| First Author | Kim TA | Year | 2024 |
| Journal | Mol Psychiatry | PubMed ID | 39043843 |
| Mgi Jnum | J:354793 | Mgi Id | MGI:7736439 |
| Doi | 10.1038/s41380-024-02680-9 | Citation | Kim TA, et al. (2024) Neural circuit mechanisms underlying aberrantly prolonged functional hyperemia in young Alzheimer's disease mice. Mol Psychiatry |
| abstractText | Neurovascular defects are one of the most common alterations in Alzheimer's disease (AD) pathogenesis, but whether these deficits develop before the onset of amyloid beta (Abeta) accumulation remains to be determined. Using in vivo optical imaging in freely moving mice, we explored activity-induced hippocampal microvascular blood flow dynamics in App(SAA) knock-in and J20 mouse models of AD at early stages of disease progression. We found that prior to the onset of Abeta accumulation, there was a pathologically elevated blood flow response to context exploration, termed functional hyperemia. After the onset of Abeta accumulation, this context exploration-induced hyperemia declined rapidly relative to that in control mice. Using in vivo electrophysiology recordings to explore the neural circuit mechanism underlying this blood flow alteration, we found that hippocampal interneurons before the onset of Abeta accumulation were hyperactive during context exploration. Chemogenetic tests suggest that hyperactive activation of inhibitory neurons accounted for the elevated functional hyperemia. The suppression of nitric oxide (NO) produced from hippocampal interneurons in young AD mice decreased the accumulation of Abeta. Together, these findings reveal that neurovascular coupling is aberrantly elevated before Abeta deposition, and this hyperactive functional hyperemia declines rapidly upon Abeta accumulation. |
