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L M Gonzalo

Publications and source records attributed to L M Gonzalo.

At least 19 recordsLinked to original sources

Neuropathological changes in the nucleus basalis correlate with clinical measures of dementia.

The present study correlates the severity of dementia in Alzheimer's disease with the degree of neuropathology present in the nucleus basalis of Meynert. We assessed neurofibrillary tangles, neuronal loss and morphometric changes in 21 patients with Alzheimer's disease who underwent extensive neuropsychological testing before death. We report a highly significant correlation between scores in the psychological tests and all of the neuropathological markers examined within the nucleus basalis of Meynert. The test that correlated most closely with these morphological measures was Folstein's Mini Mental State. Among the different neuropathological changes, the number of neurofibrillary tangles was strongly correlated with the degree of dementia. We also provide evidence for a differential involvement of the three subdivisions of the nucleus basalis in Alzheimer's disease neuropathology. The posterior subdivision, which provides a substantial cholinergic input to the parahippocampal gyrus, was the more profoundly affected. Taken together, these results point to an important participation of the nucleus basalis in dementia of the Alzheimer type. In addition, the strong correlation between neuropathological changes and neuropsychological scores indicates the reliability of these tests in assessing the progression of the disease.

Aged↗

Diet induced hyperammonemia decreases neuronal nuclear size in rat entorhinal cortex.

Hepatic encephalopathy is mainly caused by an excess of ammonium ions. Among other effects, glutamate transmission in the brain is impaired, and thereof, neuronal function in multiple systems is affected. We investigated in rats the effect of diet induced hyperammonemia in the entorhinal cortex, a well known glutamatergic pathway to the dentate gyrus, by measuring the neuronal nuclear area in two entorhinal cortex subfields (dorsolateral subfield (DLE) and dorsal intermediate subfield (DIE); [Insausti, R., Herrero, M.T. and Witter, M.P., Origin and distribution of cortical efferents from the entorhinal cortex in the rat, Hippocampus, 7 (1997) 146-183]) that project to separate septotemporal levels of the hippocampus. After 2, and more overtly, after 8 weeks of the ammonium enriched diet consumption, the neuronal nuclear size in layers II, III, V and VI of both entorhinal cortex subfields showed a significant reduction in size. We conclude that already at 2 weeks of treatment there is a decrease in neuronal nuclear size in all layers of the entorhinal cortex, which might have widespread functional effects on cortical and subcortical structures.

Acetates↗

The human entorhinal cortex: a cytoarchitectonic analysis.

The entorhinal cortex of man is in the medial aspect of the temporal lobe. As in other mammalian species, it constitutes an essential component of the hippocampal formation and the route through which the neocortex interacts with the hippocampus. The importance of knowing its architecture in detail arises from the possibility of extrapolating it to experimental findings, notably in the nonhuman primate. We have investigated the cytoarchitectonic features of the human entorhinal cortex by using as a base our previous study (D.G. Amaral, R. Insausti, and W.M. Cowan [1987] J. Comp. Neurol. 264:326-355) of the nonhuman primate entorhinal cortex. We prepared serial sections of the temporal lobe from 35 normal brains. Thionin- and myelin-stained series were made of all cases. Sections spaced 500 microns apart through the full rostrocaudal extent of the entorhinal cortex were analyzed. The human entorhinal cortex is made up of six layers, of which layer IV does not appear throughout all subfields of the entorhinal cortex. The overall appearance resembles that of the adjacent neocortex in lateral and caudal portions. In harmony with general structural principles in the nonhuman primate entorhinal cortex, our analysis supports the partitioning of the human entorhinal cortex into eight different subfields. (1) The olfactory subfield (EO), the rostralmost field, is little laminated. (2) The lateral rostral subfield (ELr), laterally located, merges with the laterally adjacent perirhinal cortex. (3) The rostral subfield (ER) is between EO and ELr, with better differentiation of layers II and III than EO. (4) The medial intermediate subfield (EMI) is located at the medial border. (5) The intermediate field (EI) is a lateral continuation of EMI; lamina dissecans (layer IV) can be best appreciated in this field. (6) The lateral caudal subfield (ELc) laterally borders on EI as a continuation of ELr. (7) The caudal subfield (EC) lies caudal to the beginning of the hippocampal fissure, with a distinctive, clear space (Vc) between layers V and VI. (8) The caudal limiting field (ECL) forms the caudal termination of the entorhinal cortex. Thus our parcellation of the entorhinal cortex in man is largely parallel to that arrived at in the monkey. This close homology provides a rational basis for the application to clinical problems of anatomical and functional information obtained in experimental work in nonhuman primates.

Adolescent↗

Chronic alcoholism decreases neuronal nuclear size in the human entorhinal cortex.

The effect of chronic alcoholism in the neuronal nuclear area (karyometry) of the lateral entorhinal cortex at three rostro-caudal levels (rostral, intermediate and caudal) has been studied in 19 alcoholic subjects and in 15 aged-matched controls. Cases were distributed into three groups according to their age (29-44, 45-60 and 61-70 years of age). In the second group (45-60 years), the nuclear size in layers II and III of the caudal entorhinal cortex showed a very significant decrease compared to controls. The first group (29-44 years) also showed a significant reduction in size, while the third group presented the smallest differences. The presence of cirrhosis in the alcoholic group did not vary the observed results. Thus, chronic alcoholism significantly decreases the nuclear size in layers II and III of the lateral entorhinal cortex, and thus the entorhinal output to the hippocampus may be altered in alcoholism.

Adult↗

Effect of chronic alcoholism on neuronal nuclear size and neuronal population in the mammillary body and the anterior thalamic complex of man.

The effect of chronic alcoholism on neuronal nuclear size and neuronal population of two memory-related diencephalic centres, the mammillary body and the anterior thalamic complex, has been examined in 24 chronic male alcoholics and 22 age-matched male controls. Cases were subdivided into three age groups (30-44 years, 45-59 years and 60-75 years). The results showed a significant reduction in both neuronal numbers and nuclear size in alcoholics compared to controls. Differences were especially high in the youngest alcoholics. The intensity of liver damage (steatosis vs. cirrhosis) did not have any significant effect. Moreover, an age-related decrease of neuronal number and karyometry was seen in controls but not in alcoholics. Our results suggest that chronic alcoholism accelerates the rate of neuronal loss in the mammillary body and anterior thalamic complex to a degree equivalent to aging. Likewise, chronic alcoholism impairs the compensatory increase in neuronal nuclei area seen in normal aging in these same structures. Our findings show that medial diencephalic memory centres are damaged in chronic alcoholism, which may contribute to the clinical symptomatology of these persons.

Adult↗

Cell loss in supraoptic and paraventricular nucleus in Alzheimer's disease.

Previous studies have shown an activation of the hypothalamo-neurohypophyseal system (HNS) in normal aging and in senile dementia. Among other explanations, this activation might be secondary to cell loss in the supraoptic (SO) and paraventricular (PV) nuclei. This study reports a 63% loss in the SO and a 56% loss in the PV in a group of Alzheimer disease (AD) patients. The remaining neurons undergo a compensatory hypertrophy that is more pronounced in the SO, affecting cell and nuclear size as well as nucleolar volume. The group of patients with a diagnosis of moderate dementia showed the greatest hypertrophy, as compared to the severely demented patients. Our results suggest that there is a compensatory capacity in the earlier stages of the dementia, that is lost in the final stages of Alzheimer's disease.

Aged↗

Urinary bladder innervation in male rat: termination of primary afferents in the spinal cord as determined by transganglionic transport of WGA-HRP.

The distribution of afferents innervating the urinary bladder in the spinal cord of male rats has been studied with the axonal tracer horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) injected into various portions of one side of the urinary bladder (dome, body, base, or neck) and other pelvic organs (prostate and rectum). Labeled neurons were found in dorsal root ganglia of the lumbosacral cord (L1-S3, peak in S1-S2). The strongest and most extensive transganglionic labeling of primary afferents resulted after injections in the body of the bladder. Primary afferents were observed bilaterally in Lissauer's tract and laminae I-II at the apex of the dorsal horn, from L6 to S3. The projection extended laterally up to the sacral parasympathetic nucleus and medially up to the gray matter dorsal to the central canal, where they formed a plexus of fibers and terminals. Deposits in the dome and base of the bladder labeled more heavily the medial projection, while the least intense projection was seen after injections in the bladder neck. Our results indicate a common pattern of termination of primary afferents from the bladder, although some topographical differences exist.

Afferent Pathways↗

Neuromelanin accumulation with age in catecholaminergic neurons from Macaca fascicularis brainstem.

Neuromelanin (NM) is an auto-oxidation by-product of catecholamine synthesis which is observed almost exclusively in primates. We have estimated the distribution and the number of NM-positive neurons of the upper brainstem and the degree of their melanization from birth to the onset of senescence in 5 monkeys (Macaca fascicularis) aged 0, 1.5, 3.5, 8 and 13 years. Series of sections taken at 640-microns intervals were examined either unstained to detect unstained NM, stained for NM with Masson silver impregnation or processed by tyrosine hydroxylase (TH) immunohistochemistry to analyze catecholaminergic neurons. The proportion of NM-containing cells among TH-positive neurons varied from one catecholaminergic region to another: low in the hypothalamus and central gray substance (cgs); moderate in the cell group A8, and high in the ventral tegmental area (VTA), locus coeruleus (LC) and substantia nigra (SN). TH-positive neurons were detected in the SN, VTA, catecholaminergic cell group A8, LC, cgs and hypothalamus. At birth, although no unstained NM-positive neurons were detected, Masson-stained cells were observed, though only in the LC. At 1.5 and 3.5 years, Masson-positive neurons were observed despite the absence of visible pigment. At 8 and 13 years, unstained NM was present in Masson-positive neurons. The number of unstained NM-positive neurons and Masson-positive neurons and the amount of NM per neuron increased with age in each subregion studied. Nevertheless, some TH-positive neurons were found to be without NM. The data indicate a differential increased NM content with age in the neurons of midbrain catecholaminergic cell groups. However, its functional significance remains to be determined.

Aging↗

Short-term ethanol intoxication in rat. Effect on the entorhinal cortex.

The effect of short-term ethanol intoxication in systems implicated in memory and other cognitive functions in rats has been assessed by studying the variation in the karyometry of the neurons in the different layers of the lateral entorhinal cortex. The analysis showed that short-term ethanol consumption produced a reduction in the nuclear area of neurons in layers V and VI, and to a lesser extent, in layers II and III. These results suggest that the deep layers of the entorhinal cortex are more sensitive to ethanol intoxication, thus more likely affecting cortical and subcortical projections than the hippocampal output.

Acute Disease↗

Pudendal nerve topography in the rat spinal cord projections studied with the axonal tracer wheat germ agglutinin conjugated-horseradish peroxidase.

The spinal cord termination of the sensory fibers of the rat pudendal nerve has been determined by using the transganglionic transport of horseradish peroxidase conjugated to wheat germ agglutinin. The gross anatomical examination of the pudendal plexus indicated the existence of dorsal and ventral branches in the sensory division of the pudendal nerve. Either branch or both were sectioned and exposed to a 1% solution of the enzyme. After an average survival period of 48 hours, the resulting reaction product was studied both at the level of the dorsal root ganglia and the spinal cord. Labeled dorsal root ganglion cells were observed between L1 and S4 (peak in S1 and L6). Evidence of transganglionic transport of the tracer was observed from L5 to S2. The ventral branch projected medially in the superficial dorsal horn, while the dorsal branch projected laterally. Our findings are consistent with a segregation of sensibilities for the ventral and dorsal branches that convey urogenital (ventral branch) and anal (dorsal branch) cutaneous sensations at the level of termination of primary afferents.

Anal Canal↗

Ageing of the human entorhinal cortex and subicular complex.

Age-dependent changes in the entorhinal cortex (EC) and subicular complex (SC) were studied in 30 brains of patients who died between 14 and 86 years of age, without CNS impairment, as determined by macro- and microscopic examination. The brains were fixed in 10% formalin and embedded in paraffin. Three series of coronal EC and SC sections (7 microns) were stained by Nissl, PAS or hematoxylin-eosin. Using neuronal count and Kariometry, age-dependent modifications were studied in layers II, III and V of the lateral area of the EC; in the pyramidal layer of the subiculum (S), and in layer II of the presubiculum (PS). All EC layers studied presented a slight (11-20%) although significant reduction up to 35 years, but from 35 to 75 years the decrease was not significant. After 75 years the neuronal loss increased slightly. The nuclear area decreased up to the age of 40-45 years, (10-18%) and augmented from this age up to 75 years (10-14%). During the last period of life, the nuclear area did not change. From 30-60 years, pyramidal layer in the S showed a significant neuronal loss (30%), thereafter, neuronal reduction was less. At early years, the nuclear area decreased insignificantly (15%), and from 35 years up to the most advanced age studied, it increased significantly (13%). In the PS, layer II manifested a cell loss throughout the lifespan (32.9%) and the changes in the nuclear area did not reach statistical significance due to the dispersions of its values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cortically projecting cells in the periaqueductal gray matter of the rat. A retrograde fluorescent tracer study.

The topographical organization of the afferent input from the periaqueductal gray matter (PAG) to the cerebral cortex has been assessed in rats by retrograde transport of the fluorescent tracers Fast blue (FB) and Diamidino yellow (DY). The olfactory, medial frontal (infralimbic, prelimbic and anterior cingulate cortices), lateral frontal (motor), parietal, temporal, occipital and insular cortices were explored by placing two fluorescent tracers into two different cortical regions. The PAG contained the largest number of labeled neurons in medial frontal cortex injections, followed by olfactory and lateral frontal cortices. Fewer retrogradely labeled cells were seen after injections in parietal, temporal occipital and insular cortices. All labeled cells were exclusively located in the medial and lateroventral divisions of the PAG (PAGm and PAGlv). The longitudinal extent of the labeling in PAGm was more extensive than in PAGlv. The labeled neurons in the medial frontal cortex group extended through most of the PAG, while in the remaining groups it was restricted to the caudal one-third of the PAG. Neurons with projections to two different cortical regions were only a small fraction of the total population of labeled cells. Our data indicate that the medial frontal cortex is the most important recipient of a direct PAG input, followed by the lateral frontal cortex. Parietal, temporal, occipital and insular cortices receive only a minor projection. It is concluded that the PAG sends direct projections over the majority of the cortical mantle. Therefore, the possibility arises that the cerebral cortex receives a direct influence from the brainstem without a thalamic relay.

Animals↗

Cortical projections from the laterodorsal and dorsal tegmental nuclei. A fluorescent retrograde tracing study in the rat.

Cortical injections of the fluorescent tracers Fast blue and Diamidino yellow resulted in retrogradely labeled cells in the dorsal tegmental region of the rat. Both the laterodorsal tegmental nucleus and the ventromedial portion of the dorsal tegmental nucleus presented labeled cells. Topographically, the most robust projection was directed to the medial frontal cortex, followed by the olfactory and lateral frontal (motor) cortex. Fewer labeled cells appeared after parietal, temporal or occipital cortex injections.

Amidines↗

Effects of alcoholization on the rat hippocampus.

The effects of ethanol intoxication on the hippocampus (H) has been studied in 18 (5 died) Sprague-Dawley rats (group A), 5 other rats served as control (group C). The weight of the animals at the beginning of experiment was 135-140 g and, at the end, 234 g for group A and 240 g for group C. Both groups were given a liquid diet. In group A, the ethanol provided 36% of the total calories; in group C these calories were supplied as dextrin-maltose. The average of the diet alcoholemia was 159.6 mg/100 ml. After 70 days of alcohol intake, the rats were transcardially perfused, and brain and liver were removed. The liver of the alcoholic rats exhibited an intense steatosis, and the H showed important modifications in number of neurons as well as in nuclear size. The neuron loss in group A, with respect to group C was: highly significant (P less than 0.001) for CA2; very significant (P less than 0.01) for CA3 and CA4; in CA1 and GD the reduction was not significant. In spite of neuron loss, the nuclear area showed a reduction in size: highly significant in CA2 and CA4; very significant in GD, but in CA2 and CA3 the reduction did not reach statistical significance. These results confirm the lethal influence of ethanol on some neurons, and the limited ability of the remnant neurons to compensate for neuronal loss.

Alcoholism↗

Cell loss and nuclear hypertrophy in topographical subdivisions of the nucleus basalis of Meynert in Alzheimer's disease.

The nucleus basalis of Meynert was examined in six patients with Alzheimer's disease and five age-matched controls. A cytoarchitectonic study was followed by quantitative analysis of the population of neurons and by the determination of their nuclear area. Confirming previous neuropathological observations in Alzheimer's disease, a neuronal loss of 43% in the anterior, 25% in the intermediate and 30.5% in the posterior subdivisions of the nucleus basalis of Meynert was observed. Numerous surviving cells showed neurofibrillary tangles. In addition, we found that the nuclear area of the remaining nucleus basalis of Meynert neurons was significantly increased in all three subdivisions by at least 16%. The combined observation of cell loss and nuclear hypertrophy suggests that both regenerative and degenerative changes co-exist in the nucleus basalis in Alzheimer's disease.

Aged↗

Ascending projections to the first two myelomeres.

Afferent fibres to the first 2 myelomeres arising from more caudal spinal segments have been studied in rats by means of retrograde transport of wheat germ agglutinin-horse radish peroxidase (WGA-HRP). In 10 Wistar rats 30 nl of a 1% WGA-HRP solution were injected into the right dorsal horn of the first or second cervical segments. The results were similar for both levels. Labelled neurons were observed in all spinal myelomeres but their density was higher in cervical than in thoracic regions. The laminar distribution was, in decreasing order: V, VII, VIII, IV and X, and the location of labelled neurons in these laminae was predominantly medial. Both sides of the spinal cord contained labelled neurons, but these were more numerous on the ipsilateral side. The dorsal laminae did not show labelled neurons. The number of labelled cells was larger when the WGA-HRP deposit reached laminae V, VI and VII. These results suggest that nerve impulses arising in more caudal dermatomes may modulate the excitability of centrally transmitting neurons in the first 2 cervical myelomeres.

Afferent Pathways↗

Effect of chronic alcoholism on the human hippocampus.

The effect of chronic alcoholism on the human hippocampus was studied in 21 patients, divided in 4 groups: Group A under 45 years, group B 46-59 years, group C 60-69, and Group D over 70 years; and compared with age-matched control patients who died without neurological complications. The gyrus dentatus and the ammonic fields CA1 through CA4 were analyzed by counting the number of neurons and the size of the nuclear area. Both parameters were evaluated statistically. The most important findings were a high neuronal loss in alcoholics in the first age group. In addition, the hippocampal neurons failed to display a vicarious reaction, since the nuclei did not show any increase in size despite the intense neuronal loss. Our results point out an early neuronal loss in the hippocampus of alcoholic patients higher than age-matched controls, as well as a lack of reaction to the neuronal insult.

Adult↗

The pelvic innervation in the rat: different spinal origin and projections in Sprague-Dawley and Wistar rats.

WGA-HRP was applied to the pelvic and pudendal nerves of Sprague-Dawley and Wistar rats to compare the segmental levels of the resulting labeling. L6 and S1 were the segments at which the sacral parasympathetic nucleus and the denser primary afferents occurred in Sprague-Dawley rats. The levels found in Wistar rats were S1 and S2, thus indicating a disparity between both strains of rats in the spinal level of the sacral parasympathetic nucleus and the primary afferents.

Afferent Pathways↗