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M V Sofroniew

Publications and source records attributed to M V Sofroniew.

At least 73 records · Page 4Linked to original sources
PubMed1988

Loss of transmitter-associated enzyme staining following axotomy does not indicate death of brainstem cholinergic neurons.

To assess the validity of using loss of transmitter-associated enzyme staining to document the death of injured cholinergic neurons, vagal and hypoglossal cholinergic neurons were quantitatively identified at 7 and 28 days following unilateral axotomy using staining procedures for choline acetyltransferase (ChAT) or acetylcholinesterase (AChE), using Nissl stains, and using the retrogradely transported dye, True blue, as an intracellular marker. At 7 days post-axotomy, the transmitter-associated enzymes, ChAT and AChE, had disappeared from over 95% of vagal neurons (P greater than 0.001) and from over 50% of hypoglossal neurons (P greater than 0.001) as compared with the unlesioned control side. At 28 days post-axotomy, ChAT and AChE were still absent from over 70% of vagal neurons (P greater than 0.001) but only from about 15% of hypoglossal neurons as compared with unlesioned control sides. In contrast, no statistically significant losses of either vagal or hypoglossal neurons were found at 7 or 28 days post-axotomy using Nissl stains or detection of retrogradely transported True blue. These findings indicate that transmitter-associated enzyme expression can be regulated independently of neuronal survival following injury. We conclude that absence of transmitter-associated enzyme staining is not an absolute indicator of death of cholinergic neurons.

Acetylcholinesterase↗
PubMed1988

Slice cultures of rat hypothalamus examined by immunohistochemical staining for neurohypophyseal peptides and GFAP.

Organotypic cultures were prepared from slices of neonatal rat hypothalami and were immunohistochemically stained for the neurohypophyseal peptides vasopressin and oxytocin, their associated neurophysins, and for glial fibrillary acidic protein (GFAP). Both glial and neural elements survived and matured within the cultures, expressing cellular morphologies and retaining a topographic organization similar to that found in vivo. Neurones producing peptides were readily identified and such peptidergic neurones elaborated processes with an appearance characteristic of beaded axons. These presumptive axons grew in a selective and specific manner over certain regions in the slice cultures while avoiding other regions in a manner similar to that found in vivo. In cocultures of hypothalamus and neurointermediate lobe tissue, peptidergic axons found and grew over the neurointermediate lobe tissue and elaborated extensive terminal arborizations. Thus, it appears that at least some of the cues used for appropriate axonal guidance are maintained in these cultures. Organotypic cultures retain many in vivo characteristics as regards cellular morphology and cellular interactions, yet provide an in vitro environment useful for the study of morphology, physiology, cell biology and neurone-target interaction of hypothalamic neurones.

Animals↗
PubMed1987

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)

Age Factors↗
PubMed1987

The cholinergic nuclei of the basal forebrain of the rat: hypertrophy following contralateral cortical damage or section of the corpus callosum.

After damage of the neocortex of one hemisphere by removal of the pia-arachnoid mater, the cholinergic cells of the basal nucleus of the unoperated hemisphere show a marked increase in their cross-sectional areas. This hypertrophy reaches a maximum of 25% by 3 weeks after operation and persists indefinitely. The cell bodies appear normal in shape, are often paler-staining and the hypertrophy includes the proximal dendrites. The hypertrophy is confined to the part of the basal nucleus corresponding to that which shows shrinkage on the operated side. The enlargement is greatest in animals operated upon on the first day after birth (+31%), is less in adult animals (mean +22%) but occurs at all ages up to 496 days, the oldest animal used. After unilateral removal of the hippocampus or section of the fimbria there is hypertrophy of the cholinergic neurones of the contralateral medial septal nucleus (+24%) and vertical nucleus of the diagonal band (+18%). Removal of the olfactory bulb on one side had no apparent effect upon the cholinergic neurones in the contralateral horizontal nucleus of the diagonal band. Damage of the neocortex by exitotoxic amino acids did not result in hypertrophy of the cholinergic cells of the contralateral basal nucleus despite marked shrinkage of the neurones in the basal nucleus on the operated side. After section of the corpus callosum the neurones throughout the basal nucleus of both sides are significantly larger than in the normal animal; the hypertrophy has occurred by 20 days after operation and persists indefinitely.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Neuropeptide Y, somatostatin, and reduced nicotinamide adenine dinucleotide phosphate diaphorase in the human striatum: a combined immunocytochemical and enzyme histochemical study.

Neuropeptide Y and somatostatin immunoreactive neurons and processes were examined in human striatum using both immunofluorescence and avidin biotin immunoperoxidase methods. Reduced nicotinamide adenine dinucleotide phosphate diaphorase activity was histochemically determined by the reduction of nitro blue tetrazolium. Immunofluorescence using a monoclonal anti-somatostatin antibody and a polyclonal anti-neuropeptide Y antibody, followed by diaphorase histochemistry, showed that these three neurochemical markers are co-localized in a single population of medium-sized aspiny intrinsic neurons. Cells were evenly distributed in clusters throughout the striatum, but fiber density was higher in the nucleus accumbens and ventromedial regions of the caudate and putamen. Double-stained reduced nicotinamide adenine dinucleotide phosphate diaphorase-acetylcholinesterase sections demonstrated that these neurons are located in zones of high acetylcholinesterase activity, often at the interface of these zones with regions of low enzyme activity. These biochemically distinctive neurons are uniquely situated to modulate activity between striatal compartments. Our findings provide new information about the modular organization of the striatum and extend these observations in human brain.

Aged↗
PubMed1986

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.

Animals↗
PubMed1986

Cortical grafts prevent atrophy of cholinergic basal nucleus neurons induced by excitotoxic cortical damage.

Damage to the neocortex, here induced by the excitotoxin kainic acid in the rat, is known to induce cell shrinkage, without actual loss of cells, in the part of the cholinergic basal nucleus projecting to the damaged area. Fetal cortical tissue, implanted into the neuron-depleted cortex in the form of a dissociated cell suspension, completely prevented this degenerative change of the basal nucleus cholinergic neurons. Choline acetyltransferase biochemistry and acetylcholinesterase fiber staining of the transplants indicated a substantial ingrowth from the cholinergic host neurones into the graft. It is proposed that the basal forebrain cholinergic neurons normally receive a trophic influence from their target areas and that grafted neocortex can substitute for the loss of such trophic influence in cortex-damaged animals.

Alzheimer Disease↗
PubMed1986

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.

Alzheimer Disease↗
PubMed1986

Inputs to motoneurones in the hypoglossal nucleus of the rat: light and electron microscopic immunocytochemistry for choline acetyltransferase, substance P and enkephalins using monoclonal antibodies.

Light and electron microscopic peroxidase-antiperoxidase immunocytochemistry has been used to localize choline acetyltransferase, substance P and enkephalin in the hypoglossal nucleus of the rat. Choline acetyltransferase immunoreactivity was observed in motoneurone cell bodies and proximal dendrites, in large varicosities in the surrounding neuropil and in nerve terminals in synaptic contact with immunostained motoneurones. Most choline acetyltransferase immunostained terminals which made synaptic contact with motoneurone cell bodies and proximal dendrites possessed prominent subsynaptic cisterns and belong to the terminal type referred to in the literature as C or L. Substance P and enkephalin immunoreactivity did not occur in motoneurones but was seen in fibres and synaptic terminals. Substance P immunoreactive fibres made multiple axosomatic contacts while enkephalin immunoreactive terminals made synaptic contact mainly with large and small dendrites. C terminals were not stained for either substance P or enkephalin. This study provides immunocytochemical support for the classic identification of hypoglossal motoneurones as cholinergic and in addition shows that these neurones are innervated by a number of morphologically and chemically distinct terminal types. C terminals have previously been shown to contain cholinesterase and our demonstration that these terminals contain choline acetyltransferase thus provides additional evidence for their cholinergic nature and for a cholinergic innervation of hypoglossal motoneurones. The origin of the immunoreactive terminals was not identified in this study but possible candidates include the raphe nuclei for substance P. and propriobulbar interneurones for choline acetyltransferase.

Animals↗
PubMed1985

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.

Animals↗
PubMed1985

Hypertrophy of cholinergic neurones of the rat basal nucleus following section of the corpus callosum.

The effect of division of the corpus callosum on immunohistochemically identified cholinergic neurones of the basal nucleus has been examined in rats. Following callosal section the cholinergic cell bodies on both sides are significantly larger (25%) than those in normal animals. This hypertrophy persists for at least 62 days after operation, the longest survival time examined. It is greatest when the animal is operated on in infancy, but it occurs at all ages examined. The enlargement is similar to that seen in the cells of the same nucleus on one side following contralateral cortical damage.

Animals↗
PubMed1985

Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry.

The distribution of cholinergic neurons in the midbrain and pons which project directly to the thalamus was investigated in the rat using a procedure which allows the simultaneous detection of retrogradely transported horseradish peroxidase (HRP) and immunohistochemical demonstration of choline acetyltransferase (ChAT) in the same neurons. HRP injections were placed in the dorsal half of the anterior third of the thalamus on one side which included the anteroventral nucleus as well as portions of the rostral intralaminar and reticular nuclei. These thalamic nuclei showed the highest density of immunohistochemically detectable cholinergic fibers. Neurons containing both HRP and ChAT, which represented cholinergic neurons projecting directly to the thalamus, were found in the midbrain and pons in the lateral tegmental reticular formation, parabrachial region and lateral dorsal tegmental nucleus. Ipsilateral to the injection site over 91% of the HRP labeled neurons in all of these regions were cholinergic, while an average of 60% of the cholinergic neurons had transported HRP. Contralateral to the injection site 5-6% of the cholinergic neurons in these regions were also retrogradely labeled. These findings demonstrate direct cholinergic projections to the thalamus from neurons in several regions in the tegmentum and suggest that tegmental projections to the thalamus are predominantly cholinergic.

Animals↗
PubMed1985

Vasopressin- and neurophysin-immunoreactive neurons in the septal region, medial amygdala and locus coeruleus in colchicine-treated rats.

The distribution and morphology of neurons containing vasopressin, oxytocin and their associated neurophysins were examined immunohistochemically in rats given intracerebroventricular injections of colchicine. Under these conditions, numerous neurons containing vasopressin and neurophysin were found in several brain areas in addition to those previously described in the hypothalamus. Individual parvocellular vasopressin neurons were scattered in the medial and lateral septum and vertical limb of the nucleus of the diagonal band, while a large number of such neurons were found throughout both the bed nucleus of the stria terminals and the dorsal portion of the medial amygdala. In addition a small cluster of parvocellular vasopressin neurons was present adjacent to the top of the third ventricle in the posterior dorsal hypothalamic area and a number of such neurons were found in the ventral locus coeruleus and sub coeruleus. The mean diameters of these parvocellular vasopressin neurons ranged from 16.6 to 19.8 micron in the different regions, in contrast to the 25.4 micron mean diameter of hypothalamic magnocellular vasopressin neurons, or the 13.7 micron mean diameter of parvocellular vasopressin neurons in the suprachiasmatic nucleus. No vasopressin neurons were found in other brain and spinal cord regions under the conditions used in this study, although all regions were examined. No oxytocin neurons other than those previously described in the hypothalamus and immediately contiguous regions were found. Measurement of the mean diameter of oxytocin neurons showed that neurons in the caudal paraventricular nucleus were clearly smaller (18.9 micron) than magnocellular oxytocin neurons (24.8 micron) in other parts of the hypothalamus. These parvocellular oxytocin neurons with experimentally documented central connections were similar in both size and appearance to the parvocellular vasopressin neurons seen after colchicine treatment, which are potential sources of certain central vasopressin pathways. These findings indicate that there are at least two types of oxytocin neurons in the hypothalamus and several types of vasopressin neurons in a variety of different areas in the brain, many of which are outside of the hypothalamus.

Amygdala↗
PubMed1985

Effect of unilateral decortication on choline acetyltransferase activity in the nucleus basalis and other areas of the rat brain.

Acetyl-coenzyme A: choline O-acetyltransferase (EC 2.3.1.6) (ChAT) enzyme activity was measured in the nucleus basalis and other microscopically identified brain areas at various times after unilateral cortical lesions were made in the rat. Initially, a significant decrease in ChAT activity was detected in the nucleus basalis ipsilateral to the lesion. However, after 120 days ChAT activity had apparently recovered, as levels of the enzyme at that time were not significantly different from control values. No changes in ChAT activity could be detected in any of the other brain areas similarly studied. The significance of these findings and their relationship to the morphological changes seen in neurones of the nucleus basalis after cortical lesions are discussed.

Animals↗
PubMed1984

Hypertrophy of immunohistochemically identified cholinergic neurons of the basal nucleus of Meynert following ablation of the contralateral cortex in the rat.

The effects of unilateral damage of the cortex on cholinergic neurons identified by immunohistochemical demonstration of choline acetyltransferase, were examined in the basal nucleus of the rat. Those cells contralateral to the lesion showed significant hypertrophy as compared with cells in the same nucleus in age- and sex-matched control animals. This enlargement was present by 7 days and persisted after 300 days postoperatively, the longest survival time examined. The age of the animal at operation and the extent of the damage may influence the magnitude of the enlargement. Similar changes were seen in the cholinergic cells of the medial septal nucleus after removal of the contralateral hippocampus.

Acetylcholine↗
PubMed1984

Immunocytochemistry with monoclonal anti-immunoglobulin as a developing reagent: application to immunoperoxidase staining and radioimmunocytochemistry.

The development of two monoclonal antibodies for use as second antibodies in immunocytochemistry is described. The antibodies are produced by mouse X mouse hybrid myelomas, and are both of the IgG type. The two antibodies, RB23 and ND13, were used to detect neurophysin by three-step peroxidase-antiperoxidase (PAP) immunostaining, and were "internally labeled" with 3H-lysine for the radioimmunocytochemical localization of neurophysin, substance P, and tyrosine hydroxylase using rabbit first antibodies. The binding sites of RB23 and ND13 on the rabbit IgG antibodies were determined by solid-phase radioimmunoassay, using allotype-specific rabbit serum to compete with RB23 and ND13. It was found that both RB23 and ND13 are directed against the B4 kappa-light-chain allotype. The immunocytochemical localization of adrenocorticotropic hormone and somatostatin with rabbit primary antibodies was not achieved with RB23 or ND13, and it is proposed that these antibodies are not of the B4 allotype. The findings demonstrate that monoclonal second antibodies can be useful general reagents for conventional immunocytochemistry as well as for radioimmunocytochemistry. Furthermore, allotype-specific monoclonal second antibodies may prove useful in the simultaneous immunohistochemical localization of more than one antigen in a given tissue section.

Animals↗