L.M. Gonzalo

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.

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.

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.

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.

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.

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.