Cerebellar synaptopathy in streptozotocin-induced diabetic rats / Sinaptopatía cerebelosa en ratas diabéticas inducidas por estreptozotocina

SUMMARY: There is an increasing amount of evidence that supports the diabetic complications of the central nervous system structure and function. The cerebellum, which is one of the primary structure derived from the hindbrain, plays an important role in motor control, motor coordination, and non-motor functions, such as cognitive processing. The synapse is a critical structure that regulates neuronal communication, and well-defined afferent and efferent fibre connections in the cerebellum help in maintaining the proper working order. Thus, the present study sought to investigate the long-term effects of diabetes-induced synaptopathy in the cerebellum, using both histological and ultrastructural studies. Twenty Sprague-Dawley male rats were divided randomly into control and diabetic groups, and diabetes was then induced through a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Six month later, the rats were sacrificed and the cerebellum was removed. Light and electron microscopic examinations showed a degeneration of Purkinje cells (Neuron purkinjense) with shrunken cells, pyknotic nuclei, and synaptopathy, including the reduction in synapse density, number of synaptic vesicles, and maturation of synapses in the molecular layer of diabetic cerebellum. The disruptions in synaptic profiles, which observed in the diabetic condition, could be related to cerebellar dysfunction, thus leading to the defects in coordinated movement, balance, as well as cognitive learning and memory.

RESUMEN: Actualmente existe una creciente evidencia que apoya las complicaciones diabéticas de la estructura y función del sistema nervioso central. El cerebelo, una de las estructuras primarias del cerebro posterior, desempeña un papel importante en el control motor, la coordinación motora y las funciones no motoras, tanto como en el procesamiento cognitivo. La sinapsis es una estructura crítica que regula la comunicación neuronal y las conexiones de fibras aferentes y eferentes bien definidas en el cerebelo, ayudan a mantener el funcionamiento correcto. Por lo tanto, en el presente estudio se investigaron los efectos a largo plazo de la sinaptopatía inducida por la diabetes en el cerebelo, utilizando estudios histológicos y ultraestructurales. Veinte ratas SpragueDawley macho se dividieron al azar en grupos de control y diabetes, se indujó la diabetes a través de una inyección intraperitoneal única de estreptozotocina (60 mg / kg de peso corporal). Seis meses después, se sacrificaron las ratas y se extrajo el cerebelo. Los exámenes de microscopías óptica y electrónica mostraron una degeneración de las neuronas purkinjenses (células de Purkinje), con células reducidas, núcleos picnóticos y sinaptopatía, como también la densidad reducida de sinapsis, el número de vesículas sinápticas y la maduración de las sinapsis en la capa molecular del cerebelo de las ratas diabéticas. Las interrupciones en los perfiles sinápticos, que se observaron en la condición diabética, podrían estar relacionadas con la disfunción cerebelosa, lo que lleva a defectos en el movimiento coordinado, el equilibrio, así como al aprendizaje cognitivo y la memoria.

Abiotrofia cerebelar em um gato: relato de caso / Cerebellar abiotrophy in a feline: case report

Um caso de abiotrofia cerebelar em um gato com 45 dias de idade foi diagnosticado no Laboratório de Patologia Animal, Hospital Veterinário da Universidade Federal de Campina Grande. O animal apresentava, havia 15 dias, apatia, anorexia, desidratação, ataxia, hipermetria, espasticidade dos membros torácicos e pélvicos, tremores de intenção, nistagmo, opistótono, déficit proprioceptivo e ausência de resposta de ameaça. Clinicamente, havia a suspeita de hipoplasia cerebelar, e, devido ao prognóstico desfavorável, o animal foi eutanasiado. Na necropsia, não foram observadas alterações macroscópicas. Microscopicamente, as lesões estavam restritas ao cerebelo e caracterizavam-se por alterações neurodegenerativas e necróticas, com desaparecimento segmentar dos neurônios de Purkinje. Nessas áreas, também se verificaram espaços em branco, denominado aspecto de cesto vazio, resultantes da perda dos neurônios de Purkinje, além de raros esferoides axonais e proliferação dos astrócitos de Bergmann. Em algumas áreas, a camada granular estava hipocelular e havia moderada gliose multifocal na camada molecular. O diagnóstico de abiotrofia cerebelar foi realizado com base nos dados epidemiológicos, clínicos e, principalmente, pelas alterações histopatológicas dos neurônios de Purkinje características da doença.(AU)

The aim of this report was to describe a case of cerebellar abiotrophy in cat with 45-year-old diagnosed at the Animal Pathology Laboratory, Veterinary Hospital of the Federal University of Campina Grande. The animal had presented 15-day apathy, anorexia, dehydration and neurological signs, characterized by ataxia, hypermetria, spasticity of fore and hindlimbs, intention tremor, nystagmus, opisthotonos, proprioceptive deficits, and absence of threat response. Clinically, cerebellar hypoplasia was suspected and the animal was euthanized due to poor prognosis. During necropsy, gross lesions were not observed. Microscopically the lesions were restricted to the cerebellum and were characterized by neurodegenerative and necrotic damage with segmental disappearance of the Purkinje cells. In these areas, there were also empty spaces, called the empty basket aspect, resulting from the loss of Purkinje cells, as well as rare axonal spheroids and proliferation of Bergmann's astrocytes. In some areas, the granular layer was hypocellular and there was moderate multifocal gliosis in the molecular layer. The diagnosis of cerebellar abiotrophy was based on epidemiological, clinical and mainly on histopathological changes in neurons of Purkinje disease characteristics.(AU)

Effect of gestational diabetes on neuronal cells in rat cerebellum in early postnatal life / Efecto de la diabetes gestacional sobre las células neuronales del cerebelo de ratas en el período postnatal

Previous study has shown the adverse effects of gestational diabetes on hippocampal neuronal density in animal model. This study was conducted to determine the effect of gestational diabetes on rat cerebellum in early postnatal life. In this experimental study, 10 dams randomly allocated into control and diabetic groups on day 1 of gestation. Five dams in diabetic group were administered 40 mg/kg/BW (intraperitoneally) of streptozotocin and control animals received normal saline. Six offspring of each gestational diabetes mellitus and controls were randomly selected at day 7 of postnatal life. Offspring were sacrificed and coronal sections were taken from the cerebellum and stained with cresyl violet. The number of Purkinje and granular cells and thickness of layers of cerebellum were evaluated by quantitative computer-assisted morphometric method. The Purkinje cells density at apex and depth of cerebellar lobules in the experimental group (14.40±0.7, 14.86±0.6) significantly reduced in comparison with the control group (16.72±0.3, 17.85±0.7) (P<0.05). The granular cell density at apex and depth of cerebellar lobules in the experimental group (23.94±0.6, 22.81±0.5) significantly reduced in comparison with the control group (29.20±0.8, 28.1±0.8) (P<0.05). The thickness of the Purkinje and internal granular and molecular layers at apex and depth of cerebellar cortex significantly reduced in diabetics group compared to controls (P<0.05). This study revealed that gestational diabetes induces loss of number and size of the Purkinje cells and the granular cells and reduction of thickness of the Purkinje and internal granular layer of the cerebellar cortex in neonatal mice.

Estudios previos han demostrado los efectos adversos de la diabetes gestacional sobre la densidad neuronal del hipocampo en modelos animales. Este estudio se realizó para determinar el efecto de la diabetes gestacional en el cerebelo de ratas durante la edad temprana postnatal. Fueron asignadas 10 ratas hembras al azar en grupos control y diabético en el primer día de gestación. Cinco en el grupo diabético recibieron una dosis de 40 mg/kg/Peso corporal de estreptozotocina (intraperitoneal) y los control una solución salina normal. Seis crías de cada una de las hembras del grupo diabetes mellitus gestacional y del grupo controles fueron seleccionados al azar el día 7 de vida postnatal. Fueron sacrificadas y se obtuvieron secciones coronales desde el cerebelo que fueron teñidas con violeta de cresilo. El número de células granulares de Purkinje y espesor de las capas de cerebelo fueron evaluadas por método morfométrico y ordenador cuantitativo. La densidad de células de Purkinje en el ápice y profundidad de los lóbulos del cerebelo en el grupo experimental (14,40±0,7 y 14,86±0,6) se redujeron significativamente en comparación con el grupo control (16,72±0,3 y 17,85±0,7) (P<0,05). La densidad de células granulares en el ápice y profundidad de los lóbulos del cerebelo en el grupo experimental (23,94±0,6 y 22,81±0,5) se redujo significativamente en comparación con el grupo control (29,20±0,8 y 28,1±0,8) (P<0,05). En el espesor de células Purkinje, las capas moleculares y granulares internas en el ápice y profundidad de la corteza del cerebelo, se observó una reducción significativa en el grupo diabéticos en comparación con los controles (P<0,05). Se observó que la diabetes gestacional induce la pérdida del número y tamaño de las células Purkinje y de células granulares, así como la reducción del espesor de las capas de Purkinje y granular interna de la corteza del cerebelo en ratones neonatos.

Histopathological and behavioral assessment of toxin-produced cerebellar lesion: a potent model for cell transplantation studies in the cerebellum

The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. In this experimental study, slow administration of quinolinic acid [QA, 5 microl of 200 micromol, 1 microl/minute] in the right cerebellar hemisphere [lobule VI] caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student's t test. The QA treated group showed marked motor learning deficits on the rotating rod test [p