The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice
Insulin is known to act in the central nervous system to regulate several physiological and behavioural outcomes, including energy balance, glucose homeostasis and cognitive functioning. However, the neuronal populations through which insulin enhances cognitive performance remain unidentified. In...
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| Format: | Article |
| Language: | English |
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IMR Press
2022-01-01
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| Series: | Journal of Integrative Neuroscience |
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| Online Access: | https://article.imrpress.com/journal/JIN/21/1/10.31083/j.jin2101006/1757-448X-21-1-006.pdf |
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| author | Elisabeth K. Goodman Caitlin S. Mitchell Jonathan D. Teo Joanne M. Gladding Kirsten N. Abbott Neda Rafiei Lei Zhang Herbert Herzog Denovan P. Begg |
| author_facet | Elisabeth K. Goodman Caitlin S. Mitchell Jonathan D. Teo Joanne M. Gladding Kirsten N. Abbott Neda Rafiei Lei Zhang Herbert Herzog Denovan P. Begg |
| author_sort | Elisabeth K. Goodman |
| collection | DOAJ |
| description | Insulin is known to act in the central nervous system to regulate several
physiological and behavioural outcomes, including energy balance, glucose
homeostasis and cognitive functioning. However, the neuronal populations through
which insulin enhances cognitive performance remain unidentified. Insulin
receptors are found in neuropeptide-Y (NPY) expressing neurons, which are
abundant in the hypothalamus and hippocampus; regions involved in feeding
behaviour and spatial memory, respectively. Here we show that mice with a tissue
specific knockout of insulin receptors in NPY expressing neurons
(IRlox/lox; NPYCre/+) display an impaired performance in the probe trial
of the Morris Water Maze compared with control mice at both the 6 and the 12, but
not at the 24 months time point, consistent with a crucial role of insulin and
NPY in cognitive functioning. By 24 months of age all groups demonstrated similar
reductions in spatial memory performance. Together, these data suggest that the
mechanisms through which insulin influences cognitive functioning are, at least
in part, via insulin receptor signaling in NPY expressing neurons. These results
also highlight that cognitive impairments observed in aging may be due to
impaired insulin signaling. |
| first_indexed | 2024-12-12T17:20:54Z |
| format | Article |
| id | doaj.art-387e1f697f3046f1bfa3e83f54b50132 |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-12-12T17:20:54Z |
| publishDate | 2022-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-387e1f697f3046f1bfa3e83f54b501322022-12-22T00:17:38ZengIMR PressJournal of Integrative Neuroscience0219-63522022-01-0121100610.31083/j.jin2101006S0219-6352(22)00266-2The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging miceElisabeth K. Goodman0Caitlin S. Mitchell1Jonathan D. Teo2Joanne M. Gladding3Kirsten N. Abbott4Neda Rafiei5Lei Zhang6Herbert Herzog7Denovan P. Begg8School of Psychology, UNSW Sydney, 2052 Sydney, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaGarvan Institute of Medical Research, 2010 Darlinghurst, AustraliaGarvan Institute of Medical Research, 2010 Darlinghurst, AustraliaSchool of Psychology, UNSW Sydney, 2052 Sydney, AustraliaInsulin is known to act in the central nervous system to regulate several physiological and behavioural outcomes, including energy balance, glucose homeostasis and cognitive functioning. However, the neuronal populations through which insulin enhances cognitive performance remain unidentified. Insulin receptors are found in neuropeptide-Y (NPY) expressing neurons, which are abundant in the hypothalamus and hippocampus; regions involved in feeding behaviour and spatial memory, respectively. Here we show that mice with a tissue specific knockout of insulin receptors in NPY expressing neurons (IRlox/lox; NPYCre/+) display an impaired performance in the probe trial of the Morris Water Maze compared with control mice at both the 6 and the 12, but not at the 24 months time point, consistent with a crucial role of insulin and NPY in cognitive functioning. By 24 months of age all groups demonstrated similar reductions in spatial memory performance. Together, these data suggest that the mechanisms through which insulin influences cognitive functioning are, at least in part, via insulin receptor signaling in NPY expressing neurons. These results also highlight that cognitive impairments observed in aging may be due to impaired insulin signaling.https://article.imrpress.com/journal/JIN/21/1/10.31083/j.jin2101006/1757-448X-21-1-006.pdfinsulin receptorsnpyspatial memoryhippocampusmorris water maze |
| spellingShingle | Elisabeth K. Goodman Caitlin S. Mitchell Jonathan D. Teo Joanne M. Gladding Kirsten N. Abbott Neda Rafiei Lei Zhang Herbert Herzog Denovan P. Begg The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice Journal of Integrative Neuroscience insulin receptors npy spatial memory hippocampus morris water maze |
| title | The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice |
| title_full | The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice |
| title_fullStr | The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice |
| title_full_unstemmed | The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice |
| title_short | The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice |
| title_sort | effect of insulin receptor deletion in neuropeptide y neurons on hippocampal dependent cognitive function in aging mice |
| topic | insulin receptors npy spatial memory hippocampus morris water maze |
| url | https://article.imrpress.com/journal/JIN/21/1/10.31083/j.jin2101006/1757-448X-21-1-006.pdf |
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