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Publication : A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease.

First Author  Chen Y Year  2024
Journal  iScience Volume  27
Issue  5 Pages  109778
PubMed ID  38746665 Mgi Jnum  J:349434
Mgi Id  MGI:7641010 Doi  10.1016/j.isci.2024.109778
Citation  Chen Y, et al. (2024) A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease. iScience 27(5):109778
abstractText  Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5xFAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5xFAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.
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