC6) protein. The cognitive defect could be rescued by treatment with hyperforin, which can invoke TRPC6 activation. This study was designed as following: rats were randomly divided into control, stressed and stressed + hyperforin groups. Chronic unpredictable stress combined with isolation rearing was applied on rats for three weeks, except for control group. Morris water maze was applied to evaluate spatial cognitive ability while long-term potentiation (LTP) was recorded to test the synaptic plasticity. Results showed that both spatial cognition and synaptic plasticity were impaired in stress group while improved after hyperforin treatment in stressed + hyperforin group, meanwhile, Western blot assay showed that TRPC6 expression was decreased in stressed group. The histological data also presented the decline of dendritic length, dendritic spine density and the number of excitatory synapses in stress group while they were increased in stressed + hyperforin group. These results suggest that there is a well potential of TRPC6 to become a new target for selecting promising new candidates as antidepressants with therapeutically effect on impaired cognition.

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