Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice.
TrkA high-affinity receptors are essential for the normal development of sympathetic paravertebral neurons and subpopulations of sensory neurons. Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which aspects of development of the adrenal medulla might be regulated via TrkA are unknown. In the present study we demonstrate that mice deficient for TrkA, but not the neurotrophin receptor TrkB, show an early postnatal progressive reduction of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in preganglionic sympathetic neurons within the thoracic spinal cord, which are also significantly reduced in number. Quantitative determinations of specific AChE activity revealed a massive decrease (-62%) in the adrenal gland and a lesser, but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers of the adrenal medulla and its innervation, including various neuropeptides, chromogranin B, secretogranin II, amine transporters, the catecholamine-synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1, essentially were unchanged. Interestingly, AChE immunoreactivity appeared unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal medullary cells, do not express TrkA. They must, therefore, be affected indirectly by the TrkA knock-out, possibly via a retrograde signal from chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves.
Schober
A
A
Department of Anatomy and Cell Biology III, University of Heidelberg, Germany.
Minichiello
L
L
Keller
M
M
Huber
K
K
Layer
P G
PG
Roig-López
J L
JL
García-Arrarás
J E
JE
Klein
R
R
Unsicker
K
K
D000110:Acetylcholinesterase / Q000378:metabolism*; D000313:Adrenal Medulla / Q000737:chemistry / Q000201:enzymology*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000201:enzymology* / Q000503:physiopathology; D002395:Catecholamines / Q000032:analysis; D019439:Chromaffin Cells; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency*
D002395:Catecholamines; D020794:Receptor Protein-Tyrosine Kinases; D000110:Acetylcholinesterase