Cholinergic activity and amyloid precursor protein metabolism.

With more than 4 million Alzheimer's victims nationwide, there is intense research to elucidate the relationship among the hallmarks of the disease, amyloid plaques, neurofibrillary tangles, and degeneration of the basal forebrain cholinergic neurons. There has been much debate about which of these is the primary lesion, and which develops secondarily. The correlation between plaques and tangles and dementia is not absolute, but a consistent feature of Alzheimer's disease is loss of cortical and hippocampal cholinergic function as a result of basal forebrain compromise. Additionally, factors associated with the cholinergic system have been shown to influence the processing and metabolism of the amyloid precursor, a protein that contains the amyloidogenic sequence found in plaques. In this paper, the relationship between cholinergic compromise and amyloid deposition, as well as the cholinergic system-associated factors which appear to participate in amyloid precursor protein processing, are discussed.

Cholinergic denervation and sympathetic ingrowth result in persistent changes in hippocampal muscarinic receptors.

Our laboratory has been utilizing the model of hippocampal sympathetic ingrowth, which has been suggested to occur in Alzheimer's disease, to investigate the effects of cholinergic denervation and hippocampal rearrangements. After cholinergic denervation by medial septal lesions, peripheral sympathetic fibres originating from the superior cervical ganglia grow into the rat hippocampus. This hippocampal sympathetic ingrowth can be prevented by superior cervical ganglionectomy. We examined the long-term effects of these treatments on muscarinic receptors by comparing [3H]quinuclidinyl benzilate binding in rat dorsal hippocampus four and 12 weeks post lesion. Four groups of animals were employed, including controls (sham lesion+sham ganglionectomy), animals with ingrowth (medial septal lesion+ sham ganglionectomy), animals with cholinergic denervation alone (medial septal lesion+ ganglionectomy), and ganglionectomy alone (sham lesion+ganglionectomy) animals. In dorsal hippocampus four weeks post lesion, binding affinity was similar among all groups, while muscarinic receptor number was increased in ingrowth animals as compared to both the control (P<0.0002) and ganglionectomy animals (P<0.01). By 12 weeks, receptor affinity was significantly decreased in ingrowth (P<0.0001) and cholinergic denervation (P<0.0003) groups, and receptor number remained significantly elevated in ingrowth animals as compared to control (P<0.01), ganglionectomy (P<0.02) and cholinergic denervation (P<0.01) groups. The decrease in muscarinic receptor affinity may provide some insight into the ineffectiveness of cholinomimetic therapies in Alzheimer's disease, in that agonist efficacy would be reduced at the receptor.

Using Orem's theory in transcultural settings: a critique.

An overview of the theory describes its component parts and concepts as well as the premises and assumptions upon which the theory is based. The authors explore the compatibility and usefulness of Orem's theory with non-Western or minority Western non-Anglo values and belief systems. A literature review of studies and experiences using Orem's theory in a variety of cultures is presented and discussed. The authors conclude that Orem's theory must be supplemented or replaced by one less culturebound for use with cultures differing from the dominant Western culture.