title: The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25 and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive impairment.
abstract: Changes of synaptic proteins in highlighted brain regions and decreased serum thyroid hormones (THs) have been implied in age-related learning and memory decline. Previously, we showed significant pairwise correlations among markedly impaired spatial learning and memory ability, decreased serum free triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old Kunming mice. However, whether these changes and the correlations occur in middle-age mice remains unclear. Since this age is one of the best stages to study age-related cognitive decline, we explored the spatial learning and memory ability, serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle-aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19 mice aged 6 months and 16 mice aged 12 months) were measured with a radial six-arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. The results showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both learning and memory phases of the RAWM. The Pearson's correlation test showed that the DH SANP-25 and Munc18-1 levels were positively correlated with the number of errors and latency in learning phases of the RAWM. Meanwhile, the DH SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels might be involved in the spatial learning ability decline in the middle-aged mice.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China; Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Qi-Gang
authors.initials: QG
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Gui-Hai
authors.initials: GH
authors.lastname: Chen
mesh_terms: D000375:Aging; D000818:Animals; D003072:Cognition Disorders / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D051938:Munc18 Proteins / Q000378:metabolism*; D010296:Parietal Lobe / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D051938:Munc18 Proteins; C494209:Snap25 protein, mouse; C497938:Stxbp1 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D014284:Triiodothyronine
keywords: Aging; Brain; Learning and memory; Munc18-1; SNAP-25; Thyroid hormone