Galanin hyperinnervates surviving neurons of the human basal nucleus of meynert in dementias of alzheimer's and parkinson's disease: A hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia

Abstract

This study summarizes the findings from postmortem examination of the brains of 22 control cases without neurological deficit, 12 cases of senile dementia of the Alzheimer type (SDAT), and nine cases of Parkinson's disease (three without signs of intellectual deterioration, four with dementia, and two atypical with dementia nonresponsive to L-dopa treatment). The aim of this study was to find the similarities and differences in galanin innervation of the cholinergic basal nucleus neurons in these dementing disorders as compared with controls. Immunocytochemistry with antibodies against galanin peptide and against choline acetyltransferase was applied on perfused brain preparations. Galanin peptide is present in the basal nucleus of Meynert neuron networks in the normal human brain: in local circuit neurons, in a number of galanin/cholinergic neurons, and in a feedback circuit via collaterals) that terminate upon the cholinergic neuronal somata and dendrites. Thus, peptide galanin circuits could function as powerful modulators of the activities of basal nucleus cholinergic neurons, both within the basal forebrain and in their wider projections to the neocortex and amygdala. As galanin has been shown to inhibit cholinergic activity, this galanin network could suppress the activity of cholinergic neurons. In SDAT, there is a primary loss of cholinergic neurons compounded by a secondary reaction of the remaining cholinergic neurons to the terminal degeneration in the cortex. Galanin networks demonstrate an inverse relationship to the cholinergic cell loss. Galanin axons hypertrophy and hyperinnervate the remaining cholinergic neurons. In Parkinson's disease the loss of cholinergic neurons is accentuated by the presence of dementia: the hypertrophy of the galanin axonal networks on cholinergic neurons is dramatic in Parkinson's disease with dementia. These observations throw new light on the neurotransmitter bases for these dementias. Galanin controls cholinergic mechanisms in the basal nucleus of Meynert, and dementia is accompanied by augmentation of galanin innervation onto an already depressed population of cholinergic neurons, thus demonstrating an appreciable amount of plasticity even in aged brain. These findings suggest that the present therapy of cholinergic enhancement as a means to retard intellectual deterioration can by itself have little effect at best, in these dementias. The suppressive effect of galanin peptide has to be reduced or curtailed, perhaps concurrently with the treatment of the cholinergic deficit.(ABSTRACT TRUNCATED AT 400 WORDS)

A role for galanin in human and experimental inflammatory demyelination

“…T he neuropeptide galanin (1) is widely, but by no means ubiquitously, expressed in the adult brain (2)(3)(4)(5), and following injury there is a dramatic increase in the levels of the peptide in many neuronal subpopulations (6)(7)(8) and in the basal forebrain of patients with Alzheimer's disease (9,10). In addition to the neuronal expression of galanin, a small number of reports have shown that the neuropeptide is also expressed by oligodendrocyte or microglial cells following cortical spreading depression (11), transient forebrain ischaemia (12) or colchicine treatment (13,14).…”

Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice

“…One striking aspect of galanin physiology is its robust regulation in the nervous system, particularly in response to insult and injury, after which galanin is dramatically up-regulated in both central and peripheral neurons (Cortes et al, 1990;Zigmond and Sun, 1997). Galanin has also been implicated in the cognitive decline experienced by Alzheimer's disease patients, where it is thought to inhibit the actions of acetylcholine in degenerating memory circuits of the basal forebrain and hippocampus (Chan-Palay, 1988;Steiner et al, 2001).…”

Morphometric study on the CH4 of the nucleus basalis of meynert in Alzheimer’s disease

“…The nbM is usually affected in Alzheimer's disease (AD) resulting in a hypocholinergic condition in the central nervous system, which is associated with mnemonic dysfunction and dementia (Whitehouse et al, 1982). The vulnerability of this nucleus in AD has been ascertained by immunocytochemical procedures, and various studies using morphometric analysis have reported loss and atrophy of the neurons in this nucleus (Allen et al, 1988;Chan-Palay, 1988;Kobayashi et al, 1990;Nakano and Hirano, 1985;Whitehouse et al, 1982). Recent studies have reported that nbM degeneration in AD is associated with hyperinnervation of the galanin-positive nerve cell process or a decrease in the number of neurons with galanin-like immunoreactivity (Chan-Palay, 1988;Vogels et al, 1989).…”

“…The vulnerability of this nucleus in AD has been ascertained by immunocytochemical procedures, and various studies using morphometric analysis have reported loss and atrophy of the neurons in this nucleus (Allen et al, 1988;Chan-Palay, 1988;Kobayashi et al, 1990;Nakano and Hirano, 1985;Whitehouse et al, 1982). Recent studies have reported that nbM degeneration in AD is associated with hyperinnervation of the galanin-positive nerve cell process or a decrease in the number of neurons with galanin-like immunoreactivity (Chan-Palay, 1988;Vogels et al, 1989). The immunohistopathological observation by Chan-Palay (1988) raised the possibility that the cholinergic neurons in the Ch4 may be enlarged in AD and in Parkinson-dementia complex.…”

“…Recent studies have reported that nbM degeneration in AD is associated with hyperinnervation of the galanin-positive nerve cell process or a decrease in the number of neurons with galanin-like immunoreactivity (Chan-Palay, 1988;Vogels et al, 1989). The immunohistopathological observation by Chan-Palay (1988) raised the possibility that the cholinergic neurons in the Ch4 may be enlarged in AD and in Parkinson-dementia complex. Experimental neuropathological studies have demonstrated the unilateral lesions in the neocortex and nucleus basalis lead to contralateral neuronal cell hypertrophy in the nbM (Pearson et al, 1987).…”