title: Astrocytes in the rat nucleus tractus solitarii are critical for cardiovascular reflex control.
abstract: We have shown that an antibody to dopamine-β-hydroxylase conjugated with saporin (anti-DBH-SAP) damages catecholamine neurons in the nucleus tractus solitarii (NTS) of rat, attenuates arterial baroreflexes, and leads to lability of arterial blood pressure, damage to cardiac myocytes, and, in some animals, sudden death. However, others have shown that injection of 6-hydroxydopamine (6-OHDA), a toxin devoid of saporin, also damaged NTS catecholamine neurons but did not lead to these cardiovascular changes. We found similar cardiovascular changes after injecting a different SAP conjugate to target NTS neurons with neurokinin (NK1) receptors. Because ribosome-inactivating proteins may be toxic to glia, we hypothesized that SAP, a ribosome-inactivating protein, might target glia whose loss could account for physiological changes. We tested this hypothesis by assessing effects on select neurons and on glia in the NTS after exposure to SAP, targeted SAP conjugates, or 6-OHDA. SAP and all SAP conjugates led to loss of immunoreactivity for glial fibrillary acidic protein, a marker for astrocytes, in the NTS while 6-OHDA did not. As reported previously, anti-DBH-SAP selectively killed noradrenergic neurons in the NTS while SAP conjugated to stabilized substance P (SSP-SAP) selectively killed neurons with NK1 receptors. In contrast, SAP produced no demonstrable neuronal damage. All injections led to activation of microglia in the NTS; however, only SAP and its conjugates attenuated cardiovascular reflexes while also producing lability of arterial pressure, damage to cardiac myocytes, and in some animals, sudden death. Thus, NTS astrocytes may play a role in mediating cardiovascular reflex transmission through the NTS.
authors.affiliation: Laboratory of Neurobiology, Department of Neurology, Carver College of Medicine, The University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52242, and Department of Pathology, Caver College of Medicine, The University of Iowa, Iowa City, Iowa 52242.
authors.forename: Li-Hsien
authors.initials: LH
authors.lastname: Lin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Jones
authors.forename: Jacob
authors.initials: J
authors.lastname: McGlashon
authors.forename: William T
authors.initials: WT
authors.lastname: Talman
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009206:Myocardium / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D017552:Solitary Nucleus / Q000166:cytology* / Q000187:drug effects
chemical_list: D018663:Adrenergic Agents; D005904:Glial Fibrillary Acidic Protein; D000922:Immunotoxins; D009419:Nerve Tissue Proteins; D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; D016627:Oxidopamine; D000076985:Saporins