The length of hippocampal cholinergic fibers is reduced in the aging brain.
Cholinergic deficits occur in the aged hippocampus and they are significant in Alzheimer's disease. Using stereological and biochemical approaches, we characterized the cholinergic septohippocampal pathway in old (24 months) and young adult (3 months) rats. The total length of choline acetyltransferase (ChAT)-positive fibers in the dorsal hippocampus was significantly decreased by 32% with aging (F((1,9))=20.94, p=0.0014), along with the levels of synaptophysin, a presynaptic marker. No significant changes were detected in ChAT activity or in the amounts of ChAT protein, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin related kinase receptor (Trk) A, TrkB, or p75 neurotrophin receptor (p75(NTR)) in the aged dorsal hippocampus. The number and size of ChAT-positive neurons and the levels of ChAT activity, NGF and BDNF were not statistically different in the septum of aged and young adult rats. This study suggests that substantial synaptic loss and cholinergic axonal degeneration occurs during aging and reinforces the importance of therapies that can protect axons and promote their growth in order to restore cholinergic neurotransmission.
Ypsilanti
Athéna Rebecca
AR
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Girão da Cruz
M Teresa
MT
Burgess
Alison
A
Aubert
Isabelle
I
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D048429:Cell Size; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism* / Q000648:ultrastructure*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D018377:Neurotransmitter Agents; D000109:Acetylcholine