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Objective:To investigate the long-term alcohol consumption on synaptic plasticity of mossy fiber-granule cells in cerebellar cortex and motor coordination function in mice.Methods:Thirty healthy male ICR mice aged 6-8 weeks were divided into saline group (control group)and alcohol consumption group(alcohol group) according to random number table with 15 in each group. The mice in alcohol group were injected intraperitoneally with 15% ethanol (1.6 g/kg), while the mice in control group were injected with the same volum of normal saline, all mice were injected intraperitoneally once a day for 28 consecutive days. Walking obstacle test and rotating rod fatigue test were used to observe the motor coordination ability and learning ability of mice. Electrophysiological patch clamp technique was used to detect the field potential changes of long-term synaptic plasticity induced by blowing stimulation. SPSS 22.0 software was used for statistical analysis.Independent sample t-test, paired t-test and repeated measurement analysis of variance were used for comparison between the two groups before and after intervention. Results:The electrophysiological results showed that the amplitude percentage of field potential N1 wave in the control group after blowing stimulation was (130.4±3.3)%, which was higher than that before stimulation ((100.6±2.7)%) ( t=27.07, P<0.01). And the percentage of area under N1 standardized waveform after stimulation ((128.8±4.5)%) was greater than that before stimulation ((100.2±3.5)%) ( t=19.43, P<0.01). There was no significant difference in the amplitude percentage of N1 wave in alcohol group ((97.8±4.3)%) after blowing stimulation compared with that before stimulation ((99.5±5.6)%) ( t=0.93, P>0.05). And also there was no significant difference in the area percentage under N1 wave after stimulation ((96.8±3.6)%) compared with that before stimulation ((100.2±4.2)%) ( t=2.38, P>0.05). The results of walking obstacle test showed that the total number of errors (3.14±0.19) in the alcohol group was higher than that in the control group(1.52±0.29) ( t=17.87, P<0.01), and the total error time ((63.85±9.34) ms) was longer than that in the control group ((28.93±7.21) ms) ( t=11.45, P<0.01). The results of repeated measurement analysis of variance showed that there was an interaction between time and group in the falling speed and falling latency of the two groups of mice in the rotating rod fatigue experiment ( F=4.5, 455.1, both P<0.05). The drop speed of mice in the alcohol group was significantly lower than that in the control group from day 1 to 7 (all P<0.05). The fall latency of mice in the alcohol group from day 1 to 7 was shorter than that in the control group, and the difference was statistically significant (all P<0.05). Conclusion:Long-term alcohol consumption impairs synaptic plasticity in the granular layer of mice and leads to a significant decline in motor coordination and motor learning ability.
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Ethanol is one of the most widely used and abused psychoactive substances in the world. Long-term and excessive intake of alcohol can damage the central nervous system and lead to impairment of its function. As an important component of the central nervous system, cerebellum is one of the main target organs damaged by ethanol. Acute and chronic ethanol intake can damage human motor coordination, motor learning and some cognitive functions. Its damage mechanism is generally believed to be caused by the abnormal function of cerebellar cortical neural circuit caused by ethanol intake. Combined with recent studies on the mouse model of long-term ethanol intake, this article reviews the cerebellar neural network mechanism of long-term ethanol intake from various aspects, with a view to providing research and development in behavioral movement, motor coordination, cognitive function, depression, and offers new ideas with the rise of precision medicine for treatment. People are increasingly interested in exploring the mechanism of long-term ethanol intake on the cerebellar neural network. How to improve or block the corresponding mechanism based on the mechanism of action found in existing research is an important proposition in future research.
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Objective@#To investigate the expression and potential role of heterogeneous nuclear ribonucleo-protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma.@*Methods@#The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A-IP-qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells.@*Results@#The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment.@*Conclusions@#HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up-regulated at transcriptional level but obviously down-regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin-proteasome pathway may account for the down-regulation of HNRNPA2B1 at protein level.
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Se realizó un estudio descriptivo y transversal de la corteza cerebelosa humana, desde el punto de vista histomorfométrico, desde enero hasta septiembre del 2015, con el empleo de la microscopia holográfica digital instalada en el Departamento de Holografía Digital de la Universidad de Oriente en Santiago de Cuba, con vistas efectuar mediciones que permitieran establecer comparaciones con otros estudios. Los cálculos mostraron el grosor de las capas molecular y granulosa, el área, el perímetro, los diámetros mayores y menores del cuerpo y el núcleo de las células de Purkinje. Asimismo, se tomaron imágenes holográficas en tres dimensiones, que posibilitaron concluir la existencia de parámetros determinados mediante este procedimiento, los que no habían sido notificados y que resultan de interés en el estudio histológico de la corteza cerebelosa
A descriptive and cross-sectional study of the human cerebellar cortex, from the histomorphometric point of view, was carried out from January to September, 2015, using the digital holographic microscopy installed in the Digital Holography Department of Oriente University in Santiago de Cuba, aimed at making measurings that allowed to establish comparisons with other studies. The calculations showed the thickness of the molecular and granular layers, the area, perimeter, greatest and smallest diameters of the body and Purkinje cells nucleus. Also, holographic images in three dimensions were taken, that facilitated to conclude the existence of certain parameters by means of this procedure, those that had not been notified and are of interest in the histological study of the cerebellar cortex
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Humans , Male , Female , Holography , Cerebellar Cortex , Cerebellum/ultrastructure , Epidemiology, Descriptive , Cross-Sectional StudiesABSTRACT
Background: There has been an ever increasing use of liquid vaporizers as residential insecticides to get rid of the problem of mosquito and as a concern shown towards prevention of increasing cases of vector borne diseases. Adverse impact of these chemicals are many including giddiness, nausea, headache, body ache, lethargy and dizziness but the current research on the safety of these chemical compounds is market driven and proper histological studies that can establish their toxic effects on cerebellar cortex which acts as higher centre of coordination, balance and learning are rare. Accordingly the present study was planned to look into the claim of safety of these inhalational compounds and to establish the correlation, if any between pyrethroid based mosquito repellent inhalational use and the histological insult to the cerebellum of Albino rats. Methods: Total of twenty albino rats were marked into groups marked as control and experimental. The exposure of experimental group was carried out to 3.2% w/v prallethrin vapours for total of 12 hours in a day and continued for 180 days. The Albino rats in control group were put in similar surroundings but without exposure to any mosquito repellent. The albino rats were killed after completing exposure of 180 days. The rats brain was dissected and Cerebellum was taken out. Tissue processing and sectioning done and finally stained wusing haematoxylin, eosin and thionin stains. Results: Outer molecular and inner granular layer of cerebellum showed areas of degeneration with disruption and decreased density of cells in Purkinje cell layer. Conclusions: The findings of the study do confirms that mosquito repellents given by inhalational route leads to toxic insult as evident in this study on Albino rats on long term exposure of 180 days as shown by histological alterations in the sections of cerebellar cortex of rat CNS.
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Background: The cerebellum, also called the little brain is an organ concerned with regulation of movement and other associated motor functions. It is believed to be phylogenetically one of the oldest parts of the brain. It accounts for one tenth of the brain volume and contains approximately 50% of the total brain neuron. Damage to the cerebellum is major factor involved in the progression of movement disorders. Aim: To investigate possibility of selective neuronal vulnerability in neurotoxicity and the etiology of neurodegenerative diseases especially those involving movement disorders originating from the cerebellum. Method: F1 Generation adult Wistar rats were treated with 20 and 10 mg/Kg BW of potassium cyanide (KCN), the cerebellar cortex was harvested and processed for immunohistochemistry of cell cycle markers (anti-p53 and anti-Bax) and the neuronal glycolytic pathway marker; Neuron Specific Enolase (anti-NSE). Antigen retrieval method was used specifically as peroxidase anti peroxidase reaction (PAP). The reaction was developed using a polymer 3’3’Diaminobenzidine tetrachloride (DAB), intensified in Methenamine Silver and counterstained in Hematoxylin. Results: Cyanide toxicity induced apoptosis in the cerebellum via a pathway involving Bax in mitochondria dysregulation (mitochondria apoptotic signaling) and a cytoplasmic pathway involving p53 (a nucleolase). The NSE expression level also indicates associated metabolic dysregulation with alteration in expression of cell cycle proteins. Conclusion: Cyanide toxicity induced cell death in the cerebellar cortex by metabolic alteration (NSE) and ROS formation. The expression of Bax and p53 showed that apoptosis was triggered via a mitochondria/Bax dependent, p53 related apoptotic pathway.
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Purpose: This study assessed some microstructural effects of quinine; commonly used in malaria chemotherapy; especially in chloroquine-resistant and cerebral malaria; on the Nissl substance in the cerebellar cortex of adult Wistar rats using microanatomical studies. Methods: Twenty seven adult male Wistar rats; weighing between 150g and 190g; were randomly separated into groups A; B and C (n=9). The rats in group A served as the control and received intramuscular injection of physiological saline. Group B rats were injected intramuscularly with liquid quinine; 16mg/kg body weight as a start dose; followed by 8mg/kg body weight 8 hourly for seven days. Group C rats received the same treatment as group B but were subjected to a withdrawal period of one week. Groups A and B rats were sacrificed at the end of the treatment while group C rats were sacrificed at the end of one week. The cerebellum of each rat was removed and fixed in 10formol saline for histological analysis. Results: The findings showed that the Nissl substances in the cerebellar cortex in control rats stained more intensely and distinctly compared with the less intense stain and degenerated Nissl substances in the treated rats.Conclusion: The observed degenerative changes in the Nissl substances in the cerebellar cortex of the treated rats may affect the synthesis of proteins in correlation with neuronal functions
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Humans , Cerebellar Cortex , Malaria/therapy , Nigeria , Nissl Bodies , QuinineABSTRACT
@#Objective To investigate the effects of estrogen on brain derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) levels in cerebellar cortex of ovariectomized rats. Methods 24 female Wistar rats were randomly divided into three groups: intact (INT) group, ovariectomized (OVX) group, and OVX+estrogen 0.5 mg/kg every day group (E group). Radioimmunoassay (RIA) was used to measure the estrogen content in plasma, and the levels of BDNF and NPY were measured with Immunohistochemistry. Results Compared with the INT group, the plasma estrogen level significantly reduced in OVX group (P<0.001). However, the plasma estrogen level was higher in the E group than that in the OVX group (P<0.001). The BDNF and NPY presented in the Purkinje cell layer,and BDNF also distributed in the molecular layer and granular layer. Compared with that in the INT group, BDNF and NPY positive cells markedly decreased in OVX group, with slight cytosol staining in the cerebellar cortex (P<0.001). The BDNF and NPY positive neurons increased in E group compared with that in the OVX group (P<0.001). Conclusion Estrogen can increase the BDNF and NPY levels in cerebellar cortex of female rats, which may protect the structure and function of cerebellar neurons.
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Early postnatal period is considered as the critical period for formation and maturation of the synapses. And cerebellum has the major role in the development of equilibrium and somatic motor function, especially in the early postnatal age. So, I performed this study to investigate the morphological changes of the synapses in the rat cerebellar cortex. Sprague-Dawley rats were used as experimental animals. The ultrastructure of Synapses was observed in six groups ; 3-day, 1-week, 2-week, 3-week, 4-week, 5-week. The results are as followes. 1. After birth, the synaptic density was increased gradually by the forth week. 2. The length of postsynaptic densities was increased significantly in the period between first and second week. 3. There was significant correlation between the length of postsynaptic densities and the area of synaptic vesicle clusters. 4. The frequency of asymmetric and/or frown synapses was increased dramatically with advancing ages. According to the above results, the synaptogenesis in the rat cerebellum is very active in their early postnatal periods. And asymmetric and/or active frown synapses were the major type of synapses with advancing ages.
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Animals , Rats , Cerebellar Cortex , Cerebellum , Critical Period, Psychological , Parturition , Post-Synaptic Density , Rats, Sprague-Dawley , Synapses , Synaptic VesiclesABSTRACT
Severe irradiation on head may result functional alterations of central nervous system. In this study, the irradiation effect on the cerebellar cortex following heavy X-irradiation on head was studied ultrastructurally. Radiation was produced with the linear accelerator ML-4MV[Mitshubishi Co.], and rats weighing about 200gm each were exposed their heads within the radiation areas of 30cm x 30cm, under the radiation distance of 80cm, and with the radiation depth of 1.2 cm. Radiation doses were 3,000rads or 6,000rads, respectively. Animals were sacrificed on 6 hours, 2 days or 6 days following the radiation. Under anesthesia, animals were perfused with 1% glutaraldehyde-1% paraformaldehyde solution. Two hours after the perfusion, brain were taken out and refixed over night in the perfusion fixative. Small blocks of cerebellar hemispheric cortices were refixed 2 hours in 2% osmium tetroxide solution. Fixed tissues were dehydrated in alcohol, embedded in araldite mixture, and cut with ultratome. Ultrathin sections were contrasted with uranyl acetate and lead citrate solutions, and observed with electron microscope. The results obstained were as follow : 1. On 6th hour following X-irradiations, many cerebellar cortical neurons showed increased electron densities, more complicated nuclear infoldings, depletion of synaptic vesicles, expansion of astroglial territories, etc. 2. On 2nd day following X-irradiations, many organelle-rich cells such as Purkinje cells and Golgi cells were darkly degenerated. Numerous myelin figures formed by the cisternal fusions of Golgi apparatus or granular endoplasmic reticula were observed. Cytoplasmic processes of activated astroglial cells were expanded around capillaries and between granule cells. 3. On 6th day following X-irradiations, morphology of neuropil and neurones in the cerebellar cortex was generally restored, except the expanded territories of astroglial cells. From the above results, it was concluded that the release ofneurotransmitters and transcapillary leakage of blood substance were occurred on 6 hours after heavy X-irradiations. And severe alterations were produced on 2 day after X-irradiation, but the condition was generally restored on 6th day following X-irradiation.
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Animals , Rats , Anesthesia , Brain , Capillaries , Central Nervous System , Cerebellar Cortex , Citric Acid , Cytoplasm , Golgi Apparatus , Head , Myelin Sheath , Neurons , Neuropil , Osmium Tetroxide , Particle Accelerators , Perfusion , Purkinje Cells , Radiation Effects , Synaptic VesiclesABSTRACT
A comparative study of the distribution of a simple esterase and acetylcholinesterase in the cerebellar cortex of mouse and bat has been made. The Purkinje layer is intensely positive for simple esterase in both species. The granular and molecular layers showed mild to moderate activity in mouse and intense activity in bat. Acetylcholinesterase in cerebellar layers of bat is more intense than in mouse. In bat cerebellum, acetylcholinesterase is observed in the dendrites of Purkinje cells, but not in their cell bodies. Acetylcholinesterase was not found in Purkinje cells of mouse.
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A cerebellar afferent connection from the periaqueductal grey (PAG) has been demonstrated in the rat by means of retrograde transport of horseradish peroxidase (HRP) in the present study. The projection is bilateral, but the projection from the ipsilateral side is predominant (3:1). Its main origin is the ventromedial and ventrolateral regions of middle and caudal parts of PAG (98.8％), and the fibers reach different cerebellar cortical regions: culmen, declive, folium vermis, tuber vermis, pyramis vermis, uvula vermis, lobulus quadrangularis, crus Ⅰ, crus Ⅱ, and paraflocculus. Most labelled neurons are medium sized, but some small neurons also appear to project to cerebellum. Only a few large neurons are retrogradely labelled at the most caudal end of the caudal part. Functionally, both cerebellum and PAG are related to visceral activities. Consulting the present experiment, we discussed the significant role of the PAG-cerebellar projection.