Reduction In Number Of Neurons Research Articles

The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics

Reductions of 40% in total cell number and 25% in volume of the mediodorsal thalamic nucleus were recently reported in an unbiased neurostereological study of neuroleptic-treated schizophrenic patients. In order to investigate whether these results might be secondary to many years of treatment with neuroleptic drugs, eight brains from schizophrenics never treated with neuroleptics and eight controls were studied using the unbiased Cavalieri volume estimator. To compare left-right differences in this region, twelve neuroleptic-treated schizophrenics and eleven control cases were compared. The brains used for the left-right comparison study and five of 20 used for comparison of treated and untreated brain volumes have been used in an earlier study. The mediodorsal thalamus volume was reduced by 31% in untreated schizophrenics and by 22% in neuroleptic-treated schizophrenics. No differences were found in mean total volume of the left and right mediodorsal thalamus in brains from controls nor from schizophrenics. A major difference exists with respect to time of fixation in controls (12 years) and untreated schizophrenics (39 years) that makes shrinkage differences a possible confounding variable. The results suggest that the consistent reduction in number of neurons in the mediodorsal thalamic nucleus are not secondary to prolonged treatment with neuroleptic drugs and that asymmetry in this specific brain region is not a feature of the schizophrenia-afflicted brain.

Quantitative changes during the postnatal maturation of the human visual cortex

Postnatal development of the human visual cortex is characterized by an overshooting growth pattern of its volume with a maximum at 8 postnatal months and by loss of a substantial proportion of its neurons. The highest rate of reduction in neuronal numbers is observed in layers II-IVa, with other layers showing a more gradual postnatal decrease.

The chronological relationship between the thickening of smooth muscle, epithelial cell proliferation and myenteric neural denervation in the rat jejunum

The jejunum of rats was treated by serosal application of a 0.2% solution of benzalkonium chloride (BAC) for 30 min. Control animals were treated with saline (0.9% NaC1). The animals were allocated to eight groups of 10 rats each and sacrificed 15, 30, 45, 60 days after BAC treatment. Segments were removed from the jejunum for neuronal counting, measurement of the smooth muscle area and morphokinetic study of the epithelium. There was a significant reduction in neuron number in the myenteric plexus 30 days after BAC treatment, thickening of smooth muscle 15-60 days after BAC treatment, but no change in epithelial cell proliferation in the jejunum at either time.

Effects of alternating monocular occlusion on the development of visual callosal connections

During normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. Visual experience early in life can modulate this process. In the present study, we investigated how restricting visual experience to alternating monocular occlusion affects the development of the callosal connections of cortical areas 17 and 18. Alternating monocular occlusion exaggerates the normally occurring partial elimination of immature callosal projection: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum and marginally increases the distribution of these neurons across areas 17 and 18. Examination of these data in the context of the effects of other types of abnormal early visual experience on the corpus callosum and on the anatomy and physiology of areas 17 and 18 indicates that the postnatal development of the corpus callosum is under the control of multiple, interacting influences which differ in the magnitude and quality of their effects. The data also support the conclusion, drawn from our results in prior studies, that normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections.

The neuroteratogenicity of procarbazine hydrochloride in the rat: Histopathological and immunocytochemical aspects

Procarbazine hydrochloride, an antineoplastic drug, was administered to pregnant rats from days 13 to 16 of gestation at doses of 0, 1, 5 and 15 mg per kg as part of a behavioural study. Histological examination of the brains from the offspring at 12 to 15 weeks of age revealed cerebral atrophy, which increased in severity with increasing dose, together with a reduction in neuronal numbers, with no apparent effect upon the astrocyte and oligodendrocyte populations.

Fall in the number of myenteric neurons in aging guinea pigs

The neurons of the myenteric plexus of the entire small intestine were stained in young adult (3–4 mo old) and aging guinea pigs (26–30 mo old). Total length and circumference of the intestine were measured in the same experiments. The small intestine of the aging guinea pigs was longer, and (in the conditions of distention used) had a total serosal surface ~70% greater than in young adult animals. The spatial density of myenteric neurons per unit of serosal surface fell dramatically in aging animals, and the total number of myenteric neurons in the small intestine ranged between 1.1 and 1.6 million, i.e., it was only 40%–60% of the value obtained in young adult guinea pigs (2.75 million). The light microscope appearance of the neurons of the two groups of animals was markedly different and the suggestion is put forward that in aging guinea pigs the substantial reduction in neuron number is accompanied by structural changes and reorganization of the neurons that are left.

Effects of unilateral cochlea removal on anteroventral cochlear nucleus neurons in developing gerbils.

Afferent regulation of neurons in the cochlear nucleus as a function of age was investigated at the light microscope level. Unilateral cochlea removal was performed on Mongolian gerbils of three age groups: 1, 8, and 20 weeks postnatal. Animals survived for either 2 days or 2 weeks. An additional group of neonatally operated animals had a prolonged survival of 9 weeks. The number of neurons in anteroventral cochlear nucleus (AVCN) was counted, and cross-sectional area measurements of large spherical cells in AVCN were made. In animals 1 week old at the time of surgery, there was a 35% reduction in neuron number in AVCN after 2 days, a 58% reduction after 2 weeks, and a 59% reduction 9 weeks after inner ear destruction. However, in animals 20 weeks old at the time of surgery, there was no cell loss in AVCN either 2 days or 2 weeks after surgery. Animals in each age group showed a reduction in cross-sectional area of large spherical cells in AVCN after cochlea ablation. The gerbils that underwent cochlea removal at 8 and 20 weeks showed an average decrease of 14-18%. This effect was seen as early as 2 days after cochlea removal. Animals that underwent cochlea removal at 1 week exhibited the greatest change; a 25% decrease at 2 days progressed to 38% at 2 weeks following cochlea removal. No appreciable further changes were seen at 9 weeks after neonatal cochlea removal. The results indicate greater susceptibility of 1-week-old gerbil cochlear nucleus neurons to peripheral loss than found in older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between natural variations in motoneuron number and body size in Xenopus laevis: a test for size matching.

During normal development, tadpoles of Xenopus laevis demonstrate large variations in body size that are carried through metamorphosis. This variation in size exists at the stages when lumbar lateral motor column (L-LMC) motoneurons are produced and when neuronal cell death in this neuron population occurs. Body size, hindlimb size, motoneuron number, and motoneuron size (i.e., neuron nuclear cross-sectional area) were measured in animals from three developmental stages: one prior to significant amounts of cell death, one at the peak rate of cell death, and one after cell death. The hypothesis that neuron population size is matched to peripheral size was tested by using the natural size variation found at each of these stages. The ranges of values for the measurements at the three stages were large. Significant correlations between body size and motoneuron number, as well as between motoneuron number and muscle fiber number, were present after cell death. Since these correlations emerged as cell death reduced neuron numbers, size matching may have occurred and cell death may have adjusted the L-LMC motoneuron population's size to variation in body size. In addition to the correlations between body size and motoneuron number at the end of cell death, neuron numbers before and after cell death were significantly correlated among groups of siblings. The possibility that the number of neurons after cell death was also influenced by differences in the number of L-LMC progenitors is discussed.

Development of mouse spinal cord in tissue culture: IV. Effects of embryonic extracts on neuron formation and migration.

Possible influences upon patterns of neurogenesis expressed in vitro were examined quantitatively by the use of microfragment cultures of embryonic day 10 mouse neural tube. Crude extracts were prepared either from whole embryos (day 13 or 15 of gestation) or from embryonic brains (day 18 of gestation) and added to the culture medium for the first 10 days of culturing. Neuronal outgrowth zones surrounding individual microfragments were reduced in area (indicating restricted neuronal migration) and in number of neurons present (indicating restricted production of neurons) following treatment with either of the extracts. The severity of reductions observed were related to the developmental age of embryonic tissue used for preparing the extract, as greatest reduction resulted from addition of embryonic day 18 brain extracts and to concentration employed, higher doses further restricting neuronal outgrowth. By increasing the concentrations of extract the proportional number of large-sized neurons forming the outgrowth zones became greater relative to the small neuron contribution, indicating an enhanced survival for this neuronal population. The formation and migration of astroglial precursor cells was not affected by the addition of any of the extracts. The number of neurons remaining within the original portions of neural tube microfragments was not significantly altered following culturing in the presence of embryonic extract. This suggested that the reduction in neuron number in the outgrowth zone actually reflected a decreased neuron production and was not simply the result of a retention of neurons within the remaining portion of the microfragment. The results suggest the presence of substances within mouse embryos that have regulatory effects on aspects of development of the central nervous system. Indications are that survival and maturation of postmitotic neuroblasts are promoted in vitro while the formation of additional neuronal progenitor cells may be partially inhibited by the addition of embryonic mouse extracts to the medium. We propose that an endogenous negative feedback mechanism may be involved in the coordination of patterns of neurogenesis.

The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in rat dorsal root ganglia

Nerve growth factor (NGF) is known to be essential for survival and maintenance of sympathetic ganglia and of embryonic sensory ganglia of neural crest origin. The present study examined the physiological and pharmacological roles of NGF in the postnatal development of sensory neurons in the dorsal root ganglion (DRG). In contrast to what is generally stated in the literature, administration of NGF antiserum to newborn rats for a period of 7 days resulted in a significant (approximately 20%) reduction of neuronal number in the lumbar DRG. Size spectrum analysis of surviving neurons revealed a shift toward larger sizes, presumably due to a preferential loss of small cells. The number of neurons in the L5 DRG was studied at various times after unilateral sciatic nerve crush in 1-day-old rats. Axotomy resulted in a substantial loss (40 to 50%) of neurons in the immature DRG. Administration of NGF antiserum to animals with axotomized DRG did not increase cell death when compared with the axotomized controls. However, the number of neurons in the antiserum-treated ganglia decreased by the same percentage (20%) when compared with the control serum-treated ganglia before and after axotomy. Treatment with NGF initially prevented the loss of neurons in the axotomized DRG. However, some neurons died during the first week despite continued NGF administration; and, subsequent to NGF withdrawal, neuronal number decreased to the same level as in control animals. Thus, removal of exogenous NGF resulted in the death of the sensory neurons which had been maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal development of the inferior olivary complex in the rat. III. A morphometric analysis of volumetric growth and neuronal cell number

The overall volume of the three main inferior olivary (ION) subnuclei increases four-fold between the day of birth (P0) and P21. The rate of this increase is uneven; between P10 and P15 there is an abrupt acceleration which parallels the period of intense synaptogenesis and maturation of the neuropil. The growth of the various subnuclei occurs in an almost synchronous manner. A study discloses that the postnatal volumetric increase is the result of the development of the neuropil and the glial cells. The numerical estimation of neuronal perikarya was made for each ION subnucleus from P0 to P33. However, due to methodological problems, the quantitation becomes reliable only from P5 onwards. From P5 to P8, there is a small (10%) but consistent decrease in the number of olivary neurons, a decrease which is homogeneously shared by the 3 main subnuclei. This phase of reduction in neuronal numbers, indicative of cellular death, is followed by an increase of similar magnitude, between P10 and P15. Since the phase of apparent olivary cell death coincides with the peak of the regression of the multiple innervation of Purkinje cells (PCs) by climbing fibers (CFs), both processes might be interrelated. However, the slight amplitude of the cell death is inadequate to fully explain the whole process of synaptic regression. These results indicate a dual nature of the mechanism underlying the establishment of the one-to-one relationship between CFs and PCs: a small proportion of the regression results from cell death, while the largest proportion must be the result of a loss of collaterals from the olivary axons at the origin of the CFs. The problem of the increase in the number of ION neurons between P10 and P15 is discussed in relation to recent morphometric data indicating a late increase in the number of PCs of the cerebellum.

Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading.

The various structural components of the cortical degeneration of Alzheimer's disease were defined and graded. The severity of the degenerative process was thus mapped in different cortical areas where neuronal numbers and cortical width were also measured and compared with controls. Contrary to the general opinion that the degenerative process is rather uniformly diffuse, though accentuated in the medial temporal and frontal cortex, we found a consistent and more elaborate pattern with clearcut regional differences. Thus the degeneration involved, besides basal medial temporal limbic areas, the posterior cingulate gyrus and superior parietal lobule particularly, with somewhat less marked changes in the inferior parietal lobule and inferior temporal gyri. The sensorimotor, calcarine and anterior cingulate areas of the cortex were notably spared until very late stages. This regionally variable severity of the degeneration was also paralleled by a regionally varying reduction in neuronal numbers and cortical width, and agrees with our previously published results of a regional pattern which closely correlates with clinical parameters, including symptom pattern and regional cerebral blood flow alterations.

Transported enzymes in sciatic nerve and sensory ganglia of rats exposed to maternal antibodies against nerve growth factor.

The accumulations by axoplasmic transport of selected enzyme activities proximal and distal to a ligature placed on the sciatic nerve were monitored in rats exposed in utero to maternal antibodies to nerve growth factor (NGF) and in control rats. Littermates of the animals exposed to anti-NGF were shown elsewhere to have had a 70% reduction in the number of sensory neurons in dorsal root ganglia and a 90% reduction in number of neurons in superior cervical (sympathetic) ganglion. The accumulation of F(-)-sensitive acid phosphatase activity was depressed 75% both proximal and distal to the tie. Accumulation of F(-)-resistant acid phosphatase activity was depressed nearly 50% proximal to the tie. Distal accumulation of this activity did not occur in either group of rats. Accumulation of acetylcholinesterase activity was depressed 30%. Distal accumulation of the activities of beta-glucuronidase and hexokinase was depressed 50%. In the lumbar dorsal root ganglia, dry weight was reduced 40%, and the activities of peroxide-sensitive, F(-)-resistant acid phosphatase and of the mitochondrial enzymes hexokinase, glutamic dehydrogenase, glutamic-oxalacetic transaminase, and NAD-dependent isocitric dehydrogenase were all reduced a little more, 45--50% per ganglion. However, the activities of the lysosomal enzymes, F(-)-sensitive acid phosphatase and beta-glucuronidase, of the peroxide-resistant, F(-)-resistant acid phosphatase, and of the mitochondrial enzyme glutaminase were all reduced about 60% per ganglion. The results of these measurements were interpreted to suggest that much, and perhaps all, of the F(-)-sensitive acid phosphatase activity in motion in peripheral nerve in rat is confined to sensory axons.

A histoquantitative study of the striate cortex and lateral geniculate body in normal, blind and demented subjects.

The amount of myelin in the outer band of Baillarger in the human visual cortex stained by Luxol Fast Blue MBS, has been measured in normal individuals of wide age range, in a group of blind and severely visually impaired but otherwise normal individuals and in a series of demented patients of the Alzheimer and multi-infarct type who were apparently visually normal. The amount of myelin is found to be significantly reduced in the blind and demented groups. Examination of the lateral geniculate body in the blind cases demonstrated slight reduction in neuron numbers and marked reduction in mean neuron diameter. Neuronal cytoplasmic ribonucleic acid, nucleolar volume and numbers of tetraploid glial nuclei in the blind or visually impaired cases were significantly reduced when compared with controls, indicating reduced function in these neurons. Similar results were obtained on examining this nucleus in Alzheimer and multi-infarct cases, suggesting that the visual pathways may be involved in these conditions. It is concluded that loss of myelin from the outer band of Baillarger occurs in association with reduced function of neurons in the lateral geniculate body.

Effects of long-term nerve growth factor deprivation on the nervous system of the adult rat: An experimental autoimmune approach

Adult rats immunized with 2.5S mouse nerve growth factor (NGF) produced antibodies which cross-reacted with rat NGF. By the criterion of ammonium sulfate precipitation followed by Sephadex G-200 chromatography, all serum anti-NGF activity was retained in the IgG fraction. Animals which developed and maintained chronic (5–6 months) serum titers of anti-NGF demonstrated a pronounced biochemical and morphological atrophy of the superior cervical ganglion which was accompanied by a 35–40% reduction in neuronal number. Norepinephrine was reduced by approximately 90% in heart and brown fat. The extent of biochemical atrophy correlated well with serum titers of anti-NGF. No effects were observed on the short adrenergic neurons of the vas deferens, adrenal medullary chromaffin cells, central adrenergic neurons, or peripheral sensory neurons. These results strongly suggest that mature peripheral sympathetic neurons remain dependent on NGF for survival as well as for maintenance.