| First Author | Li H | Year | 2022 |
| Journal | Neurobiol Aging | Volume | 117 |
| Pages | 165-178 | PubMed ID | 35764035 |
| Mgi Jnum | J:358955 | Mgi Id | MGI:7316207 |
| Doi | 10.1016/j.neurobiolaging.2022.05.013 | Citation | Li H, et al. (2022) Loss of SST and PV positive interneurons in the ventral hippocampus results in anxiety-like behavior in 5xFAD mice. Neurobiol Aging 117:165-178 |
| abstractText | Neuropsychiatric symptoms, such as anxiety and depression often appear early in patients with Alzheimer's disease (AD), and a comorbid, anxiety-like phenotype is also found in rodents with AD. However, the underlying mechanisms behind these conditions and potential therapeutic targets to treat them remain unclear. In this study, we used 5 familial AD mutations (5xFAD) mice that developed early amyloid beta-amyloid deposition and related synaptic loss and memory deficits to identify a potential mechanism behind abnormally high anxiety levels observed in these subjects. We observed anxiety-like behavior in mice that had an excitatory/inhibitory (E/I) imbalance in the ventral hippocampus (vHPC) of 5xFAD mice. Both the number of parvalbumin-positive (PV+) and somatostatin-positive (SST+) cells decreased in the ventral hippocampus of the subject 5xFAD mice, however, no reductions were observed in calretinin-positive cells. We found that selectively inhibiting vHPC pyramidal cells via hM4Di expression normalized anxiety-like behaviors and E/I balance in 5xFAD mice. Finally, we found that the ventral hippocampus SST+ or PV+ neurons were activated through selectively expressed hM3Dq, which ameliorated anxiety-like behaviors and the synaptic E/I imbalance of vCA1 in 5xFAD mice. These results determined that anxiety-like behaviors accompanied by hippocampal synaptic E/I imbalance in 5xFAD mice are due to the loss of SST+ and PV+ interneurons in the vHPC. This provides a better understanding of high anxiety levels observed in patients with early-stage AD. |
