R.C.A. Pearson

Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer's type demonstrated by immunohistochemical staining for choline acetyltransferase

Immunohistochemically identified cholinergic neurons in the basal nucleus of Meynert in a brain with SDAT have been compared with those in two age- and sex-matched normal brains. The numbers of such cells at carefully matched levels are not significantly lower, but the cells in SDAT are substantially smaller than in the normal basal nucleus. The persistence of shrunken cholinergic neurons in the basal nucleus in the diseased brain is similar to that seen in an experimental study of retrograde cellular degeneration in the nucleus following damage of the cortex.

Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage.

The effects of unilateral cortical damage on immunohistochemically identified cholinergic neurons of the basal nucleus have been examined in the rat. In the first 2 weeks after operation, the cells were swollen and their nuclei became eccentric, these changes being closely similar to those seen in the cholinergic oculomotor nuclei of the same animals following removal of the extraocular muscles. During the third week these acute changes were replaced by shrinkage of the cholinergic cell bodies and their dendrites. At longer survival times the appearance of the neurons did not alter, and all the cholinergic cells persisted in their shrunken form after 120 days, the longest survival time examined.

The cholinergic nuclei of the basal forebrain of the rat: normal structure, development and experimentally induced degeneration

The normal morphology and distribution of the cholinergic neurones of the basal forebrain of the rat have been studied qualitatively and quantitatively after staining immunohistochemically with a monoclonal antibody to choline acetyl transferase (ChAT). This was done in order to provide an adequate control for the changes found in these cells on both sides of the brain in the experimental investigation of the reaction of the cells to damage of their axons. The cholinergic cells form a more or less continuous anteroposterior band, but they can be subdivided into distinct nuclear groups on the basis of the size and form of the cell bodies and dendrites, their position and arrangement. these nuclei conform closely to previous descriptions of Nissl-stained material: the medial septal nucleus, the vertical and horizontal nuclei of the diagonal band and the basal nucleus. Quantitative measurements of the cross-sectional areas of the cells in the different nuclei confirmed the conclusions drawn from the qualitative examination. Measurements of the ChAT cells at different ages showed that in all nuclei they are significantly larger in size in infancy than in the adult, and they shrink to the mature size by 46 days. The cells in the various cholinergic nuclei show distinctly different reactions to damage of their terminal axonal fields. After removal of a large part of the neocortex by removal of the overlying pia-arachnoid mater the cells in the basal nucleus in the operated hemisphere underwent retrograde cellular degeneration, being swollen and paler-staining up to 14 days, and thereafter shrinking by 20-30% (as compared with those in the brains of age- and sex-matched littermate controls). The degree of shrinkage was appreciably greater when the animals were operated upon at the neonate stage. No cell loss was found, qualitatively or quantitatively, in the basal nucleus. After removal of the hippocampus there is marked loss of cholinergic neurones in the medial septal nucleus and in the vertical nucleus of the diagonal band, and with severe shrinkage of the remaining cells. Removal of the olfactory bulb results in only slight shrinkage of the cells, and no cell loss, in the horizontal nucleus of the diagonal band.(ABSTRACT TRUNCATED AT 400 WORDS)

The organization of the connections between the cortex and the claustrum in the monkey.

The distribution of labelled cells and of extracellular granules in the claustrum has been studied after injections of horseradish peroxidase in several areas of the neocortex. The frontal and parietal lobes are related to the anterior and posterior halves respectively of the claustrum, and the occipital and temporal cortex to the posterior and inferior margins. Parts of the claustrum related to areas of the cortex in the frontal lobe overlap considerably in the antero-posterior dimension with parts related to widely separated but interconnected areas of the parieto-temporal cortex. Areas of cortex within one lobe which are interconnected are related to parts of the claustrum which overlap in the dorsoventral dimension.

Retrograde changes in the nucleus basalis of the rat, caused by cortical damage, are prevented by exogenous ganglioside GM1

In rats with extensive unilateral cortical damage, retrograde effects upon the cholinergic cells of the basal nucleus were observed. Cells of the basal nucleus stained immunocytochemically for choline acetyltransferase were shrunken and choline acetyltransferase enzymatic activity in that region was reduced. Both these effects could be prevented by the administration of the ganglioside GM1.

Retrograde cell degeneration in the basal nucleus in monkey and man

Retrograde cellular degeneration has been found in the basal nucleus of Meynert in macaque monkeys after large lesions of the neocortex, and in the human brain after either hemidecortication or leucotomy. These observations may be relevant to the interpretation of the cellular degeneration in the basal nucleus in Alzheimers disease.

The projection of the basal nucleus of Meynert upon the neocortex in the monkey

After injections of horseradish peroxidase into several areas of the neocortex in the macaque monkey longitudinal bands of labeled cells in the basal nucleus of Meynert related to areas of cortex in the frontal lobe have been found to overlap along their long axes with the bands related to widely separated but interconnected areas of the parieto-temporal cortex. The frontal and parietal lobes are related to the anterior and posterior halves respectively of the nucleus, the temporal cortex to the postero-lateral margin of the nucleus and the occipital lobe to its upturned posterior extension.

Degeneration of cholinergic neurons in the basal nucleus following kainic or N-methyl-D-aspartic acid application to the cerebral cortex in the rat

The effect on cholinergic neurons in the basal nucleus of exposing the cortex to excitotoxic amino acids was examined in the rat. Kainic or N-methyl-D-aspartic acid were applied extradurally over the cerebral cortex of one side. This resulted in a severe depletion in the numbers of neurons in the underlying cortex. The immunohistochemically identified cholinergic neurons of the ipsilateral basal nucleus showed a significant shrinkage, -31% of their mean cell area, which was comparable with the retrograde degeneration seen following direct mechanical damage of the cortex. These findings suggest that cholinergic neurons of the basal nucleus can undergo transneuronal retrograde degeneration.

The cortico-cortical connections of area 7b, PF, in the parietal lobe of the monkey

The cortico-cortical connections of area 7b (or PF) in the parietal lobe of the monkey have been studied with the method of axoplasmic transport of horseradish peroxidase or with the method of axonal terminal degeneration. Area 7b is reciprocally and precisely connected with area 5, the second somatic sensory area (SII), area 23 of the cingulate cortex, the retroinsular area (Ri), the granular insular area (Ig), and with the cortex in the walls of the superior temporal sulcus.

Parenterally administered GM1 ganglioside prevents retrograde degeneration of cholinergic cells of the rat basal forebrain.

The effect of daily intraperitoneal injections of GM1 ganglioside on retrograde degeneration in the basal forebrain has been examined, using a monoclonal antibody directed against choline acetyltransferase to identify the cholinergic neurones. Rats underwent extensive damage of the cerebral cortex and underlying hippocampus. From the day of operation on, they received daily injections of ganglioside. After a survival of 30 days, the animals were killed and the cholinergic cells of the basal forebrain were examined. These were compared with material treated in the same way from animals who had received the injections of ganglioside but no lesion, animals who had been operated upon but without the ganglioside treatment, and normal animals. Intraperitoneal ganglioside administration markedly reduces the retrograde death of the cholinergic neurones of the medial septal nucleus and abolishes the shrinkage of the remaining neurones following hippocampal damage.