A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease
A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzhe...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2016-10-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/2565.pdf |
| _version_ | 1827607715407462400 |
|---|---|
| author | Erik C.B. Johnson Jing Kang |
| author_facet | Erik C.B. Johnson Jing Kang |
| author_sort | Erik C.B. Johnson |
| collection | DOAJ |
| description | A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer’s disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice. We also did not observe a significant enhancement of spatial learning or memory in nontransgenic mice with ISRIB treatment, although a trend emerged for memory enhancement in one cohort of mice. Future preclinical studies with ISRIB would benefit from additional robust markers of target engagement in the brain. |
| first_indexed | 2024-03-09T07:00:09Z |
| format | Article |
| id | doaj.art-7c52e330cb8644c18a00cef0991af5d1 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:00:09Z |
| publishDate | 2016-10-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-7c52e330cb8644c18a00cef0991af5d12023-12-03T09:55:49ZengPeerJ Inc.PeerJ2167-83592016-10-014e256510.7717/peerj.2565A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s diseaseErik C.B. Johnson0Jing Kang1Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, United StatesGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, United StatesA small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer’s disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice. We also did not observe a significant enhancement of spatial learning or memory in nontransgenic mice with ISRIB treatment, although a trend emerged for memory enhancement in one cohort of mice. Future preclinical studies with ISRIB would benefit from additional robust markers of target engagement in the brain.https://peerj.com/articles/2565.pdfISRIBAlzheimer’s diseaseJ20 mouse modelLearning and memory |
| spellingShingle | Erik C.B. Johnson Jing Kang A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease PeerJ ISRIB Alzheimer’s disease J20 mouse model Learning and memory |
| title | A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease |
| title_full | A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease |
| title_fullStr | A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease |
| title_full_unstemmed | A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease |
| title_short | A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease |
| title_sort | small molecule targeting protein translation does not rescue spatial learning and memory deficits in the happ j20 mouse model of alzheimer s disease |
| topic | ISRIB Alzheimer’s disease J20 mouse model Learning and memory |
| url | https://peerj.com/articles/2565.pdf |
| work_keys_str_mv | AT erikcbjohnson asmallmoleculetargetingproteintranslationdoesnotrescuespatiallearningandmemorydeficitsinthehappj20mousemodelofalzheimersdisease AT jingkang asmallmoleculetargetingproteintranslationdoesnotrescuespatiallearningandmemorydeficitsinthehappj20mousemodelofalzheimersdisease AT erikcbjohnson smallmoleculetargetingproteintranslationdoesnotrescuespatiallearningandmemorydeficitsinthehappj20mousemodelofalzheimersdisease AT jingkang smallmoleculetargetingproteintranslationdoesnotrescuespatiallearningandmemorydeficitsinthehappj20mousemodelofalzheimersdisease |