Dorsal raphe nucleus-hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice.
Transl Neurodegener
; 13(1): 34, 2024 Jul 24.
Article
in En
| MEDLINE
| ID: mdl-39044270
ABSTRACT
BACKGROUND:
Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression.METHODS:
We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model.RESULTS:
We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity.CONCLUSIONS:
These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mice, Transgenic
/
Depression
/
Disease Models, Animal
/
Serotonergic Neurons
/
Alzheimer Disease
/
Cognitive Dysfunction
/
Dorsal Raphe Nucleus
Limits:
Animals
Language:
En
Journal:
Transl Neurodegener
/
Translational neurodegeneration
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido