Spatial memory impairment by TRPC1 depletion is ameliorated by environmental enrichment

Abstract

Canonical transient receptor potential (TRPC) channels are widely expressed throughout the nervous system whereas their functions remain largely unclear. Here we investigated the effects of TRPC1 deletion on spatial memory ability of mice and the potential intervention by environmental enrichment (EE). Significant spatial memory impairment assessed by conditional fearing test, Y maze test and step-down test in TRPC1 knockout mice was revealed. The behavioral abnormality were attenuated by the treatment of EE. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with a matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) and tandem mass spectrometry (MS) revealed that TRPC1 deletion caused differential expression of a total of 10 proteins (8 up-regulated and 2 down-regulated) in hippocampus. EE treatment resulted in differential expression of a total of 22 proteins (2 up-regulated and 20 down-regulated) in hippocampus of TRPC1 knockout mice. Among these differentially expressed proteins, the expression of α-internexin and glia maturation factor β (GMF-β), two proteins shown to impair memory, were significantly down-regulated in hippocampus of TRPC1 knockout mice by EE treatment. Taken together, these data suggested that TRPC1 regulated directly or indirectly the expression of multiple proteins, which may be crucial for the maintenance of memory ability, and that EE treatment modulated spatial memory impairment caused by TRPC1 depletion and the mechanisms may involve the modulation of EE on the expression of those dys-regulated proteins such as α-internexin and GMF-β in hippocampus.

Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory

“…In contrast to our results, Xing et al have suggested impairments in spatial memory, due to the genetic ablation of Trpc1 (Xing et al, 2016). However, the unconventional Y-maze protocol applied in the study of Xing et al does neither specifically assess spontaneous alternation, spatial working, nor reference memory, as it has been reliably shown by other groups (Hughes, 2004;Fuchs et al, 2007).…”

Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory

“…Histologic examination of brain slices did not reveal any major difference between WT and Trpc1 -/- mice. However, TRPC1 has been shown to modulate the expression of several proteins that could play a role in memory, such as α-internexin and glia maturation factor β ( Xing et al, 2016 ). Moreover, as TRPC1 is known to heteromultimerize with TRPC4 and/or TRPC5, we cannot exclude that, in the absence of TRPC1, these complexes might be differently localized in the cell, even if there expression is unchanged ( Figure 1E ).…”

Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone

“…Genetic deletion of Orai1 or TRPC1 has been related to alterations in the immune system as well as to impairments in skin integrity, muscle function and regeneration or intestinal mucosa restitution after wounding [32,33,36,37]. In the brain, ablation of TRPC1 or STIM1 in knockout mice results in memory deficiencies [54,55]. Interestingly, adult neurogenesis has been implicated in learning and memory in both rodents and humans [56,57] and learning defects induced by impairment of neurogenesis could be reversed by restoring neurogenesis [58][59][60][61].…”