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Chronic Salt‐Loading Alters Pre‐Autonomic Neuropeptide Expression in the Paraventricular Nucleus
Author(s) -
Smith Justin,
Pati Dipanwita,
Hiller Helmut,
Wang Lei,
Frazier Jason,
Kloet Annette,
Krause Eric
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.652.22
Subject(s) - endocrinology , medicine , vasopressin , hypothalamus , chemistry , in situ hybridization , oxytocin , neuron , excitatory postsynaptic potential , patch clamp , glutamatergic , postsynaptic potential , biology , neuroscience , gene expression , electrophysiology , glutamate receptor , receptor , inhibitory postsynaptic potential , biochemistry , gene
A high‐salt diet and disregulated stress‐responsiveness are known risk‐factors for the development of hypertension and heart disease. Corticotrophin‐releasing factor (CRF) initiates the neuroendocrine response to stressful stimuli and is situated in close proximity to osmosensitive arginine‐vasopressin (AVP) and oxytocin producing neurons in the paraventricular nucleus of the hypothalamus (PVN). To investigate the effect salt‐loading has on CRF neurons, we utilized the Cre‐lox system to generate mice that express red fluorescent protein driven by CRF transcription. These CRF‐reporter mice had water replaced with 2% NaCl for 5 days ending in a 30 min restraint challenge. Compared with mice maintained on water, salt‐loaded mice drank up to 150% more fluid and had significantly higher plasma sodium, but food intakes and body weights were similar. In situ hybridization for CRF mRNA resulted in salt‐loaded mice exhibiting a decreased restraint‐induced CRF expression in the PVN specifically in neurosecretory regions, but an increase in pre‐autonomic areas. Analysis of cells labeled with retrograde tract tracer injected into the ventral‐lateral medulla confirmed an increase in the frequency of pre‐autonomic neurons expressing AVP and CRF in the PVN with salt‐loading. Whole‐cell patch clamp recording of CRF positive PVN cells found significantly fewer spontaneous excitatory postsynaptic currents; however, glutamatergic synapses onto these cells were upregulated. Collectively, these results show the plasticity of stress‐responsive neurons which may contribute to the anxiolytic and cardiovascular effects of high‐salt diets. Support: HL‐096830 (EGK), HL116074 (ADK)