Synaptic Plasticity in the Dorsal Vagal Complex: Role in Salt Intake and Alteration by Estrogen

다국어 초록 (Multilingual Abstract)

Sodium depletion produced by the natriuretic‐diuretic, furosemide (Furo) stimulates salt intake that increases progressively with repeated Furo treatments. Hormonal, osmotic, and neural signals regarding perturbations in sodium balance are initially processed within neurons and glia of the hindbrain dorsal vagal complex (DVC). Thus, plastic changes to glia and synaptic proteins can alter the effectiveness of synapses in the dorsal vagal complex to propagate signals to forebrain areas involved in body fluid regulation and thereby produce progressive increases in salt intake. Central actions of estrogen contribute to sex differences in a variety of adaptive behaviors, including salt intake in response to Furo treatment. Therefore, our objective was to assess the effect of estrogen on the expression of glial fibrillary acidic protein (GFAP; a marker for glia) and synaptotagmin 4 and calcium calmodulin kinase II (SYT4 CaMKII; synaptic proteins) in the DVC in response to repeated treatments with Furo. Adult female rats were ovariectomized, allowed to recover for 7 days, and then given estradiol benzoate (EB; 10 μg/0.1 ml oil, sc) or oil vehicle (OIL; 0.1 ml, sc) each week for 3 weeks. Rats were injected weekly with Furosemide (5 mg/kg, sc) or 0.15 M NaCl 18–24 hours after injection on week 1 and 2; and rats were also given 3‐hr access to one bottle of deionized water and one bottle of 0.5 M NaCl (salt) without food. On week 3, rats were terminated via decapitation 18–24 hours after the second injection, and the brains were flash frozen in liquid nitrogen, homogenized, and stored at −80°C. Frozen tissue punches from DVC were immunoblotted for GFAP (Millipore MAB360 mouse anti‐GFAP; 1:6000), CaMKII (Thermo Fisher MA1‐048 mouse anti‐CaMKII; 1:2000), synaptotagmin 4 (Thermo Fisher PA5‐52709 rabbit anti‐SYT4; 1:250), and β‐actin (#4970; Cell Signaling rabbit anti‐ β‐actin; 1:1000). Salt intake was increased in furosemide treated rats compared to isosaline treated rats independent of number of depletions. Estradiol produced a greater increase in salt intake compared to oil‐treated rats after first furosemide‐induced sodium depletion. Water intake was increased in furosemide treated rats compared to isosaline treated rats. Repeated furosemide treatment altered the expression of GFAP, SYT4, and CaMKII in the DVC. Preliminary analysis suggests estradiol may alter expression of GFAP, SYT4, and CaMKII in the DVC.
Support or Funding Information
Supported by OCAST HR12‐196
This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.