Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, i... more Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, immobility episodes, epilepsy and paralysis of the hindlimbs, accompanied with differential expression of interleukins and their receptors that correlated with the progressive demyelination that characterize this mutant. Thus, the taiep rat is a suitable model to study neuroimmune alterations. The aim of this study was to investigate the immune alterations present in the mutant taiep rat during the acute infection with Trichinella spiralis. Our results show that there is an important decrease in the number of intestinal larvae in the taiep rat when compared to the Sprague-Dawley control rats. We also found differences in the percentage of innate and adaptive immune cell profile in the mesenteric lymphatic nodes and the spleen associated to the lack of myelin in the taiep rat. Finally, a clear pro-inflammatory cytokine pattern was seen in the infected taiep rat, which may explain the decre...
Hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) is a neurodegenerative d... more Hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H‐ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H‐ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II–IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H‐ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.
We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Spragu... more We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Sprague Dawley rats (SD). Taurine administration (50 mg/L drinking water) was provided to healthy pregnant SD rats at embryonic day 15 (E15) and afterward to the male offspring until eight months of age. We measured, in the offspring, the levels of nitric oxide (NO) through the Griess colorimetric reaction [1]; and malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) by the Gérard-Monnier technique [2]. The assessment ages for NO and MDA + 4-HDA were at postnatal day 15 (PND15), 1, 3, and 8 months of age. The body weight was measured as well as the integral motor behavior in the perinatal stage through the surface righting reflex test at PND5, cliff aversion test at PND9, grip strength test at PND 11, and front limb and hindlimb suspension tests at PND13. The tests were performed accordingly with [3]. The data obtained showed that SD rats with the taurine administration performed poorly in the motor tests compared with the untreated healthy rats. The taurine-treated rats also showed increased lipid peroxidation preferentially in cerebral nuclei involved in the motor activity, such as the medulla oblongata, the subcortical nuclei, and the cerebral cortex. However, the taurine treatment only increased NO concentration in the mentioned cerebral nuclei at older ages. Since taurine acts as an excitatory neuromodulator in the so-called gestational GABA-switch (occurring at E15) [4], the gestational increase in taurine concentration might generate excitotoxicity in healthy brains, which leads to impairments in the motor development of the offspring. Therefore, the present datasets can be valuable for researchers who attempt to use the taurine supplement on healthy animal models at gestational stages; and for research related to taurine intake during pregnancy in human patients. These datasets are related to the article "Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative str [...]
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegene... more Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegenerative disease due to mutations in the tubulin beta-4A (TUBB4A) gene, characterized by motor development delay, abnormal movements, ataxia, spasticity, dysarthria, and cognitive deficits. Diagnosis is made by integrating clinical data and radiological signs. Differences in MRIs have been reported in patients that carry the same mutation; however, a quantitative study has not been performed so far. Our study aimed to provide a longitudinal analysis of the changes in the cerebellum (Cb), corpus callosum (CC), ventricular system, and striatum in a patient suffering from H-ABC and in the taiep rat. We correlated the MRI signs of the patient with the results of immunofluorescence, gait analysis, segmentation of cerebellum, CC, and ventricular system, performed in the taiep rat. We found that cerebellar and callosal changes, suggesting a potential hypomyelination, worsened with age, in concomi...
We study the cognitive processing of visual working memory in three different conditions of memor... more We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain’s processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological modality. We use complex geometric polygons to assess visual working memory in a modified change detection task. Three different types of backgrounds were used to manipulate memory loading and 18 complex geometric polygons to manipulate stimuli configuration. The goal of our study was to test whether the memory load and configuration affect the correct-recall ratios. We expected that increasing visual items loading and changing configuration of items would induce differences in working memory performance. Brain activity related to the task was assessed through event-related potentials (ERP), during the test phase of each trial. Our results showed that visual items loading and changing of item configu...
Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counte... more Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counterflow has been hypothesized as a mechanism for brain cooling. Studies have shown that yawns are strongly associated with physiological and pathological conditions that increase brain temperature, and that they are followed by equivalent decreases in brain temperature. However, measured reductions in cranial or facial temperatures following yawning have yet to be reported, to our knowledge. To accomplish this, we used a subline of Sprague-Dawley rats that yawn at a much greater rate (20 yawns/h) than do outbred Sprague-Dawley rats (2 yawns/h). Using an infrared camera, we effectively evaluated thermal changes in the cornea and concha of these rats before, during, and after yawns. The maximum temperature in both regions significantly decreased 10 s following yawns (concha: -0.3 °C, cornea: -0.4 °C), with a return to basal temperatures after 20 s. This study is the first clear demonstration...
Despite the importance of rabbits in reproductive studies, little information is available on the... more Despite the importance of rabbits in reproductive studies, little information is available on the anatomy and participation of the striated-perineal muscles in male copulatory behavior. In our study, we describe the gross anatomy of two striated-perineal muscles: the ischiocavernosus (ICm) and the bulbospongiosus (BSm). Both muscles have their origin at the ischiadic arc, but the ICm is inserted into the penile crura and the BSm onto the ligamentum suspensorium of the penis. The motoneurons of both muscles were identified using retrograde labeling with horseradish peroxidase coupled to wheat-germ agglutinin. Motoneurons were dispersed in the lower-lumbar and upper-sacral spinal-cord segments, instead of being aggregated in the neuronal nucleus as in other species: the rat, mouse, gerbil, cat, and man. Bilateral dennervation of the ICm or BSm or both in sexually experienced male rabbits did not affect copulatory variables measured at 10, 20, and 30 days after surgery. However, muscular dennervation produced extravaginal ejaculations in 42% of copulatory tests and no ejaculation in 7% of tests, although male pelvic thrusting occurred. These results suggest the participation of the ICm and BSm perineal muscles in penile orientation during copulation but not in seminal emission as described in other mammalian species.
Sexual behavior declines with age in male rats. The rate and magnitude of this decline may depend... more Sexual behavior declines with age in male rats. The rate and magnitude of this decline may depend on the amount of prior sexual experience and a number of other, unidentified factors. Age-dependent changes in the characteristics of ejaculate quality in rats have not been described earlier, and the relationship between such changes and modifications of sexual behavior is likewise unknown. We have recently developed a technique for the detailed analysis of parameters of ejaculate in rats, and this technique was used for the determination of semen and seminal plug characteristics in rats of different ages. Sexually experienced Wistar rats were tested for sex behavior at the ages of 3, 12 and 24 months. Semen was obtained from the female partner immediately after ejaculation at these tests. Between tests, the males were offered the opportunity to copulate once every 3-4 weeks. The behavioral data showed that the latency to ejaculation was increased only at 24 months. Concerning the char...
... este panteones supu-ne que no existe una respuesta ante esti-nutlns sexuales sostenidos tras ... more ... este panteones supu-ne que no existe una respuesta ante esti-nutlns sexuales sostenidos tras la eyamia' non E11 ou-as palabras 1a mujer, puede [IEEE de le fase orgúsmiea, u una las': de rnttauta y nuevamente a urn fine ctgíflml» n. Esta aituattiúu Mas-tora} I-ialïuhan m
Tubulinopathies are a group of recently described diseases characterized by mutations in the tubu... more Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.
Infertility and reproductive problems have been reported in women with several neurological disor... more Infertility and reproductive problems have been reported in women with several neurological disorders, for example, demyelination. However, the physiology of such problems has remained unknown so far. The taiep rats are an animal neurological model that initially shows a hypomyelination followed by a progressive demyelination of the central nervous system. This animal has reproductive problems, and the aim of this work is to characterize the follicular development, secretion of ovarian hormones, and presence of noradrenaline in the ovaries of the female taiep rats in the juvenile and adult stages. The taiep rats have low body weight (approximately 19% less than that of SD rats), a delay of 4 days in the age of vaginal opening, and an irregularity in the estrous cycle by the absence or prolongation of some estral cycle stage. In the juvenile stage, we observed a decrease of approximately 44% in the total number of follicles with a 15% increase of atresia and an 80% decrease in the fl...
Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an... more Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morpho...
Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, i... more Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, immobility episodes, epilepsy and paralysis of the hindlimbs, accompanied with differential expression of interleukins and their receptors that correlated with the progressive demyelination that characterize this mutant. Thus, the taiep rat is a suitable model to study neuroimmune alterations. The aim of this study was to investigate the immune alterations present in the mutant taiep rat during the acute infection with Trichinella spiralis. Our results show that there is an important decrease in the number of intestinal larvae in the taiep rat when compared to the Sprague-Dawley control rats. We also found differences in the percentage of innate and adaptive immune cell profile in the mesenteric lymphatic nodes and the spleen associated to the lack of myelin in the taiep rat. Finally, a clear pro-inflammatory cytokine pattern was seen in the infected taiep rat, which may explain the decre...
Hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) is a neurodegenerative d... more Hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H‐ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H‐ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II–IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H‐ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.
We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Spragu... more We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Sprague Dawley rats (SD). Taurine administration (50 mg/L drinking water) was provided to healthy pregnant SD rats at embryonic day 15 (E15) and afterward to the male offspring until eight months of age. We measured, in the offspring, the levels of nitric oxide (NO) through the Griess colorimetric reaction [1]; and malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) by the Gérard-Monnier technique [2]. The assessment ages for NO and MDA + 4-HDA were at postnatal day 15 (PND15), 1, 3, and 8 months of age. The body weight was measured as well as the integral motor behavior in the perinatal stage through the surface righting reflex test at PND5, cliff aversion test at PND9, grip strength test at PND 11, and front limb and hindlimb suspension tests at PND13. The tests were performed accordingly with [3]. The data obtained showed that SD rats with the taurine administration performed poorly in the motor tests compared with the untreated healthy rats. The taurine-treated rats also showed increased lipid peroxidation preferentially in cerebral nuclei involved in the motor activity, such as the medulla oblongata, the subcortical nuclei, and the cerebral cortex. However, the taurine treatment only increased NO concentration in the mentioned cerebral nuclei at older ages. Since taurine acts as an excitatory neuromodulator in the so-called gestational GABA-switch (occurring at E15) [4], the gestational increase in taurine concentration might generate excitotoxicity in healthy brains, which leads to impairments in the motor development of the offspring. Therefore, the present datasets can be valuable for researchers who attempt to use the taurine supplement on healthy animal models at gestational stages; and for research related to taurine intake during pregnancy in human patients. These datasets are related to the article "Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative str [...]
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegene... more Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegenerative disease due to mutations in the tubulin beta-4A (TUBB4A) gene, characterized by motor development delay, abnormal movements, ataxia, spasticity, dysarthria, and cognitive deficits. Diagnosis is made by integrating clinical data and radiological signs. Differences in MRIs have been reported in patients that carry the same mutation; however, a quantitative study has not been performed so far. Our study aimed to provide a longitudinal analysis of the changes in the cerebellum (Cb), corpus callosum (CC), ventricular system, and striatum in a patient suffering from H-ABC and in the taiep rat. We correlated the MRI signs of the patient with the results of immunofluorescence, gait analysis, segmentation of cerebellum, CC, and ventricular system, performed in the taiep rat. We found that cerebellar and callosal changes, suggesting a potential hypomyelination, worsened with age, in concomi...
We study the cognitive processing of visual working memory in three different conditions of memor... more We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain’s processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological modality. We use complex geometric polygons to assess visual working memory in a modified change detection task. Three different types of backgrounds were used to manipulate memory loading and 18 complex geometric polygons to manipulate stimuli configuration. The goal of our study was to test whether the memory load and configuration affect the correct-recall ratios. We expected that increasing visual items loading and changing configuration of items would induce differences in working memory performance. Brain activity related to the task was assessed through event-related potentials (ERP), during the test phase of each trial. Our results showed that visual items loading and changing of item configu...
Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counte... more Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counterflow has been hypothesized as a mechanism for brain cooling. Studies have shown that yawns are strongly associated with physiological and pathological conditions that increase brain temperature, and that they are followed by equivalent decreases in brain temperature. However, measured reductions in cranial or facial temperatures following yawning have yet to be reported, to our knowledge. To accomplish this, we used a subline of Sprague-Dawley rats that yawn at a much greater rate (20 yawns/h) than do outbred Sprague-Dawley rats (2 yawns/h). Using an infrared camera, we effectively evaluated thermal changes in the cornea and concha of these rats before, during, and after yawns. The maximum temperature in both regions significantly decreased 10 s following yawns (concha: -0.3 °C, cornea: -0.4 °C), with a return to basal temperatures after 20 s. This study is the first clear demonstration...
Despite the importance of rabbits in reproductive studies, little information is available on the... more Despite the importance of rabbits in reproductive studies, little information is available on the anatomy and participation of the striated-perineal muscles in male copulatory behavior. In our study, we describe the gross anatomy of two striated-perineal muscles: the ischiocavernosus (ICm) and the bulbospongiosus (BSm). Both muscles have their origin at the ischiadic arc, but the ICm is inserted into the penile crura and the BSm onto the ligamentum suspensorium of the penis. The motoneurons of both muscles were identified using retrograde labeling with horseradish peroxidase coupled to wheat-germ agglutinin. Motoneurons were dispersed in the lower-lumbar and upper-sacral spinal-cord segments, instead of being aggregated in the neuronal nucleus as in other species: the rat, mouse, gerbil, cat, and man. Bilateral dennervation of the ICm or BSm or both in sexually experienced male rabbits did not affect copulatory variables measured at 10, 20, and 30 days after surgery. However, muscular dennervation produced extravaginal ejaculations in 42% of copulatory tests and no ejaculation in 7% of tests, although male pelvic thrusting occurred. These results suggest the participation of the ICm and BSm perineal muscles in penile orientation during copulation but not in seminal emission as described in other mammalian species.
Sexual behavior declines with age in male rats. The rate and magnitude of this decline may depend... more Sexual behavior declines with age in male rats. The rate and magnitude of this decline may depend on the amount of prior sexual experience and a number of other, unidentified factors. Age-dependent changes in the characteristics of ejaculate quality in rats have not been described earlier, and the relationship between such changes and modifications of sexual behavior is likewise unknown. We have recently developed a technique for the detailed analysis of parameters of ejaculate in rats, and this technique was used for the determination of semen and seminal plug characteristics in rats of different ages. Sexually experienced Wistar rats were tested for sex behavior at the ages of 3, 12 and 24 months. Semen was obtained from the female partner immediately after ejaculation at these tests. Between tests, the males were offered the opportunity to copulate once every 3-4 weeks. The behavioral data showed that the latency to ejaculation was increased only at 24 months. Concerning the char...
... este panteones supu-ne que no existe una respuesta ante esti-nutlns sexuales sostenidos tras ... more ... este panteones supu-ne que no existe una respuesta ante esti-nutlns sexuales sostenidos tras la eyamia' non E11 ou-as palabras 1a mujer, puede [IEEE de le fase orgúsmiea, u una las': de rnttauta y nuevamente a urn fine ctgíflml» n. Esta aituattiúu Mas-tora} I-ialïuhan m
Tubulinopathies are a group of recently described diseases characterized by mutations in the tubu... more Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.
Infertility and reproductive problems have been reported in women with several neurological disor... more Infertility and reproductive problems have been reported in women with several neurological disorders, for example, demyelination. However, the physiology of such problems has remained unknown so far. The taiep rats are an animal neurological model that initially shows a hypomyelination followed by a progressive demyelination of the central nervous system. This animal has reproductive problems, and the aim of this work is to characterize the follicular development, secretion of ovarian hormones, and presence of noradrenaline in the ovaries of the female taiep rats in the juvenile and adult stages. The taiep rats have low body weight (approximately 19% less than that of SD rats), a delay of 4 days in the age of vaginal opening, and an irregularity in the estrous cycle by the absence or prolongation of some estral cycle stage. In the juvenile stage, we observed a decrease of approximately 44% in the total number of follicles with a 15% increase of atresia and an 80% decrease in the fl...
Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an... more Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morpho...
Uploads
Papers by Jose R Eguibar