Haploinsufficiency in trkB and/or trkC neurotrophin receptors causes structural alterations in the aged hippocampus and amygdala.
Neurotrophins and their cognate trk receptors regulate key events, most notably survival and differentiation of specific neuron populations, during the development of the nervous system. Their functions in the adult and aged CNS are far less well understood. We have analysed mice aged 21-23 months with haploinsufficiencies of the trkB and/or trkC genes with regard to morphological alterations in the hippocampus and amygdala. Neuronal densities and total numbers of neurons in the dentate gyrus were significantly decreased in trkB+/-, trkC+/-, and trkB+/-/C+/- mutants. In the hippocampal area CA2/3, neuronal density and the total number of neurons were only reduced in double-heterozygous mice. Within the amygdala, neuronal densities were not altered. The lateral, basolateral and basomedial nuclei of the amygdala, as well as the dentate gyrus and area CA3, revealed significant increases in the densities of degenerated axonal fragments; the most pronounced changes were found in the double-heterozygous mice. Thus, partial impairment in trkB and/or trkC receptor expression caused region-specific neuron losses in the hippocampus and increased axonal fragmentation in both hippocampus and amygdala, which may result from degeneration of both intrinsic and extrinsic fibre systems. Together, these data indicate that endogenous ligands to the trkB and trkC receptors are essential to maintain neuronal integrity in the aged hippocampus and amygdala.
von Bohlen und Halbach
Oliver
O
Interdisciplinary Center for Neurosciences (IZN), Department of Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany. O.von_Bohlen@web.de
Minichiello
Liliana
L
Unsicker
Klaus
K
D000375:Aging / Q000502:physiology*; D000679:Amygdala / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D002452:Cell Count; D006579:Heterozygote; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology*; D020813:Receptor, trkB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020812:Receptor, trkC / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling
D020813:Receptor, trkB; D020812:Receptor, trkC