Biomedical subjects

Z Henderson

Publications and source records attributed to Z Henderson.

At least 37 records · Page 2Linked to original sources

PubMed1998

Density of choline acetyltransferase-immunoreactive terminals in the rat dentate gyrus after entorhinal cortex lesions: a quantitative light microscope study.

Lesion of the entorhinal cortex in the adult rat is a model for Alzheimer's disease and produces a marked increase in acetylcholinesterase (AChE) activity in the outer molecular layer (OML) of the dentate gyrus. This has been attributed to the sprouting of cholinergic axons terminals in response to denervation of the OML. The aim of this study was to investigate the density changes of cholinergic terminals in the OML at the light microscope level by using choline acetyltransferase (ChAT) immunohistochemistry and quantitative analysis. The results showed that between days 10 and 33 after an entorhinal cortex lesion, there was a measurable increase in the density of ChAT-positive boutons in the OML of the ipsilateral dentate gyrus (x1.2-1.6 of contralateral). However, when shrinkage of the ipsilateral OML (x0.5-0.75 of contralateral) was taken into account, the apparent increase in ChAT terminal density was entirely accounted for by shrinkage of the OML. Thus ChAT immunohistochemistry at the light microscope level provides no positive evidence for a proliferation of cholinergic terminals in the entorhinal cortex lesion model. This is in agreement with previous biochemical assays that have shown no change of total ChAT activity in the dentate gyrus after entorhinal cortex lesions.

Acetylcholinesterase↗

PubMed1997

Galanin-immunoreactive synaptic terminals on basal forebrain cholinergic neurons in the rat.

Previous studies have indicated that galanin is one of the most abundant peptides in the basal forebrain and that it has a significant modulatory influence on cholinergic transmission. The aim of the present study was to use a light electron microscopic correlation technique to determine whether galanin-immunoreactive terminals form synaptic contacts with basal forebrain cholinergic cells of the rat. Sections from fixed-perfused brains were stained at the light and electron microscopic levels for galanin and choline acetyltransferase immunoreactivity in the same section by using a dual-colour immunohistochemical method. The results showed that galanin-immunoreactive axonal terminals are unevenly distributed in the medial septal nucleus, the diagonal band, and the nucleus basalis. Galanin-positive synapses were most prominent on choline acetyltransferase-positive neurons in the lateral parts of the nucleus of the diagonal band and in the posterior half of the nucleus basalis, which is where there was the greatest overlap between the distribution of galanin-immunoreactive terminals and choline acetyltransferase-positive neurons. The origins of these galanin-positive terminals are not known, but the results confirm that the basal forebrain galaninergic system has a synaptic influence on basal forebrain cholinergic neurons in the rat.

Animals↗

PubMed1997

The projection from the striatum to the nucleus basalis in the rat: an electron microscopic study.

Previous studies have shown that the striatum provides synaptic inputs to the globus pallidus and entopeduncular nucleus in which GABA is co-localized with the peptides enkephalin and substance P. The aim of this study in the rat was to determine whether the striatal projections also make synaptic contact with the cholinergic neurons of the nucleus basalis, which lie near to the pallidal areas in the rat brain. The anterograde tracer biocytin was injected into different parts of the striatum, and brain sections were stained for biocytin and choline acetyltransferase immunoreactivity by using a dual colour method. Terminals labelled with biocytin by anterograde transport and which made synaptic contact with choline acetyltransferase-positive soma and dendrites were identified by light-electron microscopic correlation methods. In the cases where the biocytin injections had been made in the dorsal or lateral striatum, biocytin-labelled terminals made synaptic contact with cholinergic cells in the region between the main termination zones in the globus pallidus and the entopeduncular nucleus. In the cases where the injections had been made in the ventromedial and posterior striatum, there was greater overlap between choline acetyltransferase-positive structures and biocytin-labelled terminals in the main termination zones in the globus pallidus or entopeduncular nucleus, but relatively few of these terminals made synaptic contacts on to the cholinergic neurons. The results therefore indicate that the cholinergic nucleus basalis cells receive a relatively sparse synaptic input from all parts of the striatum. It has recently been shown that the cholinergic cells of the nucleus basalis selectively express high levels of substance P and opioid receptor messenger RNAs, while the non-cholinergic pallidal cells have much higher levels of GABA(A) receptor subunit messenger RNAs. It is concluded that the cholinergic neurons of the nucleus basalis in the rat may be selectively responsive to the peptidergic components of the striatal outputs, and that they are most likely to be influenced by both the limbic and sensorimotor parts of the striatum.

Acetylcholinesterase↗

PubMed1996

Responses of basal forebrain cholinergic neurons to damage in the adult brain.

The basal forebrain cholinergic system, which projects to all cortical areas, is a good model for the study of the responses of central nervous system (CNS) neurons to injury. Much is known about the specific neurotrophic factors of basal forebrain cholinergic neurons, and there are many techniques available to chart the progress of degeneration and recovery of cholinergic neurons after damage. There is also a clinical version of damage to cholinergic neurons which is part of the selective pathology of Alzheimer's disease. In general, CNS neurons do not regenerate well after brain damage. The first part of the review describes how the CNS promotes only limited neuronal regeneration, and that this is because of the presence of inhibitory factors and the lack of growth factors. Despite this, some CNS areas may provide a better environment for CNS regeneration than others. In the second part of the review, the degeneration and regeneration of basal forebrain cholinergic pathways in the adult rat are discussed. It is shown how the collateral sprouting of cholinergic axons occur more readily in the hippocampal formation than in neocortical areas, and that this could be linked with the more neuroplastic properties of the hippocampus. The third part of the review describes how the degeneration of cholinergic pathways in Alzheimer's disease is likely to be secondary to the pathology or degeneration of certain cortical areas. The hypothesis is put forward that the severity of the pathology in highly plastic limbic cortical areas could be linked with their susceptibility to risk factors of Alzheimer's disease such as ageing, and genetic and environmental factors.

Adult↗

PubMed1995

Expression of GABAA receptor subunit messenger RNA in non-cholinergic neurons of the rat basal forebrain.

A previous in situ hybridization study by Wisden et al., J. Neurosci. 12, 1040-1062, showed a high expression of the GABAA receptor alpha 1, beta 2 and gamma 2 subunit messenger RNAs in the medial septal nucleus and nucleus of the diagonal band of the rat. The aim of the present study was to determine whether this high expression of GABAA receptor subunit messenger RNAs is found in the cholinergic neurons of these areas. Adjacent 4-5 microns sections of rat forebrain were submitted to choline acetyltransferase immunocytochemistry or to in situ hybridization histochemistry using oligonucleotides complementary to parts of the GABAA receptor alpha 1, alpha 2, beta 2, delta 1 and gamma 2 subunit messenger RNAs. It was found that the high expression for the GABAA receptor alpha 1, beta 2 and gamma 2 subunit messenger RNAs in the medial septal nucleus, the nucleus of the diagonal band and the nucleus basalis is located almost exclusively in non-cholinergic neurons. It was also found that these non-cholinergic cells are also continuous in distribution with neurons in the globus pallidus and ventral pallidum that similarly express high levels of messenger RNA for the GABAA receptor alpha 1, beta 2 and gamma 2 subunits. It was concluded that the basal forebrain cholinergic neurons may not be as sensitive to GABAA receptor influences as their non-cholinergic neighbours.

Animals↗

PubMed1994

The paragigantocellular nucleus of the ventral medulla: a secondary source of cholinergic innervation of rat brainstem nuclei.

Many parts of the brainstem are known to be innervated by the cholinergic neurons of the pontomesencephalic tegmentum, but other possible sources of this innervation have rarely been considered. We sought to examine whether other cells in the brainstem were responsible for this cholinergic input using axonal tract tracing and choline acetyltransferase (ChAT) immunocytochemistry. The results confirm previous studies on the projections of the neurons of the pontomesencephalic tegmentum but also show that a group of ChAT-positive cells in the paragigantocellular nucleus in the ventral medulla are a source of widespread, albeit less substantial cholinergic projections to several areas of the brainstem.

Animals↗

PubMed1994

A cholinergic propriospinal innervation of the rat spinal cord.

Previous work has suggested the presence of a widespread, intrinsic cholinergic innervation of the spinal cord. A combination of retrograde axonal tract tracing and choline acetyltransferase immunocytochemistry was used to show that there is a propriospinal cholinergic innervation of the rat spinal cord that arises from short-range projections (spanning up to six spinal segments) of cholinergic neurons known as 'central canal' and 'partition' cells.

Acetylcholine↗

PubMed1994

Cholinergic neurons in the ventral trapezoid nucleus project to the cochlear nuclei in the rat.

A combination of retrograde axonal tract tracing and choline acetyltransferase immunocytochemistry was used to determine the cells of origin of the cholinergic innervation of the rat cochlear nucleus. The results showed that the cochlear nucleus receives a major cholinergic input from a group of small cells found in the ventral trapezoid nucleus. Experiments using an anterograde tracer confirmed the presence of a neuronal pathway from the ventral trapezoid nucleus to the cochlear nucleus and showed that this pathway travels via the trapezoid body.

Animals↗

PubMed1993

The effects of monocular enucleation on ganglion cell number and terminal distribution in the ferret's retinal pathway.

Anterograde and retrograde tracing techniques were used to examine the effects of removing one eye at birth on the remaining uncrossed retinal pathway in adult ferrets. After enucleation, the adult number of labelled ganglion cells projecting ipsilaterally changed from an average of 6068 in normal pigmented ferrets to an average of 7813 (29% increase) in pigmented enucleates. The change in albino ferrets was from 1455 in normals to 2319 in enucleates (59% increase). Labelled cells scattered across nasal retina accounted for over half the increase in the uncrossed population. After neonatal enucleation, the volume of lateral geniculate nucleus occupied by the uncrossed projection increased substantially: five-fold in pigmented animals and 20-fold in albinos. These results suggest that neonatal removal of one eye has a greater effect on the distribution of uncrossed terminals than on the survival of uncrossed ganglion cells. There was also an increase in the total number of axons in the surviving optic nerve of both pigmented and albino ferrets (93,000 in enucleates compared with 79,000 in normal animals), which cannot be simply explained as a disruption of binocular competition.

Albinism↗

PubMed1991

Organisation of the visceral solitary tract nucleus in the ferret as defined by the distribution of choline acetyltransferase and nerve growth factor receptor immunoreactivity.

The cholinergic innervation of the visceral component of the nucleus of the solitary tract in the ferret was investigated by using choline acetyltransferase immunocytochemistry. The subdivisions of the ferret solitary tract nucleus as defined by Nissl architectonics were found to correspond to most of those previously assigned to the cat solitary tract nucleus. The subnuclei of the ferret solitary tract nucleus were also outlined by using immunohistochemical and histochemical methods to stain for nerve growth factor (NGF) receptor and acetylcholinesterase, respectively. In particular, the gelatinosus and interstitial subnuclei stain intensely for NGF receptor immunoreactivity and for acetylcholinesterase activity. Since abundant NGF receptor immunoreactivity is observed also in the nodose ganglion and in the solitary tract, it was assumed that the gelatinosus and the interstitial subnuclei represent the principal sites of termination of primary visceral afferents. A rich choline acetyltransferase-positive terminal axonal arborization was located in all of the subdivisions of the solitary tract nucleus but was found to be lacking in the gelatinosus and interstitial subnuclei. A small number of giant choline acetyltransferase-positive axon terminals was seen in the subnucleus gelatinosus but was assumed to be of doubtful functional significance because these terminals derive from only one or two large axons on each side of the brain. The weak cholinergic innervation of the gelatinosus and interstitial subnuclei and the stronger innervation of the other subnuclei suggest that acetylcholine has a more important role in the secondary rather than the primary processing of afferent visceral information. Because the distribution of acetylcholinesterase activity in the nucleus of the solitary tract matches that of the NGF receptor immunoreactivity rather than that of the cholinergic acetyltransferase immunoreactivity, a non-cholinergic function for acetylcholinesterase may dominate in the solitary tract nucleus of the ferret.

Animals↗

PubMed1991

Distribution of choline acetyltransferase immunoreactive axons and terminals in the rat and ferret brainstem.

A survey was made of the density of the cholinergic innervation of different parts of the brainstem of the rat and ferret. Sections of rat and ferret brainstems were stained for choline acetyltransferase (ChAT) immunoreactivity by using a sensitive immunocytochemical method. Adjacent sections were stained for acetylcholinesterase activity or Nissl substance. The density of the distribution of fine calibre, varicose ChAT-positive axons, assumed to represent cholinergic terminals, was categorised arbitrarily into high, medium, or low. A high density of ChAT-positive terminals was found in all or parts of these structures: interpeduncular nucleus, superficial grey layer of the superior colliculus (ferret), intermediate layers of the superior colliculus, lateral part of the central grey (rat), an area medial to the parabigeminal nucleus (rat), pontine nuclei, ventral tegmental nucleus (rat), midline pontine reticular formation, and an area ventral to the exit point of the 5th nerve (ferret). A medium density of ChAT-positive terminals was observed in all or parts of: the substantia nigra zona compacta (ferret), ventral tegmental area (ferret), superficial grey layer of the superior colliculus, intermediate and deep layers of the superior colliculus, lateral central grey, area medial to the parabigeminal nucleus, inferior colliculus, dorsal tegmental nucleus, ventral tegmental nucleus (ferret), pontine nuclei, ventral nucleus of the lateral lemniscus (ferret), midline pontine reticular formation, ventral cochlear nucleus, dorsal cochlear nucleus, lateral superior olive, spinal trigeminal nuclei, prepositus hypoglossal nucleus, lateral reticular nucleus, paragigantocellular nucleus, and the dorsal column nuclei including the cuneate, external cuneate, and gracile nuclei. A low density of ChAT-positive terminals was seen throughout the remainder of the brainstem of the rat and ferret, but these terminals were absent from the medial superior olive, substantia nigra zona reticulata (rat), and the central part of the ferret lateral superior olive. A pericellular-like distribution of ChAT-positive terminals was observed in the ventral cochlear nucleus and in association with some of the cells of the nucleus of the mesencephalic tract of the trigeminal nerve. A climbing fibre type arrangement of ChAT-positive terminals was found in the substantia nigra zona compacta (ferret) and medial reticular formation. In general, the distribution of staining for AChE activity reflected that of the distribution of ChAT immunoreactivity in the brainstem, except in a few regions where there were also species differences in the distribution of ChAT-positive terminals, e.g., in the superficial grey layer of the superior colliculus and in the substantia nigra.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Further evidence for the absence of a descending cholinergic projection from the brainstem to the spinal cord in the rat.

Serotonergic and catecholaminergic neurons are known to project from the brainstem to the spinal cord. However, evidence for a bulbo-spinal projection that is cholinergic is sparse despite immunocytochemical and physiological evidence for a cholinergic influence on the cord. In this study we examined the possibility of a direct cholinergic bulbo-spinal projection in the rat using a combination of retrograde axonal tracing techniques and choline acetyltransferase immunocytochemistry. Although many cells were found to project to the cord from the brainstem, none were identified as being cholinergic, confirming previous evidence that the cholinergic innervation of the cord is intrinsic.

Animals↗

PubMed1991

Presence of a cholinergic projection from ventral striatum to amygdala that is not immunoreactive for NGF receptor.

By combining the retrograde axonal transport of a fluorescent dye with nerve growth factor (NGF) receptor or choline acetyltransferase (ChAT) immunocytochemistry, we show that the cholinergic neurons that project most strongly to the basolateral nucleus of the amygdala in the ferret do not possess NGF receptor immunoreactivity in their soma and are situated in the ventral striatum, an area known to receive a massive reciprocal projection from the basolateral nucleus of the amygdala.

Amygdala↗

PubMed1991

Is nerve growth factor required for the survival of retinal ganglion cells during development?

Staining for nerve growth factor receptor was observed in the ferret's retinal ganglion cell layer, optic nerve and tract, and in the lateral geniculate nucleus and superficial layers of the superior colliculus in the prenatal period, but had disappeared by birth. Thus the incidence of this transient staining does not correspond with the ganglion cell death that is known to occur in the ferret retina during the first postnatal week.

Animals↗

PubMed1991

Early development of the nucleus basalis-cortical projection but late expression of its cholinergic function.

The aim of this study was to examine the development of the basalocortical pathway by using choline acetyltransferase and nerve growth factor receptor immunocytochemistry, acetylcholinesterase histochemistry and retrograde axonal transport. The observations were made in the ferret because in this species brain development occurs over a much more protracted period than in the rat. Staining for choline acetyltransferase immunoreactivity in the brain was minimal before birth. Adult levels of staining for the enzyme were not seen in cell bodies until three weeks after birth and in axons up to six weeks after birth. This, however, did not mean that presumptive cholinergic pathways are absent early in development. There was strong staining for nerve growth factor receptor in basal forebrain neurons from at least two weeks before birth. Positive staining for acetylcholinesterase was found in axons that begin to invade the cerebral cortex a week before birth. The retrograde axonal transport technique showed that the basalocortical pathway has a normal organization in the neonate. The conclusion is that cholinergic pathways form early in the prenatal period in the ferret but express their transmitter function late in postnatal development.

Acetylcholinesterase↗

PubMed1991

Sprouting of cholinergic axons does not occur in the cerebral cortex after nucleus basalis lesions.

Different doses of the excitotoxin quisqualate were used to make lesions in the caudal part of the ferret nucleus basalis, i.e. the part that projects to the visual cortex. The higher doses of the excitotoxin destroyed all nerve growth factor receptor-immunoreactive cells in the caudal nucleus basalis and gave rise to up to 75% loss of acetylcholinesterase-containing axons in the visual cortex. In sections stained for Nissl substance there was generalized tissue damage around the injection sites and extensive loss of all neuron types in areas surrounding the caudal nucleus basalis. Lower doses of the excitotoxin damaged only a proportion of the nerve growth factor receptor-immunoreactive neurons in the caudal nucleus basalis and produced a much lower depletion of acetylcholinesterase-positive fibres in the visual cortex. The only damage seen in sections stained for Nissl substance was a loss of magnocellular neurons in the vicinity of the injection sites. A quantitative morphological approach was used to show that either one week or three months after the lesions there was a linear correlation between the proportion of acetylcholinesterase-positive axons lost in the visual cortex and the proportion of nerve growth factor receptor-immunoreactive cells that had disappeared from the caudal nucleus basalis. Since the correlation lines for the short-term (one week) survival and the long-term (three months) survival experiments coincided, this indicated that no collateral sprouting of cholinergic axons had occurred in the visual cortex of the long-term survival animals regardless of size of the lesion in the nucleus basalis.

Acetylcholinesterase↗

PubMed1991

Cholinergic input to dopaminergic neurons in the substantia nigra: a double immunocytochemical study.

In order to determine whether the cholinergic fibres that innervate the substantia nigra make synaptic contact with dopaminergic neurons of the substantia nigra pars compacta, a double immunocytochemical study was carried out in the rat and ferret. Sections of perfusion-fixed mesencephalon were incubated first to reveal choline acetyltransferase immunoreactivity to label the cholinergic terminals and then tyrosine hydroxylase immunoreactivity to label the dopaminergic neurons. Each antigen was localized using peroxidase reactions but with different chromogens. At the light microscopic level, in confirmation of previous observations, choline acetyltransferase-immunoreactive axons and axonal boutons were found throughout the substantia nigra. The highest density of these axons was found in the pars compacta where they were often seen in close apposition to tyrosine hydroxylase-immunoreactive cell bodies and dendrites. In the ferret where the choline acetyltransferase immunostaining was particularly strong, bundles of immunoreactive fibres were seen to run through the reticulata perpendicular to the pars compacta. These bundles were associated with tyrosine hydroxylase-immunoreactive dendrites that descended into the reticulata. The choline acetyltransferase-immunoreactive fibres made "climbing fibre"-type multiple contacts with the tyrosine hydroxylase positive dendrites. At the electron microscopic level the choline acetyltransferase-immunoreactive axons were seen to give rise to vesicle-filled boutons that formed asymmetrical synaptic specializations with nigral dendrites and perikarya. The synapses were often associated with sub-junctional dense bodies. On many occasions the postsynaptic structures contained the tyrosine hydroxylase immunoreaction product, thus identifying them as dopaminergic. It is concluded that at least one of the synaptic targets of cholinergic terminals in the substantia nigra are the dendrites and perikarya of dopaminergic neurons and that in the ferret at least, the dendrites of dopaminergic neurons that descend into the pars reticulata receive multiple synaptic inputs from individual cholinergic axons.

Animals↗

PubMed1989

The cholinergic input to the superficial layers of the superior colliculus: an ultrastructural immunocytochemical study in the ferret.

The cholinergic innervation of the superficial layers of the ferret's superior colliculus was investigated with a combination of electron microscopy and choline acetyltransferase immunohistochemistry. Cholinergic boutons in the superficial layers of the superior colliculus possess spherical vesicles and make predominantly asymmetrical synapses onto the profiles of small dendrites, as do the terminals of cortical and retinal axons. In most areas of the brain studied so far, cholinergic terminals tend to form synapses of the symmetrical variety.

Animals↗