No abstract

The present study provides qualitative and quantitative investigations of the norepinephrine (NE) neurons in the locus coeruleus (LC) in two neurodegenerative disorders, the senile dementia of the Alzheimer type (SDAT) and Parkinson's disease (PD). The group of PD subjects was subdivided into cases without dementia (P - D), cases with dementia, L-dopa responsive (P + D), and cases with fulminant dementia whose motor disorder symptoms were L-dopa nonresponsive (P + D/L-dopa non-responsive). NE neurons were demonstrated by immunocytochemistry against tyrosine hydroxylase (TH). Quantitations of neuronal parameters and cell numbers and three-dimensional reconstructions of the LC were carried out with a computer-assisted system. In SDAT cases, the rostrocaudal LC length (13 +/- 2.2 mm) is shorter than in controls (14.9 +/- 1.4 mm). The four basic LC neuron classes found in the normal human brain (large multipolar, large "bipolar," small multipolar, and small "bipolar" neurons; Chan-Palay and Asan: J. Comp. Neurol. this issue) are recognizable, but many cell somata are swollen and misshapen with fore-shortened, thick, and less branched dendrites. LC neuron numbers are reduced (between -3.5% and -87.5%). Neuron loss is greatest in the rostral part, less in the middle, and least in the caudal part. In PD cases, the rostrocaudal length (12.4 +/- 1.5 mm) is shorter than in SDAT and controls. The neuronal morphology is more severely altered than in SDAT. The basic neuron classes are hardly distinguishable. Most cell bodies are swollen; they frequently contain Lewy bodies; and the dendrites are short and thin with absent or reduced arborizations. Neuron numbers are more reduced than in SDAT (between -26.4% and -94.4%). Alterations are as severe caudally as rostrally in P - D, and P + D/L-dopa nonresponsive cases. P + D cases are more severely affected rostrally. The presence of depression in SDAT and Parkinson's patients is accompanied by the greatest loss of LC neurons. On the basis of morphological alterations of the TH-immunoreactive neurons, and the degree and topographical distribution of neuron loss, a differentiation is possible between the LC in normal brain and that in SDAT and PD for diagnostic purposes.

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 quantitative study of the morphology and distribution of norepinephrinergic neurons in the human locus coeruleus (LC) is given for normal young and older adult brain. Norepinephrine (NE)-producing neurons are identified by immunocytochemistry of two NE biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), visualized by the peroxidase-antiperoxidase and immunogold-silver-staining methods. TH and DBH immunoreactions yield equivalent results. Both immunocytochemical visualization methods allow detailed analysis of neuronal morphology. The neurons of the human LC fall into four classes: large multipolar neurons with round or multiangular somata, large elliptical "bipolar" neurons, small multipolar neurons, and small ovoid "bipolar" neurons. Though most of the neurons contain neuromelanin pigment, some larger neurons lack pigmentation. Dendritic arborization of all neurons is extensive. Computer-assisted quantitative measurements of the parameters somatic size, dendritic arbor length, surface area, and volume are given. Somatic areas of LC neurons of all four classes are decreased in older adult brain, but dendritic arborization is equally extensive as in the younger. The rostrocaudal length of the LC is approximately 15 mm, and no age-dependent decrease is observed. Computer-assisted mapping of immunoreactive neurons and three-dimensional reconstruction allow division of the LC into rostral, middle, and caudal parts with characteristic distribution of neurons. Small neurons predominate in all parts, but the relative contribution of larger cells decreases in a rostrocaudal direction. A cell loss of 27-37% occurs in older adult brains and to 55% in the brain of a chronically depressed patient without dementia. Cell loss is highest in the rostral part, lower in the middle, and absent in the caudal part, and more small cells are lost than larger ones.

Injections of the fluorescent dyes Fast Blue or Granular Blue into either the hippocampus (volume approximately 50 nl) or the entorhinal area (100-150 nl) resulted in labeling by retrograde axonal transport of cells in the diagonal band of Broca (dbB) and the medial septum (MS). A large number (approximately 30%) of these cells contained glutamic acid decarboxylase (GAD)-like immunoreactivity, as determined by combined retrograde fluorescent tracing and GAD-immunohistochemistry. Not all GAD positive cells in the dbB and MS were labeled by fluorochromes in a single experiment. The GAD-stained and fluorochrome-containing cells were present at all rostro-caudal levels of the septum and appeared not to belong to any single morphological class of cells. Double staining experiments showed that the GAD-positive cells did not contain acetylcholinesterase reaction product. These findings provide evidence that a significant portion of the septo-hippocampal projection may utilize gamma-aminobutyric acid as a neurotransmitter.