title: 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)
authors: Neurology Clinic, University Hospital, Zurich, Switzerland.
authors: V
authors: V
authors: Chan-Palay
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D001479:Basal Ganglia / Q000503:physiopathology*; D001921:Brain / Q000033:anatomy & histology; D005260:Female; D019004:Galanin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D010455:Peptides / Q000502:physiology*; D013377:Substantia Innominata / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009479:Neuropeptides; D010455:Peptides; D019004:Galanin; D000109:Acetylcholine