Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain.

All giant neurons of the medial basal forebrain stained for choline acetyltransferase (ChAT). Cell numbers declined from 400,000 to 475,000 in young controls to approximately 140,000 in elderly controls. Five senile dementia cases had counts ranging from 45,000 to 100,000 cells.

Substantia nigra cell death from kainic acid or folic acid injections into the pontine tegmentum.

Injections of kainic acid into the rostral pontine tegmentum in rats caused not only local lesions but destruction of GABAergic and dopaminergic cells in the substantia nigra (SN), as indicated histologically and by measurements of tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). Injections of folic acid caused the nigral damage without local lesions. Pretreatment with scopolamine prevented the losses in GAD without affecting those in TH.

Neurotransmitters in the basal ganglia.

The literature is reviewed on the afferents and efferents of the caudate/putamen, globus pallidus and substantia nigra, and on the neurotransmitters occurring in the various tracts. Emphasis is placed upon the diverse roles played by GABA and glutamate as transmitters in motor pathways and upon the probability that the substantia nigra pars reticulata plays a pivotal role in the output of the basal ganglia. Excessive stimulation of the projection from the pedunculopontine tegmental area to the substantia nigra is shown to cause destruction of dopaminergic neurons in the latter nucleus, suggesting another possible mechanism for cell death in Parkinson's disease.

Sodium-independent glutamic acid binding in cultured fibroblasts from patients with Huntington's disease.

Glutamic acid, in the absence of sodium, binds to a single population of binding sites in the fibroblast membrane with a dissociation constant (K(d)) in the nanomolar range, similar to those obtained in human and rat cortices. The density of binding sites (B(max)) in fibroblast membranes from patients with Huntington's disease was only 54% of that in control membranes.

Neocortical substance P neurons in the baboon: an immunohistochemical finding.

Substance P-like immunoreactive (SP-LI) neurons have been demonstrated, by an avidin-biotin immunohistochemical method, in several neocortical areas in the brains of baboons. These neurons are mostly small in size, and are of many different somatic shapes, including bipolar and multipolar types. They occur in laminae III-VI but are most common in laminae V and VI.

Anti-human choline acetyltransferase fragments antigen binding (FAB)-sepharose chromatography for enzyme purification.

Fragments Antigen Binding (FAB)-Sepharose immunoaffinity chromatography was successfully applied to the purification of human choline acetyltransferase. The mild elution conditions made it possible to obtain the enzyme in its full catalytic state. The method should be generally applicable to enzyme purification.

Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry.

A simple enzyme histochemical technique is described that detects various distinct populations of neurons in the brain. These neurons contain an extremely high activity of an endogenous enzyme, NADPH-diaphorase, that can reduce the dye nitro blue tetrazolium to a bright blue reaction product. Some of the major groups of neurons detected by this technique occur scattered throughout the neocortex, in the striatum and in the laterodorsal tegmental nucleus.

Distribution of GABA-T-intensive neurons in the rat forebrain and midbrain.

The neuronal distribution of gamma-aminobutyric acid (GABA) transaminase (GABA-T), the enzyme which metabolizes GABA, has been mapped in rat brain. The method involves staining for newly synthesized GABA-T by the previously established nitro blue tetrazolium technique in animals killed 8-48 hours after administration of gabaculine, an irreversible inhibitor of GABA-T. Neuronal staining is obscured by staining of other elements if initial suppression is inadequate or survival times postgabaculine are too long.

Changes in muscarinic binding in distant brain regions showing neuronal losses after folic acid injections into the substantia innominata.

Injection of folic acid (FA) into the nucleus substantia innominata (NSI) was found to decrease [3H]quinuclidinyl benzilate ([3H]QNB) binding in the frontal cortex, pyriform cortex, amygdala, and the NSI itself without changing the KD. Binding in the thalamus, caudate nucleus, hippocampus, and substantia nigra was not affected. [3H]Flunitrazepam binding was unchanged in all eight regions studied.

Lipid peroxide distribution in brain and the effect of hyperbaric oxygen.

Regional differences in peroxide levels in rat brain are relatively small but the highest levels were found in the substantia nigra. Lipid peroxides of rat whole brain were significantly increased (22%) immediately after exposure to oxygen at high pressure (OHP). However, this increase was transient.

Choline acetyltransferase immunohistochemistry in brains of Alzheimer's disease patients and controls.

Choline acetyltransferase (ChAT)-containing neuronal structures of the basal forebrain were studied by ChAT immunohistochemistry in the brains of persons dying with Alzheimer's disease (SDAT), as well as age-matched controls dying without neurological disorder. A loss of greater than 50% in ChAT-containing neurons was found in the substantia innominata in the SDAT group. In contrast, there was no reduction in the number of ChAT-containing neurons of the putamen as compared with controls.

Evidence for an intracerebellar acetylcholinesterase-rich but probably non-cholinergic flocculo-nodular projection in the rat.

A combination of a retrograde fluorescent dye tracing technique and staining for acetylcholinesterase (AChE) after di-isopropyl-phosphorofluoridate (DFP) pretreatment was used to identify cells which project to the nodulus, flocculus or cerebellar hemisphere. Spindle-shaped AChE-rich cells in the floccular stalk project to the flocculus, nodulus and uvula, but not to the cerebellar hemispheres. Bilateral removal of the flocculi and paraflocculi, however, decreased significantly only AChE, and not choline acetyltransferase, in nodulus or uvula.

A possible relationship between folic acid neurotoxicity and cholinergic receptors in the pyriform cortex and amygdala.

The substantia innominata complex (SI) is the major source of cholinergic innervation to the amygdala, entorhinal and pyriform cortices, and the neocortex. Immunohistochemical studies using both monoclonal and polyclonal antibodies to choline acetyltransferase (ChAT) have clearly identified that the large size neurons of this area are cholinergic. We have lesioned this area by three methods: electrocoagulation, kainic acid (KA) injection and folic acid (FA) injection.

GABA-transaminase in the basal ganglia: a pharmacohistochemical study.

A pharmacohistochemical procedure to demonstrate histochemically those cells with the ability to synthesize the GABA-metabolizing enzyme GABA-transaminase has been applied to determine the localization of this enzyme in the basal ganglia. In normal, pharmacologically unmanipulated animals, strong GABA-transaminase activity is present throughout the neuropil in many nuclei of the basal ganglia. The striatum, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra are all heavily stained.

Cross-reactivity of antibodies to chicken brain choline acetyltransferase with mammalian enzyme.

An antiserum was obtained from immunized rabbit after 3 subcutaneous injections of 100 micrograms each of a purified chicken choline acetyltransferase (ChAT) preparation, which had a specific activity of 2.32 mumol acetylcholine formed/min/mg protein. The antiserum or immunoglobulins strongly inhibited ChAt activities from chicken and mammalian brains in immunoprecipitation experiments.

A histochemical study of GABA-transaminase in the efferents of the pallidum.

Kainic acid lesions of the globus pallidus reduce the histochemically detectable GABA-transaminase activity in the ipsilateral subthalamic nucleus. A similar decrease in enzyme activity occurs in the lateral habenula following lesions of the entopeduncular nucleus. Previous results on the localization of GABA-transaminase in efferents of the striatum indicated that such histochemistry may be a useful adjunct for the demonstration of GABA pathways.

Cholinergic projections from the basal forebrain of rat to the amygdala.

Cholinergic afferents to the amygdala from the basal forebrain were studied using di-isopropyl fluorophosphate-AChE histochemistry in combination with retrograde tracing using various fluorescent dyes. Cells sending their axons to the amygdala and staining intensely for AChE were located mainly in the nucleus of the substantia innominata. They also were found in the ventral part of the globus pallidus, the horizontal limb of the nucleus tractus diagonalis Broca, and the nucleus interstitialis ansae lenticularis.

Ornithine aminotransferase in Huntington's disease.

Ornithine aminotransferase (Orn-T) activities in Huntington's disease (HD) brains were found to be reduced, when compared to age-matched control brains, by 34-49% in the frontal cortex, parietal cortex, caudate nucleus and putamen. Such changes were not observed in senile dementia of Alzheimer type or schizophrenia. Alterations in choline acetyltransferase activities were consistent with previous findings for these disorders.

Lipid peroxides in brain during aging and vitamin E deficiency: possible relations to changes in neurotransmitter indices.

Lipid peroxide levels, were found to be significantly higher in brains of 18 month old as compared to 4 month old rats, with particularly large increases occurring in the olfactory bulb, globus pallidus, cerebral cortex and caudate-putamen (CP). Eighteen month old rats fed a vitamin E deficient diet for 9 months before sacrifice had lipid peroxide levels significantly higher than age-matched controls in the cerebral cortex, hippocampus and hypothalamus. Age-related decreases were seen in choline acetyltransferase, acetylcholinesterase and 3H-QNB binding in some but not all brain regions, while GABA transaminase and MAO showed age-related increases.