Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation

J Comp Neurol. 2001 Apr 2;432(2):197-216. doi: 10.1002/cne.1097.

Abstract

The toxin-antibody complex anti-d(beta)h-saporin (DSAP) selectively destroys d(beta)h-containing catecholamine neurons. To test the role of specific catecholamine neurons in glucoregulatory feeding and adrenal medullary secretion, we injected DSAP, unconjugated saporin (SAP), or saline bilaterally into the paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2-T4) and subsequently tested rats for 2-deoxy-D-glucose (2DG)-induced feeding and blood glucose responses. Injections of DSAP into the PVH abolished 2DG-induced feeding, but not hyperglycemia. 2DG-induced Fos expression was profoundly reduced or abolished in the PVH, but not in the adrenal medulla. The PVH DSAP injections caused a nearly complete loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the area of A1/C1 overlap and severe reduction of A2, C2, C3 (primarily the periventricular portion), and A6 cell groups. Spinal cord DSAP blocked 2DG-induced hyperglycemia but not feeding. 2DG-induced Fos-ir was abolished in the adrenal medulla but not in the PVH. Spinal cord DSAP caused a nearly complete loss of TH-ir in cell groups A5, A7, subcoeruleus, and retrofacial C1 and a partial destruction of C3 (primarily the ventral portion) and A6. Saline and SAP control injections did not cause deficits in 2DG-induced feeding, hyperglycemia, or Fos expression and did not damage catecholamine neurons. DSAP eliminated d(beta)h immunoreactivity but did not cause significant nonspecific damage at injection sites. The results demonstrate that hindbrain catecholamine neurons are essential components of the circuitry for glucoprivic control of feeding and adrenal medullary secretion and indicate that these responses are mediated by different subpopulations of catecholamine neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Medulla / drug effects*
  • Adrenal Medulla / metabolism
  • Animals
  • Antibodies, Monoclonal
  • Antimetabolites / pharmacology
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Deoxyglucose / pharmacology
  • Eating / drug effects*
  • Eating / physiology
  • Epinephrine / metabolism
  • Immunotoxins / pharmacology*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / metabolism
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / injuries
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Proto-Oncogene Proteins c-fos / drug effects*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Antibodies, Monoclonal
  • Antimetabolites
  • Blood Glucose
  • Immunotoxins
  • Proto-Oncogene Proteins c-fos
  • Ribosome Inactivating Proteins, Type 1
  • anti-dopamine beta-hydroxylase immunotoxin
  • Deoxyglucose
  • Saporins
  • Norepinephrine
  • Epinephrine