3-Acetylpyridine-induced ataxic-like motor impairments are associated with plastic changes in the Purkinje cells of the rat cerebellum.

Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.

Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas / Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex

INTRODUCCIÓN: Diversas enfermedades neuropatologías asociadas a la degeneración del tracto corticoespinal muestran deterioro de las funciones motoras. Tales alteraciones neurológicas se asocian a diversos fenómenos plásticos subsecuentes, a nivel tanto presináptico como postsináptico. Sin embargo, no existe evidencia que indique la existencia de modificaciones en la transmisión de información del tracto corticoespinal a las motoneuronas espinales. MÉTODOS: Se indujo una lesión por vía estereotáxica en la corteza motora primaria de ratas hembra adultas con ácido kaínico y, 15 días después, se evaluó el desempeño motor mediante la escala BBB y en un dispositivo Rota-Rod. Paralelamente, se cuantificó la densidad numérica y proporcional de las espinas delgadas, en hongo y gordas, en motoneuronas de un segmento torácico-lumbar de la médula espinal. Así mismo, se registró la expresión de las proteínas espinofilina, sinaptofisina β III-tubulina. RESULTADOS: La lesión farmacológica provocó un desempeño motor deficiente. Así mismo, tanto la densidad de espinas como la proporción de espinas delgadas y gordas fue mayor, al igual que la expresión de las 3 proteínas estudiadas. CONCLUSIÓN: La aparición de los síntomas clínicos de daño neurológico provocado por la degeneración walleriana del tracto corticoespinal se acompaña de respuestas plásticas espontáneas de tipo compensador, a nivel sináptico. Lo anterior indica que durante la rehabilitación temprana de este tipo de pacientes, la plasticidad espontánea constituye un factor que se debe considerar para el diseño de estrategias de intervención más eficientes

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and β III-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex. / Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas.

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and ß iii-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation.

Plastic changes to dendritic spines in the cerebellar and prefrontal cortices underlie the decline in motor coordination and working memory during successful aging.

Old age is the last stage of life and by taking a multidimensional view of aging, Neuroscientists have been able to characterize pathological or successful aging. Psychomotor and cognitive performance are recognized as two major domains of successful aging, with a loss of motor coordination and working memory deficits two of the most characteristic features of elderly people. Dendritic spines in both the cerebellar and prefrontal cortices diminish in aging, yet the plastic changes in dendritic spines have not been related to behavioral performance neither the changes in the cerebellar or prefrontal cortices. As such, motor coordination and visuospatial working memory (vsWM) was evaluated here in aged, 22-month-old rats, calculating the density of spines and the proportion of the different types of spines. These animals performed erratically and slowly in a motor coordination-related paradigm, and the vsWM was resolved deficiently. Spine density was reduced in aged animals, and the proportional density of each of the spine types studied diminished in both the brain regions studied. The loss of dendritic spines and particularly, the changes in the proportional density of the different spine types could underlie, at least in part, the behavioral deficits observed during aging. To our knowledge, this is the first study of the plastic changes in different dendritic spine types that might underlie the behavioral alterations in motor and cognitive abilities associated with aging. Further neurochemical and molecular studies will help better understand the functional significance of the plastic changes to dendritic spines in both successful and pathological aging.

El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas / No disponible

INTRODUCCIÓN: El lóbulo paramediano del cerebelo está involucrado en el desempeño correcto de las habilidades motoras a través de la práctica. Las espinas dendríticas son estructuras dinámicas que regulan la estimulación sináptica excitadora. En este trabajo se estudiaron los posibles cambios plásticos en espinas de células de Purkinje del lóbulo paramediano cerebelar de ratas, durante el aprendizaje motor. MÉTODOS: Se entrenaron a ratas macho adultas durante un período de seis días, en un paradigma de aprendizaje motor acrobático y se cuantificó tanto la densidad como los tipos de espinas dendríticas en cada uno de los seis días de estudio, mediante una modificación al método de Golgi. RESULTADOS: La curva de aprendizaje reflejó una disminución consistente de los errores cometidos en el transcurso de los días de entrenamiento. Así mismo, se observaron más espinas dendríticas en los días 2 y 6 y, en particular, más espinas delgadas en los días 1, 3 y 6, menos espinas en hongo el día 3, menos espinas gordas el día 1 y más espinas anchas los días 4 y 6. CONCLUSIÓN: El período inicial de aprendizaje motor podría estar asociado con el procesamiento rápido de la información sináptica subyacente y con un aparente «silenciamiento» de los procesos de consolidación mnémica, en una base de regulación de la excitabilidad neuronal

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability

Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum. / El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas.

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability.

A Golgi study of the plasticity of dendritic spines in the hypothalamic ventromedial nucleus during the estrous cycle of female rats.

Estradiol-induced plasticity involves changes in dendritic spine density and in the relative proportions of the different dendritic spine types that influence neurons and neural circuits. Such events affect brain structures that control the timing of neuroendocrine and behavioral processes, influencing both reproductive and cognitive functions during the estrous cycle. Accordingly, to investigate the dendritic spine-related plastic changes that may affect the neural processes involved in mating, estradiol-mediated dendritic spine plasticity was studied in type II cells situated in the ventrolateral portion of the ventromedial hypothalamic nucleus (VMN) of female, adult rats. The rats were assigned to four different groups (n=6) in function of their stage in the estrous cycle: proestrus, estrus, metaestrus, and diestrus. Dendritic spine density and the proportions of the different spine types on type II neurons were analyzed in the ventrolateral region of the VMN of these animals. Dendritic spine density on primary dendrites of VMN type II neurons was significantly lower in metaestrus than in diestrus, proestrus and estrus (with no differences between these latter stages). However, a significant variation in the proportional density of the different spine types was found, with a higher proportion of thin spines in diestrus, proestrus and estrus than in metaestrus. Likewise, a higher proportion of mushroom spines was seen in diestrus and proestrus than in metaestrus, and a higher proportion of stubby spines in estrus than in diestrus and metaestrus. Very few branched spines were found during proestrus and they were not detected during estrus or metaestrus. The different types of dendritic spines in non-projection neurons of the VMN could serve to maintain greater synaptic excitatory activity when receptivity and estradiol levels are maximal. However, they may also fulfill an additional functional role when receptivity and estradiol decline. To date specific roles of the different types of spines in neural hypothalamic activity during the estrous cycle remain unknown and they clearly deserve further study.

Effects of selective estrogen receptor modulators on allocentric working memory performance and on dendritic spines in medial prefrontal cortex pyramidal neurons of ovariectomized rats.

Estradiol and some selective estrogen receptor modulators (SERMs) are neuroprotective in a variety of experimental models of neurodegeneration, reduce the inflammatory response of glial cells, reduce anxiety and depression, promote cognition and modulate synaptic plasticity in the hippocampus of rodents. In this study we have assessed whether estradiol and two SERMs currently used in clinics, tamoxifen and raloxifene, affect medial prefrontal cortex function and morphology. Rats were ovariectomized and six days later some animals received a subcutaneous injection of the estrogenic compounds. In a first experiment animals were treated with estradiol benzoate or sesame oil vehicle. In a second experiment animals received raloxifene, tamoxifen or dimethyl sulfoxide as vehicle. Twenty four hours after the pharmacological treatment, animals were challenged to solve an allocentric working memory paradigm in a "Y" maze. Twenty trials consisting of a study phase and a test phase were conducted according to a delayed match-to-sample procedure in a single one-day session. Animals that were not submitted to behavioral test were used for Golgi analysis of the prefrontal cortex. Rats treated with estradiol benzoate, tamoxifen or raloxifene performed better in the Y maze and showed a significant increase in the numerical density of dendritic spines in secondary apical dendrites of layer III pyramidal neurons from the prelimbic/infralimbic prefrontal cortex, compared to their respective control groups. These findings suggest that estradiol, tamoxifen and raloxifene improve prefrontal cortex-related cognitive performance and modulate prefrontal cortex morphology in ovariectomized rats.

Morphological development of dendritic spines on rat cerebellar Purkinje cells.

The posterior cerebellum is strongly involved in motor coordination and its maturation parallels the development of motor control. Climbing and mossy fibers from the spinal cord and inferior olivary complex, respectively, provide excitatory afferents to cerebellar Purkinje neurons. From post-natal day 19 climbing fibers form synapses with thorn-like spines located on the lower primary and secondary dendrites of Purkinje cells. By contrast, mossy fibers transmit synaptic information to Purkinje cells trans-synaptically through granule cells. This communication occurs via excitatory synapses between the parallel fibers of granule cells and spines on the upper dendritic branchlets of Purkinje neurons that are first evident at post-natal day 21. Dendritic spines influence the transmission of synaptic information through plastic changes in their distribution, density and geometric shape, which may be related to cerebellar maturation. Thus, spine density and shape was studied in the upper dendritic branchlets of rat Purkinje cells, at post-natal days 21, 30 and 90. At 90 days the number of thin, mushroom and thorn-like spines was greater than at 21 and 30 days, while the filopodia, stubby and wide spines diminished. Thin and mushroom spines are associated with increased synaptic strength, suggesting more efficient transmission of synaptic impulses than stubby or wide spines. Hence, the changes found suggest that the development of motor control may be closely linked to the distinct developmental patterns of dendritic spines on Purkinje cells, which has important implications for future studies of cerebellar dysfunctions.

Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicity.

Hippocampal vulnerability to excitotoxicity has been widely studied along with its implication to learning and memory. Neonatal glutamate excitotoxicity induces loss of CA1 pyramidal neurons in adult rats concomitantly with some plastic changes in the dendritic spines of surviving neurons. At least in part, these may underlie the place learning impairments seen in previous studies based on a similar excitotoxicity-inducing model. In the present study, cytoarchitecture of dentate gyrus, CA3 and CA1 fields were evaluated in 120-day-old rats, after they had been neonatally treated with glutamate as monosodium salt. Dentate granule cells and CA1 pyramidal neurons were less than those counted in NaCl-treated control animals. In addition, dentate granule cells had more dendrites as well as more branched spines. Spine density in CA1 pyramidal neurons was greater than in the controls. Additionally, thin and mushroom spines were proportionally more abundant in monosodium glutamate-treated animals. No effects were seen in the hippocampal CA3 field. Our results strongly suggest a long-term induction of plastic changes in the cytoarchitecture of the hippocampal trisynaptic circuit neurons after cell death provoked by the monosodium glutamate-induced excitotoxicity. These plastic events as well as the aberrant expression of the glutamate NMDA receptors resulting from monosodium glutamate neonatal treatment could be strongly associated with the place learning impairments previously reported.

Prenatal-through-postnatal exposure to moderate levels of ethanol leads to damage on the hippocampal CA1 field of juvenile rats: a stereology and Golgi study.

Experimental paradigms conducted to assess the neurotoxic effects of ethanol exposure on hippocampus development have yielded controversial findings. Hippocampal CA1 population and some cytoarchitectural parameters of pyramidal cells were studied after exposure to ethanol during early development, in rats. Examination of 30-day-old offspring of rats exposed to moderate levels of ethanol during gestation through lactation showed an increased volume of the hippocampal CA1 field compared to untreated or pair-fed control pups, as well as a reduced number of pyramidal neurons. In addition, the number of spines from surviving CA1 pyramidal neurons was reduced. Furthermore, stubby and wide spines were proportionally increased, while the proportion of mushroom and ramified spines was reduced; no variation in the proportion of thin spines was observed. Because alcoholic women usually drink alcohol before, during, and after pregnancy, a broad-range experimental model of alcohol exposure was used in this study. The present findings show that experimental exposure to moderate levels of ethanol, resembling the human situation in alcoholic mothers, leads to loss of hippocampal CA1 pyramidal neurons, along with several pathological and plastic events in the dendritic arborization of these neurons. Some ethanol-induced excitotoxicity-related mechanisms, which may be underlying these effects, are discussed.

Neonatal exposure to monosodium glutamate disrupts place learning ability in adult rats.

The activation of glutamatergic NMDA receptors of the hippocampus is closely associated with expression of place learning. Neonatal exposure to monosodium glutamate leads to abnormal expression of NMDA receptor subunits in the hippocampus, but its effect on place learning is unknown. Place learning acquisition and retrieval were assessed in mature adult rats after subcutaneous injection of monosodium glutamate (4 mg/g body weight) in eight neonatal rat pups at postnatal days one, three, five, and seven. Eight untreated rats were used as controls. At four months of age, the rats were challenged over a period of nine days with a place learning task. The task used an acquisition-retrieval paradigm in a Morris maze. Place learning acquisition was impaired in the experimental rats, which were unable to reduce their escape latencies during the nine training days. Controls improved between the fifth and ninth days of training. Test trials showed that retrieval of spatial information was also impaired in the experimental animals. These results show that both place learning acquisition and retrieval abilities in mature rats are impaired by neonatal treatment with monosodium glutamate. These findings may be related to the abnormal expression of NMDA receptor subunits in the hippocampus.

Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre- and post-natal exposure to moderate levels of ethanol.

Migration of the external granular layer cells in the cerebellum of rats was delayed after exposure to moderate levels of ethanol during a pre-gestational period, through gestation and lactation until weaning. After ethanol withdrawal, cell soma and dendrites were observed to be larger in granule cells. Likewise, Bergmann glia showed several cytoarchitectonic features suggesting cell immaturity, as well as some apparent compensatory plastic responses after ethanol withdrawal. These effects may be due to ethanol impairing neurotrophin-mediated processes during cerebellar development that could lead to alterations in Purkinje cell structure and activity, and thereafter in the psychoneural functions in which the cerebellar cortex is involved.

Density, but not shape, of hippocampal dendritic spines varies after a seizure-inducing acute dose of monosodium glutamate in rats.

Dendritic spines are the main postsynaptic neuronal targets of excitatory inputs in cortical neurons, and both spine density and shape possess a well known adaptive synaptic-stimulation-dependent plastic capacity. Eighteen Sprague-Dawley adult male rats were used. Monosodium glutamate-treated rats (4 g/kg of body weight, i.p.) showed tonic and clonic epileptic seizures, as well as less dendritic spines in the apical arborization of their hippocampal CA1 pyramidal cells, compared to both control groups. No changes were seen in the proportional density of thin, stubby, mushroom-shaped, wide, or ramified spines between groups. Excessive glutamate-mediated excitatory activity on receptors could have led dendritic spines to shrink until they disappeared, while the spine-type proportion may be kept balanced as an adaptive response.

Place-learning, but not cue-learning training, modifies the hippocampal theta rhythm in rats.

Hippocampal theta activity accompanies behaviours such as running, swimming, head movements and spatially orientated responses in the rat. However, whether a relationship between this activity and information processing exists remains unclear. As place-learning depends on hippocampal integrity, whereas cue-learning does not, the hippocampal theta activity underlying each test was evaluated. Local CA1 hippocampal electroencephalograms (EEGs) were recorded over 6 days in a Morris maze for one place-learning test group of rats (n=10) and one cue-learning test group (n=8). The EEG of the corresponding test was taken during waking immobile, searching, and on-platform stages. The relative power (RP) values of EEGs were divided into 4-6.5Hz, 6.5-9.5Hz, and 9.5-12Hz frequency sub-bands. The place-learning training produced a separation of 4-6.5Hz and 6.5-9.5Hz sub-bands in searching and platform stages and a higher activity on the 6.5-9.5Hz sub-band during searching, compared with the basal record, while the cue-learning group did not show differences related either to the training or behavioural stage. As the motor activity and swimming velocity was similar in both groups, the results strongly suggest that the changes observed in theta activity reflect information processing by the hippocampus.

Cerebral GABA release and GAD activity in protein- and tryptophan-restricted rats during development.

To evaluate the effects on the GABAergic system, Wistar rats were raised on a chronically protein- and tryptophan-restricted diet with 8% protein, based on either Purina chow or corn. There was a significant decrease in both body and cerebral weight in the restricted animals compared with the control group fed with a 23% protein diet. In animals fed mainly corn, glutamic acid decarboxylase (GAD) activity increased significantly at the ages studied (14, 30, and 60 days) in the cerebral cortex and hippocampus. In the same way, gamma-aminobutyric acid (GABA) release decreased significantly in early life in both brain regions, then increased in 30-60-day-old animals corn-fed predominantly in the cerebral cortex. The reduction in GABA release may be attributable to a decrease in GABAergic cell density, which could induce an over-activation of 5-hydroxytryptamine (5-HTergic) receptors, leading in turn to the observed enhancement of GAD activity. Taken together, these results may represent a plastic response by GABAergic neurons to (5-HTergic under-stimulation in mainly corn-fed animals.

Cerebral serotonin depletion induces egocentric learning improvement in developing rats.

Egocentric learning ability of developing serotonin (5-HT)-depleted female rats was evaluated in the Morris maze test. 5-HT depletion was accomplished by a unique intracisternal injection of 5,7-dihydroxytriptamine at 21 days-old. A first behavioral test was applied before the lesion procedure. The animals were thereafter challenged to resolve the same test at 40 and 60 days-old. 5-HT depletion caused a dual effect on the rats' egocentric learning ability, i.e. at 40 days; control rats learned the task while the experimental rats were unable to learn it. At 60 days, control animals were unable to learn the test, while the experimental rats showed a successful performance. These results strongly suggest that 5-HT neurotransmission is necessary for egocentric learning establishment and regulation.

Neuroprotective effect of melatonin on brain damage induced by acute global cerebral ischemia in cats.

BACKGROUND: Melatonin has been proposed as a neuroprotective agent on the basis of its ability to function as a free radical scavenger, provided that lipoperoxidation and other free radical damage induced by reactive oxygen species resulting from cerebral ischemia are relevant pathophysiologic processes of ischemic neuronal damage. METHODS: The effects of melatonin or vehicle on neurologic deficit scores (Todd scale; maximal deficit score = 100, daily during 7 days after the ischemic episode) and neuronal population of hippocampal CA1-CA4 fields (cresyl violet stain, at the eighth day after the ischemic episode) were evaluated in adult male cats subjected to a 15-min period of acute global cerebral ischemia induced by cardiorespiratory arrest, and in cats subjected to a sham procedure. Continuous intravenous (iv) administration of either melatonin 10 mg/kg/h in 10% ethanol in saline or the vehicle alone (3 mL/kg/h) for 6 h starting 30 min after the end of the period of global cerebral ischemia was used as treatment. RESULTS: Global cerebral ischemia resulted in a severe loss of neurons in hippocampal CA1-CA4 fields (9, 13, 30 and 28% remaining neurons, respectively) of ischemic vehicle-treated cats in comparison with sham cats (100%). By contrast, remaining neurons in these regions were between 81 and 100% in the ischemic melatonin-treated cats, values that are nonsignificantly different as compared with sham cats. Values of remaining neurons in CA1-CA4 fields in ischemic melatonin-treated cats were significantly higher than those in ischemic vehicle-treated cats. Neurologic deficit scores in ischemic vehicle-treated cats (42-77 at day 1, 6-39 at day 7) were significantly higher than those in ischemic melatonin-treated cats (16-38 at day 1, 0-6 at day 7) on the days after the ischemic episode. CONCLUSIONS: Overall, the results support the neuroprotective effect of melatonin against the neuronal cerebral damage induced by acute global cerebral ischemia.

A tryptophan-deficient corn-based diet induces plastic responses in cerebellar cortex cells of rat offspring.

Sprague-Dawley male rats, fed with a tryptophan-deficient and 8% protein corn-based diet were compared with a group of animals fed with 8% protein alone, and with a group fed with Chow Purina containing 23% protein. Retardation of Bergmann glial cell maturation and a concomitant retardation in granule cell migration were observed in the corn-fed group at 21 days. At 30 days of age, the dendrites of granule cells of both hypoproteic and corn-fed groups were larger than those of the Chow-fed animals. At 60 days of age, dendritic arborization of Purkinje cells was more profuse in both the hypoproteic and corn-fed rats compared with the Chow-fed group. This retardation in granule cell migration could be partially due to Bergmann glial cell immaturity. Consequently, several plastic and maybe compensatory events in both granule and Purkinje cells could have occurred, due to tryptophan deficiency resulting from the corn-based diet.