1. Mutation in Sodium-Glucose Cotransporter 2 Results in Down-Regulation of Amyloid Beta (A4) Precursor-Like Protein 1 in Young Age, Which May Lead to Poor Memory Retention in Old Age
- Author
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Yoshiichi Takagi, Mitsuhiro Suzuki, Tadashi Hase, Sanae Hasegawa-Ishii, Tomokazu Konishi, Takumi Kurotaki, Yoriyuki Nakamura, Monira Pervin, Kyoko Taguchi, Akiyuki Miyake, Keiko Unno, Shinichi Meguro, and Atsuyoshi Shimada
- Subjects
0301 basic medicine ,Aging ,medicine.medical_treatment ,lcsh:Chemistry ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,glucosuria ,lcsh:QH301-705.5 ,Spectroscopy ,Cellular Senescence ,Age Factors ,Brain ,Neurodegenerative Diseases ,General Medicine ,amyloid beta (A4) precursor-like protein 1 ,Computer Science Applications ,Sodium/Glucose Cotransporter 2 ,medicine.medical_specialty ,Amyloid ,Amyloid beta ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Atrophy ,Sodium-Glucose Transporter 2 ,Memory ,Internal medicine ,medicine ,Animals ,Humans ,APLP1 ,Physical and Theoretical Chemistry ,Molecular Biology ,senescence-accelerated mouse prone 10 ,Cerebral atrophy ,Memory Disorders ,Insulin ,Organic Chemistry ,sodium-glucose cotransporter 2 ,medicine.disease ,Synapsins ,memory retention ,030104 developmental biology ,Endocrinology ,Glucose ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene Expression Regulation ,Mutation ,biology.protein ,030217 neurology & neurosurgery ,Homeostasis - Abstract
Senescence-accelerated mouse prone 10 (SAMP10) exhibits cerebral atrophy and depression-like behavior. A line of SAMP10 with spontaneous mutation in the Slc5a2 gene encoding the sodium-glucose cotransporter (SGLT) 2 was named SAMP10/TaSlc-Slc5a2slc (SAMP10-&Delta, Sglt2) and was identified as a renal diabetes model. In contrast, a line of SAMP10 with no mutation in SGLT2 (SAMP10/TaIdrSlc, SAMP10(+)) was recently established under a specific pathogen-free condition. Here, we examined the mutation effect in SGLT2 on brain function and longevity. No differences were found in the survival curve, depression-like behavior, and age-related brain atrophy between SAMP10-&Delta, Sglt2 and SAMP10(+). However, memory retention was lower in SAMP10-&Delta, Sglt2 mice than SAMP10(+). Amyloid beta (A4) precursor-like protein 1 (Aplp1) expression was significantly lower in the hippocampus of SAMP10-&Delta, SGLT2 than in SAMP10(+) at 2 months of age, but was similar at 12 months of age. CaM kinase-like vesicle association (Camkv) expression was remarkably lower in SAMP10(+). These genes have been reported to be involved in dendrite function. Amyloid precursor proteins have been reported to involve in maintaining homeostasis of glucose and insulin. These results suggest that mutation in SGLT2 results in down-regulation of Aplp1 in young age, which can lead to poor memory retention in old age.
- Published
- 2020