Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology.

The cleavage of APP by BACE initiates the amyloidogenic process in Alzheimer's disease (AD). We have generated transgenic mice expressing BACE and double transgenic mice expressing BACE and the Swedish mutations of APP (SwAPP) in neurons. BACE transgenic mice did not develop beta-amyloid plaques by age of 14 months, but showed intracellular beta-amyloid immunoreactivity that was co-localized with transgenic BACE in neurons. Abeta levels were increased and AD-like pathology was accelerated in double transgenic mice expressing both BACE and SwAPP. At two months of age, early signs of extracellular Abeta deposition and reactive astrocytes were found in double transgenic, but not in single transgenic mice. Furthermore, at four months, well defined beta-amyloid deposits surrounded by activated astrocytes could be detected in the double transgenic mice. We suggest that BACE overexpression is not sufficient to produce beta-amyloid plaques, but simultaneous expression of BACE and its substrate (SwAPP) leads to an accelerated amyloid plaque formation.

Cell types of the auditory caudomedial neostriatum of the starling (Sturnus vulgaris).

Cell types of the auditory neostriatum in the starling forebrain are described. This area in the caudal neostriatum is defined neurophysiologically by the appearance of auditory neurons. Through use of the rapid Golgi technique, four types of neurons are identified, mainly on the basis of their processes: Neurons with long descending axons and thick dendrites rich in spines (type 1), neurons with long ascending axons and thin dendrites poor in spines (type 2), short-axon neurons (type 3), and microneurons (type 4). The axons of the long neurons pass outside the confines of the auditory neostriatum. Among neurons of type 1; some of the long descending axons directed toward the lower brain centers enter the capsula interna occipitalis (CIO). The descending axons give off many collaterals within the auditory neostriatum. With neurons of type 2; most of the ascending axons cross the lamina hyperstriatica, enter the hyperstriatum ventrale, and arborize near its periventricular region. Some of the long ascending axons reach the overlying hyperstriatum ventrale, pars caudale (HVc, the vocal control area). Among neurons of types 3 and 4; the axons of short-axon neurons and of microneurons end with fine branches within the auditory neostriatum. The dendrites of long-axon neurons are oriented in specific directions, whereas those of short-axon neurons and of microneurons do not show a definite pattern of orientation. In the region of the auditory neostriatum that lies immediately adjacent to the midline of the brain, the first three types of neurons are arranged around the central core known as field L, which is composed of the microneurons and the terminal ramifications of auditory afferents. Laterally the microneurons, along with the fibers of the input tract, undergo a rostral shift to occupy a more peripheral position within the auditory neostriatum. The neurons of the auditory neostriatum are compared with those of the mammalian auditory cortex, and a functional classification of nerve cells into projection neurons, association neurons, and interneurons is proposed.

Morphology of neurons in the lateral geniculate nucleus of the monkey. A Golgi study.

Rapid Golgi preparations of the lateral geniculate nucleus of old- and new-world monkeys were analysed in an attempt to classify the neuronal types. Four main types are described. The commonest, the multipolar neurons, are found in all laminae. Their somata can be large, medium or small and bear dendrites with sparse spines. Some have a "radiate" dendritic arbor and others have dendrites grouped in "tufts". The next most frequent class is of bipolar neurons with two thick dendrites arising from opposite poles of the soma, which is usually large. Otherwise the dendrites are similar to those of multipolar neurons. Relatively rare is a class of medium-sized neurons with beaded dendrites, found here only in magnocellular laminae. There is a fourth class of small neurons distinguished by fine "axon-like" dendritic processes. They are in all laminae and form two subgroups, one with very long, cylindrical dendrites and few axon-like proceses, the other with shorter dendritic arbors and many axon-like processes. In addition, a class of capsular neurons is found in the circumgeniculate capsule between layer 6 and the pregeniculate nucleus. They are large neurons with "umbrella-like" dendritic arbors sending ramifications into layer 6. The interlaminar zones contain scattered somata of all types except beaded and capsular neurons.

Golgi studies of the normal development of neurons in the lateral geniculate nucleus of the monkey.

The development of the morphological features of neurons in the lateral geniculate nucleus of monkeys from the late foetus to the age of one month was studied in rapid Golgi preparations. Most of the neuronal types found in the adult are already recognizable at birth. They differ from their mature forms mainly in having dilatations along their dendrites (growth cones or buds), and a large number of spiny or hair-like processes on their dendrites and somata. During postnatal maturation, first the growth cones and buds regress. Then the number of spines and hairs increases, before decreasing again to reach adult values at around one month. All the main neuronal types follow a similar sequence of maturation, but neurons in magnocellular laminae mature before those in parvocellular. These maturational stages take place during a period of overall growth in cell body size and dendritic length, during which spatial resolution of the neurons is increasing, and when the animal is most susceptible to the effects of visual deprivation.

Frequency of mast cells in the olfactory mucosa of rhesus monkeys.

During studies of the olfactory mucosa and its response to the different levels of circulating sex hormones, considerable numbers of mast cells have been observed in its epithelia and subepithelial regions. The number of these cells in the olfactory mucosa of male monkeys differs greatly from that found in females. The frequency of these cells in the olfactory mucosa of females fluctuates significantly during the menstrual cycle. These fluctations stimultaneously correspond to the well known changes in olfactory sensitivity: around ovulation, when the olfactory sensitivity for certain odorants is high, the number of mast cells in the olfactory mucosa also increases.

Neuronal arrangement in the auditory field L of the neostriatum of the starling.

Light microscopic investigations show that nerve cells of the field L in the starling neostriatum are dispersed into small groups forming unit-like clusters. Isolated neurons occur between these neuronal clusters. Electron microsceopy demonstrates that the neurons occurring in small clusters are not separated by intervening glial processes, but only by a normal intercellular space. In each neuronal cluster large areas of direct somato-somatic and dendro-somatic appositions exist. In areas of somato-somatic apposition, the plasma membranes of adjoining neurons show specialized junctional zones. These junctional zones resemble desmosoid puncta adhaerentia. In areas of dendro-somatic apposition the neuronal plasma membranes approach each other more closely, but do not show any specialized junctional zone. The clustering of neurons without glial separation and the presence of junctional zones between these neurons are discussed.

Surface morphology in the ofactory epithelium of normal male and female rhesus monkeys.

Olfactory epithelium of male and female rhesus monkeys has been studied by transmission electron microscopy. It is shown that the epithelial surface differs greatly between male and female monkeys. Differences are most prominent between male and preovulatory females. During the ovulatory phase of the ovarian cycle remarkable histological alterations occur especially in the sustentacular cells. These alterations are correlated with physiological and behavioral phenomena demonstrating a possible structural basis for the changes in olfactory threshold in relation to sex hormones.