神経科学研究部 大学院1年の成田です。
下記の論文を紹介致します。
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Abstract
Heart failure (HF) patients suffer from cognitive decline and mood
impairments, but the molecular signals and brain circuits underlying
these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT)
is critically involved in regulating mood, and OTergic signalling in
the central amygdala (CeA) is a key mechanism that controls emotional
responses including anxiety-like behaviours. Still, whether an altered
OTergic signalling contributes to mood disorders in HF remains unknown.
To address this, we used an ischaemic rat HF model, along with a highly
multidisciplinary approach, to mechanistically study multiple levels of
the hypothalamus-to-CeA OTergic circuit in male rats with HF. We aimed
to test the hypothesis that sustained activation of the OT system
following an infarct leads to depletion of OT content in this pathway,
with subsequent changes in OT receptor expression and blunted modulation
of local GABAergic circuits. We found that most of OTergic innervation
of the CeA originated from the supraoptic nucleus (SON). While no
differences in the numbers of SON→CeA OTergic neurons was observed
between sham and HF rats, we observed a blunted content and release of
OT from axonal terminals within the CeA. Moreover, we report
downregulation of neuronal and astrocytic OT receptors, and impaired OTR
-driven GABAergic synaptic activity within the CeA microcircuit of HF
rats. We provide the first evidence that male HF rats display
perturbations in the hypothalamus-to-amygdala OTergic circuit, laying
the foundation for future translational studies targeting either the OT
system or GABAergic amygdalar microcircuit to ameliorate mood
impairments in rats or patients with chronic HF.