Cholinergic medial septum neurons do not degenerate in aged 129/Sv control or p75(NGFR)-/-mice.
Cholinergic medial septum neurons express TrkA and p75 nerve growth factor receptor (p75(NGFR)) and interactions between TrkA and p75(NGFR) are necessary for high-affinity binding and signaling of nerve growth factor (NGF) through TrkA. In adult p75(NGFR)-deficient (-/-) mice, retrograde transport of NGF and other neurotrophins by these neurons is greatly reduced, however, these neurons maintain their cholinergic phenotype and size. Reduced transport of NGF has been proposed to play a role in Alzheimer's disease. Here, we investigated whether chronic and long-term absence of p75(NGFR) (and possibly reduced NGF transport and TrkA binding) would affect the cholinergic septohippocampal system during aging in mice. In young (6-8 months), middle aged (12-18 months), and aged (19-23 months) 129/Sv control mice the total number of choline acetyltransferase-positive medial septum neurons and the mean diameter and cross sectional area of the cholinergic cell bodies were similar. The cholinergic hippocampal innervation, as measured by the density of acetylcholinesterase-positive fibers in the outer molecular layer of the dentate gyrus was also similar across all ages. These parameters also did not change during aging in p75(NGFR) -/- mice and the number and size of the choline acetyltransferase-positive neurons and the cholinergic innervation density were largely similar as in control mice at all ages. These results suggest that p75(NGFR) does not play a major role in the maintenance of the number or morphology of the cholinergic basal forebrain neurons during aging of these mice. Alternatively, p75(NGFR) -/- mice may have developed compensatory mechanisms in response to the absence of p75(NGFR).
Ward
N L
NL
Department of Anatomy and Neurobiology, Tupper Building, Dalhousie University, Halifax, N.S, Canada.
Stanford
L E
LE
Brown
R E
RE
Hagg
T
T
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000201:enzymology; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics*; D012686:Septal Nuclei / Q000166:cytology* / Q000201:enzymology*; D012737:Sex Factors
D020800:Receptor, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase