Loki-lobuluko epilepsiaren animalia-eredu batean hipokanpo mailan gertatzen diren aldaketak: hipokanpoaren mendeko portaerak, endokannabinoide sistema eta astrozitoak

28 p.[EU] Ikerketa honen helburua, alde batetik, loki-lobuluko epilepsiaren animalia-eredu batean hipokanpoaren mendekoak diren portaeren aldaketak aztertzea da. Horrela, oroimenean eta habia egiteko gaitasunean dituen eraginak neurtuko dira. Beste alde batetik, maila zelularrean gertatzen diren aldaketak aztertuko dira, CB1 hartzailearen adierazpenean eta astrozitoetan gertatzen diren aldaketetan arreta jarriz. Mikroskopio elektronikorako teknika immunozitokimikoak erabiliko dira astrozitoetan gertatzen diren CB1 hartzailearen aldaketak zehazteko

CB1 hartzaile endokannabinoidearen eta astrozitoen aldaketak loki-lobuluko epilepsiaren animalia-eredu batean

[EUS] Loki-lobuluko epilepsia (LLE) askotan epilepsiaren aurkako medikamenduekin trataezina den epilepsia partzial mota bat da. LLEn ez-ohiko neurona-jarduera, besteak beste, hipokanpoan gertatzen da. LLEdun pazienteetan oroimen arazoak eta depresioa jasateko probabilitate handia ikusi dira. Horrez gain, endokannabinoide (eKB) sisteman aldaketak aurkezten dituzte, eta astrozitoen hipertrofia eta hiperplasia ere agertzen dituzte. Lan honetan, LLEren animalia-eredu batean aztertu dira hipokanpoaren mendekoak diren antsietatea, oroimena eta habia egiteko gaitasuna, eta hipokanpoan gertatzen diren CB1 hartzaileen adierazpenaren eta astrozitoen aldaketak. Hiru animalia talde konparatu ditugu: kontrolak eta epilepsia-krisi arinak eta larriak izan dituztenak. Hirurekin portaera-probak burutu dira antsietate-maila eta memoria-espaziala aztertzeko, eta euren habiak aztertu dira. Azkenik, argi mikroskopiaren bidez animalien hipokanpoa aztertzeko prozedura immunohistokimikoak burutu dira. Ikusi dugu krisi epileptiko larriak izan dituzten animaliek memoria-espaziala kaltetuta dutela; izan ere, oroimen-proban denbora gehiago behar dute, akats gehiago egiten dituzte eta ez dute bilaketa-estrategiarik garatzen. Maila mikroskopikoan, hipokanpoko CA1 eskualdean, CB1 hartzaile askoz gutxiago aurkezten dituzte eta astrozitoen hiperplasia eta hipertrofia agertzen dituzte. Emaitzek erakusten dute LLEk oroimen-espazialean eragin kaltegarriak dituela eta, beraz, aztertu daitekeen ezaugarri bat dela LLEk eragindako kalteak detektatzeko. Bestalde, CA1 eskualdean astrozitoen eta CB1 hartzaileen aldaketak sortzen ditu, eta baliteke horiek oroimen-urritasunaren eta krisi epileptikoen larritasun mailarekin erlazionatuta egotea. Euskara[EN] Temporal lobe epilepsy (TLE) is a type of partial epilepsy which is often resistant to anti-epileptic drugs. In TLE, unconventional neuronal activity takes place, in the hippocampus among other brain areas. TLE patients frequently show memory disorders and they are more likely to suffer from depression. Moreover, they usually present alterations in the endocannabinoid (eCB) system as well as astrocytic hypertrophy and hyperplasia. A TLE animal model was used to examine hippocampal dependant behaviours such as anxiety, spatial memory and nesting, and hippocampal changes in the expression of CB1 receptors and astrocytes. Three animal groups were compared: controls and animals which have suffered mild and severe epileptic seizures. In the three groups behavioral tests were conducted to analyse the degree of anxiety, spatial memory and their nests. Lastly, immunocitochemistry procedures were performed to study the hippocampus at light microscopy. We saw that animals who have suffered severe epileptic seizures have spatial memory impairment as they need more time in the memory test, they make more mistakes and they do not develop any strategy. At microscopic level, in the CA1 hippocampus region there is lower expression of CB1 receptors and there are astrocytic hypertrophy and hyperplasia. These results demonstrate that TLE impairs spatial memory, thus, it is an analysable feature that can be used to detect the damages caused by TLE. Furthermore, TLE causes changes in the CB1 receptors and astrocytes from the CA1 region and those alterations might be related to the memory impairment and the severity of the seizures. Ingelera[ES] La epilepsia (LLE) del lóbulo local es un tipo de epilepsia parcial que muchas veces es intratable con medicamentos anti epilepsia. En LLE la actividad neuronal no convencional tiene lugar, entre otras cosas, en el hipocampo. En los pacientes con LLE se han detectado problemas de memoria y alta probabilidad de sufrir depresión. Además presentan cambios en el sistema endocannabinoide (eKB) e incluyen hipertrofia e hiperplasia de los astrocitos. En este trabajo se analiza en un modelo animal de la LLE la ansiedad, la memoria y la capacidad de nidificación, dependientes del hipocampo, así como los cambios en la expresión y en los astrocitos de los receptores CB1 que se producen en el hipocampo. Hemos comparado tres grupos de animales que han sufrido controles y ataques de epilepsia leves y graves. Con los tres se han realizado pruebas de comportamiento para analizar el grado de ansiedad y la memoria espacial y analizar sus nidos. Finalmente, se han llevado a cabo procedimientos inmunohistoquímicos para el estudio del hipocampo animal mediante microscopía de luz. Hemos visto que los animales que han sufrido graves crisis epilépticas tienen dañada la memoria espacial, ya que necesitan más tiempo en la prueba de memoria, cometen más errores y no desarrollan estrategias de búsqueda. A nivel microscópico, en la región hipocampo CA1 presentan muchos menos receptores CB1 y presentan hiperplasia e hipertrofia de los astrocitos. Los resultados muestran que la LLE tiene efectos nocivos sobre la memoria espacial y que, por tanto, es una característica analizable para detectar los daños producidos por la LLE. Por otra parte, en la región CA1 se producen cambios en los astrocitos y receptores CB1 que pueden estar relacionados con el grado de inmemoria y la gravedad de las crisis epilépticas

CB1 hartzaile endokannabinoidearen eta astrozitoen aldaketak loki-lobuluko epilepsiaren animalia-eredu batean

[EUS] Loki-lobuluko epilepsia (LLE) askotan epilepsiaren aurkako medikamenduekin trataezina den epilepsia partzial mota bat da. LLEn ez-ohiko neurona-jarduera, besteak beste, hipokanpoan gertatzen da. LLEdun pazienteetan oroimen arazoak eta depresioa jasateko probabilitate handia ikusi dira. Horrez gain, endokannabinoide (eKB) sisteman aldaketak aurkezten dituzte, eta astrozitoen hipertrofia eta hiperplasia ere agertzen dituzte. Lan honetan, LLEren animalia-eredu batean aztertu dira hipokanpoaren mendekoak diren antsietatea, oroimena eta habia egiteko gaitasuna, eta hipokanpoan gertatzen diren CB1 hartzaileen adierazpenaren eta astrozitoen aldaketak. Hiru animalia talde konparatu ditugu: kontrolak eta epilepsia-krisi arinak eta larriak izan dituztenak. Hirurekin portaera-probak burutu dira antsietate-maila eta memoria-espaziala aztertzeko, eta euren habiak aztertu dira. Azkenik, argi mikroskopiaren bidez animalien hipokanpoa aztertzeko prozedura immunohistokimikoak burutu dira. Ikusi dugu krisi epileptiko larriak izan dituzten animaliek memoria-espaziala kaltetuta dutela; izan ere, oroimen-proban denbora gehiago behar dute, akats gehiago egiten dituzte eta ez dute bilaketa-estrategiarik garatzen. Maila mikroskopikoan, hipokanpoko CA1 eskualdean, CB1 hartzaile askoz gutxiago aurkezten dituzte eta astrozitoen hiperplasia eta hipertrofia agertzen dituzte. Emaitzek erakusten dute LLEk oroimen-espazialean eragin kaltegarriak dituela eta, beraz, aztertu daitekeen ezaugarri bat dela LLEk eragindako kalteak detektatzeko. Bestalde, CA1 eskualdean astrozitoen eta CB1 hartzaileen aldaketak sortzen ditu, eta baliteke horiek oroimen-urritasunaren eta krisi epileptikoen larritasun mailarekin erlazionatuta egotea. Euskara[EN] Temporal lobe epilepsy (TLE) is a type of partial epilepsy which is often resistant to anti-epileptic drugs. In TLE, unconventional neuronal activity takes place, in the hippocampus among other brain areas. TLE patients frequently show memory disorders and they are more likely to suffer from depression. Moreover, they usually present alterations in the endocannabinoid (eCB) system as well as astrocytic hypertrophy and hyperplasia. A TLE animal model was used to examine hippocampal dependant behaviours such as anxiety, spatial memory and nesting, and hippocampal changes in the expression of CB1 receptors and astrocytes. Three animal groups were compared: controls and animals which have suffered mild and severe epileptic seizures. In the three groups behavioral tests were conducted to analyse the degree of anxiety, spatial memory and their nests. Lastly, immunocitochemistry procedures were performed to study the hippocampus at light microscopy. We saw that animals who have suffered severe epileptic seizures have spatial memory impairment as they need more time in the memory test, they make more mistakes and they do not develop any strategy. At microscopic level, in the CA1 hippocampus region there is lower expression of CB1 receptors and there are astrocytic hypertrophy and hyperplasia. These results demonstrate that TLE impairs spatial memory, thus, it is an analysable feature that can be used to detect the damages caused by TLE. Furthermore, TLE causes changes in the CB1 receptors and astrocytes from the CA1 region and those alterations might be related to the memory impairment and the severity of the seizures. Ingelera[ES] La epilepsia (LLE) del lóbulo local es un tipo de epilepsia parcial que muchas veces es intratable con medicamentos anti epilepsia. En LLE la actividad neuronal no convencional tiene lugar, entre otras cosas, en el hipocampo. En los pacientes con LLE se han detectado problemas de memoria y alta probabilidad de sufrir depresión. Además presentan cambios en el sistema endocannabinoide (eKB) e incluyen hipertrofia e hiperplasia de los astrocitos. En este trabajo se analiza en un modelo animal de la LLE la ansiedad, la memoria y la capacidad de nidificación, dependientes del hipocampo, así como los cambios en la expresión y en los astrocitos de los receptores CB1 que se producen en el hipocampo. Hemos comparado tres grupos de animales que han sufrido controles y ataques de epilepsia leves y graves. Con los tres se han realizado pruebas de comportamiento para analizar el grado de ansiedad y la memoria espacial y analizar sus nidos. Finalmente, se han llevado a cabo procedimientos inmunohistoquímicos para el estudio del hipocampo animal mediante microscopía de luz. Hemos visto que los animales que han sufrido graves crisis epilépticas tienen dañada la memoria espacial, ya que necesitan más tiempo en la prueba de memoria, cometen más errores y no desarrollan estrategias de búsqueda. A nivel microscópico, en la región hipocampo CA1 presentan muchos menos receptores CB1 y presentan hiperplasia e hipertrofia de los astrocitos. Los resultados muestran que la LLE tiene efectos nocivos sobre la memoria espacial y que, por tanto, es una característica analizable para detectar los daños producidos por la LLE. Por otra parte, en la región CA1 se producen cambios en los astrocitos y receptores CB1 que pueden estar relacionados con el grado de inmemoria y la gravedad de las crisis epilépticas

Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease.

The alteration of the endocannabinoid tone usually associates with changes in the expression and/or function of the cannabinoid CB1 receptor. In Alzheimer's disease (AD), amyloid beta (Aβ)-containing aggregates induce a chronic inflammatory response leading to reactivity of both microglia and astrocytes. However, how this glial response impacts on the glial CB1 receptor expression in the subiculum of a mouse model of AD, a brain region particularly affected by large accumulation of plaques and concomitant subcellular changes in microglia and astrocytes, is unknown. The CB1 receptor localization in both glial cells was investigated in the subiculum of male 5xFAD/CB2EGFP/f/f (AD model) and CB2EGFP/f/f mice by immuno-electron microscopy. The findings revealed that glial CB1 receptors suffer remarkable changes in the AD mouse. Thus, CB1 receptor expression increases in reactive microglia in 5xFAD/CB2EGFP/f/f, but remains constant in astrocytes with CB1 receptor labeling rising proportionally to the perimeter of the reactive astrocytes. Not least, the CB1 receptor localization in microglial processes in the subiculum of controls and closely surrounding amyloid plaques and dystrophic neurites of the AD model, supports previous suggestions of the presence of the CB1 receptor in microglia. These findings on the correlation between glial reactivity and the CB1 receptor expression in microglial cells and astrocytes, contribute to the understanding of the role of the endocannabinoid system in the pathophysiology of Alzheimer's disease.post-print4763 K

Ingurune aberastuak nerabezaroko gehiegizko alkohol kontsumoaren ondoriozko portaera kalteak berreskuratzen ditu C57BL/6J sagu helduetan

The use and abuse of alcohol (EtOH) is one of the world’s main health issues that strikingly impacts on our society, as heavy episodic drinking is becoming more and more common in the adolescence when the brain is particularly vulnerable to EtOH. However, molecular, anatomical, functional and behavioral alterations improve inyoung adult mice brains by an enriched environment (EE) exposure after adolescence EtOH consumption [21]. It remains unknown whether these beneficial effects are maintained over a long period of time after cessation of EtOH consumption. The aim of this study was to measure the long-term behavioral consequences of EtOH consumption and to explore the effects of EE in adulthood. For this goal, we treated C57BL/6J male mice with 20% EtOH or water during the 4 weeks of adolescence (p32-p56) followed by an abstinence period (p56-p90). Finally, they were exposed to EE for two weeks (p90-p104) and behavioral tests were conducted at their full adulthood: thigmotaxis for anxiety-like behaviour; novel object recognition test (NORT) for object recognition memory; novel object location test (NOLT) for location memory and beam walking balance test (BWBT) for motor coordination and balance. Object and spatial recognition memory were significantly lower in EtOH-treated mice. Also, motor coordination and balance were impaired after EtOH intake. Noticeably, memory and motor deficits reversed to control values after EE. In conclusion, we show that EE recovers the long-term behavioral and motor deficits after abusive EtOH consumption during adolescence. These results point to the beneficial effects EE have in EtOH addiction.; Alkohola (EtOH) munduan gehien kontsumitzen den substantzia psikoaktiboa da eta nerabezaroko alkoholaren kontsumo intentsiboa geroz eta ohikoagoa da. Adin tarte horretan burmuina garatzen ari da eta hainbat garun-atal zaurgarriagoak dira neurotoxikoen kalteen aurrean; hipokanpoa eta garuntxoa, esaterako. Ingurune aberastuak (IAk), aldaketa molekular, anatomiko zein funtzionalak eragiten ditu garunaren garapen prozesuan eta alkoholaren ondorioz helduaro goiztiarreko saguek galdutako portaera gaitasunen berreskurapena sustatzen du. Hala ere, IAk eragindako efektu mesedegarri horiek epe luzerago batean mantentzen diren aztertzeke dago. Ikerketa honen helburuak hurrengoak dira: nerabezaroko gehiegizko alkohol kontsumoak helduaroan eragiten dituen portaera aldaketak ikertzea eta parametro hauetan IAk izan ditzakeen onurak aztertzea. Horretarako, C57BL/6J sagu arrei nerabezaroko 4 astetan zehar (p32-p56) alkohol edo ur tratamendua eman zaie. Ondoren, helduaro goiztiarrean (p56-p90) animaliak abstinentzia egoeran mantendu dira eta helduaroan (p90-p104) saguen kumaldi erdia IAko baldintzetan jarri da 2 astez. Abstinentzia tarte horren azken egunetan portaera probak burutu dira: eremu irekiaren proba, antsietate maila neurtzeko; objektu berrien ezagutze proba, ezagutze oroimenerako; objektuen kokaleku berriaren ezagutze proba, oroimen espazialerako eta oreka proba, oreka eta koordinazio motorrerako. Alkohol taldeko saguek bereizketa indize baxuagoak erakutsi dituzte bai ezagutze oroimen proban baita oroimen espazialean ere, alkohol kontsumoaren ondoriozko narriadura kognitibo adierazgarria iradokiz. Antzeko emaitzak behatu dira oreka proban ere, non alkohol taldeko saguek (EtOH) oreka eta koordinazio motorra kaltetuta erakutsi duten. Interesgarriki, animaliak IAko baldintzapean jartzean objektuak eta kokalekuak bereizteko gaitasuna berreskuratzen dute eta oreka eta koordinazio maila hobetzen dute helduaroan, kontrol taldekoen (H2O) antzeko balioetaraino. IAk alkoholaren ondoriozko helduaroko efektu kaltegarriak leheneratzeko gaitasuna duela erakutsi du

Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery

Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery

Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery