Neuronal cytoskeleton and synaptic densities are altered after a chronic treatment with the cannabinoid receptor agonist WIN 55,212-2

Tagliaferro, Patricia; Ramos, Alberto Javier; Onaivi, Emmanuel S.; Evrard, Sergio Gustavo; Lujilde, Javier; Brusco, Alicia

doi:10.1016/j.brainres.2005.12.089

Cited by 58 publications

(37 citation statements)

References 49 publications

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“…This may be linked to structural changes or remodeling occurring after D 9 -THC exposure in adolescents and is consistent with observations of cytoarchitectural changes occurring with cannabinoid treatment (Tagliaferro et al, 2006) and other reports of altered expression of the structural-related proteins tubulin and actin (Tahir et al, 1992;Wilson et al, 1996). MBP is a major constituent of the myelin sheath that allows fast saltatory conduction of nerve pulses (Vanrobaeys et al, 2005).…”

Section: Protein Expression Profiles In Adolescent Brainssupporting

confidence: 88%

“…Altered expression of both NP25 and tubulin may reflect a modification in the microtubule cytoskeleton. Moreover, the suggested role of NP25 in synapse formation (Depaz and Wilce, 2006) indicates that disrupted NP25 signaling could account for the altered neuronal cytoskeleton and synaptic contacts seen after chronic WIN 55,212-2 treatment (Lawston et al, 2000;Tagliaferro et al, 2006). Decreases in Ras-related protein Rab-1A may also be linked to dysregulation in synaptic function.…”

Section: Protein Expression Profiles In Adolescent Brainsmentioning

confidence: 99%

“…A recent study indicates that cannabinoids desynchronize hippocampal neuronal assemblies and that this may be linked to cannabinoid-induced memory impairment (Robbe et al, 2006). Moreover, hippocampal morphological changes have been observed following chronic administration of cannabinoids (Lawston et al, 2000;Tagliaferro et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Quinn

Matsumoto

Callaghan

et al. 2007

Neuropsychopharmacol

274

226

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The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to D-9-tetrahydrocannabinol (D 9 -THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28 + ) or adult (post-natal day 60 + ) developmental stages. Adult rats avoided a D 9 -THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final D 9 -THC injection. In contrast, adolescent rats showed no significant place aversion. Adult D 9 -THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent D 9 -THC pretreated rats showed decreased social interaction, while only D 9 -THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last D 9 -THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual D 9 -THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent D 9 -THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in D 9 -THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated D 9 -THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.

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Section: Protein Expression Profiles In Adolescent Brainssupporting

confidence: 88%

Section: Protein Expression Profiles In Adolescent Brainsmentioning

confidence: 99%

See 1 more Smart Citation

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Quinn

Matsumoto

Callaghan

et al. 2007

Neuropsychopharmacol

274

226

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“…Morphological changes in the hippocampus have been observed following chronic administration of cannabinoids [117,118]. Two-dimensional gel electrophoresis proteomic analysis conducted on THC-treated hippocampal samples revealed several proteins showing long-lasting alterations in response to THC administration.…”

Section: Neurobiological Mechanisms Underlying Adolescent Cannabinoidmentioning

confidence: 99%

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

Viveros

Marco

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The endocannabinoid (eCB) system, which is involved in the regulation of emotional and motivational homeostasis, synaptic plasticity and cognitive functions, also plays a critical role in diverse phases of brain development. Both perinatal and periadolescent periods are critical for brain eCB system development. Thus, interference of endocannabinoid signalling by cannabis exposure may contribute to explain the enduring negative impact of cannabis on neurodevelopmental processes and the resulting psycho-physio-pathological consequences. In the present chapter we describe and discuss published data dealing with the long-term neurobehavioural effects of cannabis exposure during the prenatal and adolescent periods. Human studies have demonstrated that marijuana consumption by pregnant women critically affects the neurobehavioural development of their children. Investigations using animal models provide useful information for a better understanding of the long-lasting deleterious consequences of cannabis exposure during pregnancy and lactation. Increasing use of cannabis among adolescents is a matter of great public concern that has led to a parallel increase in research on appropriate animal models. Chronic administration of cannabinoid agonists during the periadolescent period causes persistent behavioural alterations related to cognitive deficits, increased risk of psychosis, mood disorders and addiction to cannabis and other drugs of abuse. The underlying mechanisms by which cannabis use may lead to these disorders, including genetic vulnerability and the increasing content of the main psychoactive ingredient in cannabis preparations, delta-9-tetrahydrocannabinol (THC), will be discussed. To conclude, prevention and therapeutic strategies based on scientific knowledge will be proposed.

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“…Quantificação pela técnica de imunohistoquímica (n = 5 (AMERI, 1999;FERNANDÉZ-RUIZ et al, 2000;FRIDE;HOWLETT et al, 2002HOWLETT et al, , 2004PERTWEE, 1997PERTWEE, , 2001). Vários estudos também apontam os canabinóides endógenos como moduladores dos processos ontogenéticos do encéfalo (BEGBIE; DOHERTY; GRAHAM, 2004;FERNANDÉZ-RUIZ et al, 2000;LEONELLI et al, 2005;RAMOS et al, 2002), propriedades neuroprotetoras em diversos modelos de neurotoxicidade (GRUNDY; RABUFFETTI; BELTRAMO, 2001;DEL OLMO;PAZOS, 2003;PARMENTIER-BATTEUR et al, 2002; VAN DER STELT et al, 2002, 2005 e como mediador de processos de plasticidade em diversas estruturas do sistema nervoso central (ALVARES et al, 2006;CHAVES et al, 2008; HASHIMOTODAN; OHNO-SHOSAKU; KANO, 2007;TAGLIAFERRO et al, 2006).…”

Section: 77unclassified

O receptor canabinóide CB1 nos núcleos da base e a sua participação no processo degenerativo em modelos da Doença de Parkinson.

Kirsten¹

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São Paulo 2013Aos meus pais, Dilson e Rosana. Aos meus irmãos, Alexandre e Carolina.Ao meu marido Thiago. AGRADECIMENTOSDurante todo o processo dessa intensa caminhada eu pude contar com o apoio de diversas pessoas. Esse apoio veio de várias formas, como, por exemplo, auxílio nos experimentos, conselhos, conversas formais e informais, orientações intelectuais, ideias, discussões científicas, discussões filosóficas, entre outros. Por isso sei que eu não conseguiria desenvolver este trabalho sem essas preciosas ajudas e por este motivo tenho muitas pessoas a agradecer. O sistema canabinóide parece exercer um papel modulador em vários processos neurobiológicos, incluindo processos de neuroproteção, neurodegeneração e plasticidade neuronal. Os receptores canabinóides to tipo 1 (CB 1 ) são abundantemente expressos nos núcleos da base, porém existem poucos estudos morfológicos detalhados a respeito da localização exata do CB 1 nessa circuitaria. Além disso, este sistema tem sido explorado no contexto da Doença de Parkinson (DP), a segunda doença neurodegenerativa mais comum, e que tem como principal circuitaria afetada os núcleos da base. Dados atuais sobre a modulação do CB 1 em diferentes fases da DP, a relação do sistema canabinóide com outros neurotransmissores, bem como a participação de agentes canabinóides no processo de degeneração ou neuroproteção da DP são bastante controversos. Assim este trabalho teve como objetivos (1) investigar a localização dos receptores CB 1 nos núcleos da base de ratos, (2) avaliar o decurso temporal da expressão dos receptores CB 1 e de marcadores dos sistemas dopaminérgico e GABAérgico em um modelo experimental da DP in vivo e, (3) avaliar os efeitos do tratamento com compostos canabinóides em modelos experimentais da DP in vivo e in vitro. Assim em uma primeira etapa investigamos nos núcleos da base (estriado, substância negra -SN, globo pálido externo -GPe e globo pálido interno -GPi) de ratos intactos, o padrão de distribuição do receptor CB 1 com marcadores de células da glia (astrócitos, microglia e oligodendrócito), de elementos estruturais neurônios (axônios e dendritos), de neurônios dopaminérgicos (TH-tirosina hidroxilase) e de neurônios GABAérgicos (proteínas ligantes de cálcio parvalbumina e calbindina), através de estudos de dupla-marcação com imunofluorescência. Avaliamos o decurso temporal da expressão de CB 1, TH, GABA, GAD (descarboxilase do ácido glutâmico), calbindina e parvalbumina nos núcleos da base, por imunohistoquímica e/ou immunoblotting, em ratos submetidos à injeção unilateral intraestriatal de 6-OHDA (modelo de DP in vivo). Neste mesmo modelo investigamos as alterações comportamentais motoras e histológicas após o tratamento com ACEA (agonista do receptor CB 1 ) e com AM 251 (antagonista do receptor CB 1 ). E por fim, avaliamos a viabilidade celular após o tratamento com ACEA, AM 251, AM 404 (inibidor da recaptação de anandamida -canabinóide endógeno) e canabidiol em uma linhagem de neuroblastoma (neuro-2a) diferenciada em neurônios dopaminérgicos e exp...

show abstract

Neuronal cytoskeleton and synaptic densities are altered after a chronic treatment with the cannabinoid receptor agonist WIN 55,212-2

Cited by 58 publications

References 49 publications

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

O receptor canabinóide CB1 nos núcleos da base e a sua participação no processo degenerativo em modelos da Doença de Parkinson.

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