RESUMO
In Alzheimer´s disease (AD) there is a reduction in hippocampal neurogenesis that has been associated to cognitive deficits. Previously we showed that Andrographolide (ANDRO), the main bioactive component of Andrographis paniculate, induces proliferation in the hippocampus of the APPswe/PSEN1ΔE9 (APP/PS1) mouse model of AD as assessed by staining with the mitotic marker Ki67. Here, we further characterized the effect of ANDRO on hippocampal neurogenesis in APP/PS1 mice and evaluated the contribution of this process to the cognitive effect of ANDRO. Treatment of 8-month-old APP/PS1 mice with ANDRO for 4 weeks increased proliferation in the dentate gyrus as evaluated by BrdU incorporation. Although ANDRO had no effect on neuronal differentiation of newborn cells, it strongly increased neural progenitors, neuroblasts and newborn immature neurons, cell populations that were decreased in APP/PS1 mice compared to age-matched wild-type mice. ANDRO had no effect on migration or in total dendritic length, arborization and orientation of immature neurons, suggesting no effects on early morphological development of newborn neurons. Finally, ANDRO treatment improved the performance of APP/PS1 mice in the object location memory task. This effect was not completely prevented by co-treatment with the anti-mitotic drug TMZ, suggesting that other effects of ANDRO in addition to the increase in neurogenesis might underlie the observed cognitive improvement. Altogether, our data indicate that in APP/PS1 mice ANDRO stimulates neurogenesis in the hippocampus by inducing proliferation of neural precursor cells and improves spatial memory performance.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Diterpenos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Memória Espacial/efeitos dos fármacos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Animais , Giro Denteado/patologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Camundongos Transgênicos , Células-Tronco Neurais/patologia , Neurônios/patologia , Presenilina-1/genéticaRESUMO
The spontaneous object recognition (SOR) task is one of the most widely used behavioral protocols to assess visual memory in animals. However, only recently was it shown that nonhuman primates also perform well on this task. Here we further characterized this new monkey recognition memory test by assessing the performance of adult marmosets after an acute systemic administration of two putative amnesic agents: the competitive muscarinic acetylcholine receptor antagonist scopolamine (SCP; 0.05 mg/kg) and the noncompetitive N-methyl-d-aspartate glutamate receptor antagonist MK-801 (0.015 mg/kg). We also determined whether the acetylcholinesterase inhibitor donepezil (DNP; 0.50 mg/kg), a clinically-used cognitive enhancer, reverses memory deficits caused by either drug. The subjects had an initial 10 min sample trial where two identical neutral objects could be explored. After a 6 h retention interval, recognition was based on an exploratory preference for a new rather than familiar object during a 10 min test trial. Both SCP and MK-801 impaired the marmosets' performance on the SOR task, as both objects were explored equivalently. Co-administration of 0.50 mg/kg of DNP reversed the SCP- but not the MK-801-induced memory deficit. These results indicate that cholinergic and glutamatergic pathways mediate object recognition memory in the monkey SOR task.
Assuntos
Maleato de Dizocilpina/farmacologia , Teste de Campo Aberto/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Escopolamina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Callithrix/metabolismo , Donepezila/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Haplorrinos/metabolismo , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Antagonistas Muscarínicos/farmacologia , Nootrópicos/farmacologia , Receptores Muscarínicos/metabolismoRESUMO
By observing the processes of (bio)medicalization and pharmacologization of society, this article addresses drugs that have been used by healthy individuals to increase cognitive dimensions such as alertness, memory, and concentration. The use of so-called "smart drugs" or "nootropics" has spread among young people, aided by the internet. The circulation of information about such drugs are analyzed using a Brazilian blog called "Cérebro Turbinado," through publications available for public access between 2015 and 2017. The study adopts theoretical and methodological frameworks of the social sciences, including an anthropological perspective. Documental research was conducted on the internet, specifically with scientific dissemination materials and the material available from the aforementioned blog. The results show that the blog acts as a medium for spreading biomedical knowledge among the lay public and indicates the production of new forms of subjectivity by revealing the meanings attributed to these substances in socialization processes.
Al observar los procesos de (bio)medicalización y farmacologización de la sociedad, este artículo aborda los medicamentos que han sido utilizados por individuos sanos para aumentar sus dimensiones cognitivas, como el estado de alerta, la memoria y la concentración. Las llamadas "drogas inteligentes" o "drogas nootrópicas" se han extendido entre los jóvenes a través de Internet. La circulación de información sobre tales drogas se analiza desde un blog brasileño llamado Cérebro Turbinado, sobre el que se realizó una investigación documental basada en el material publicado en el blog entre 2015 y 2017, de acceso público. La investigación adopta marcos teóricos y metodológicos de las ciencias sociales, junto a una perspectiva antropológica. Los resultados muestran que el blog actúa como un medio para la difusión del conocimiento biomédico entre el público lego y muestra la producción de nuevas formas de subjetividad al revelar los significados que se atribuyen a tales sustancias en los procesos de socialización.
Assuntos
Blogging , Cognição/efeitos dos fármacos , Disseminação de Informação/métodos , Nootrópicos/farmacologia , Anfetaminas/farmacologia , Brasil , Estimulantes do Sistema Nervoso Central/farmacologia , Humanos , Medicalização , Metilfenidato/farmacologia , Modafinila/farmacologiaRESUMO
Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound-Δ9-tetrahydrocannabinol (Δ9-THC)-as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Ansiedade/tratamento farmacológico , Agonistas de Receptores de Canabinoides/química , Cannabis/química , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/química , Esquizofrenia/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Ansiedade/fisiopatologia , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/isolamento & purificação , Monoterpenos Bicíclicos/farmacologia , Canabidiol/química , Canabidiol/isolamento & purificação , Canabidiol/farmacologia , Agonistas de Receptores de Canabinoides/classificação , Agonistas de Receptores de Canabinoides/isolamento & purificação , Agonistas de Receptores de Canabinoides/farmacologia , Disfunção Cognitiva/fisiopatologia , Dronabinol/química , Dronabinol/isolamento & purificação , Dronabinol/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Fármacos Neuroprotetores/classificação , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Nootrópicos/química , Nootrópicos/classificação , Nootrópicos/isolamento & purificação , Nootrópicos/farmacologia , Esquizofrenia/fisiopatologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
Recent clinical and epidemiological observations point to a correlation between disorders of energy metabolism, such as obesity and diabetes, and cognitive decline and dementia. Many studies indicate that these age-related conditions closely interact with each other, but the underlying molecular and physiological mechanisms for such correlations are largely unknown. Insulin and leptin, hormones classically implicated in diabetes and obesity, are gaining increasing attention for their participation in cognitive processes and memory. Disrupted signaling by those hormones is associated with impaired brain function. The current review discusses how restoration of insulin and leptin signaling in the brain may attenuate neuronal damage and promote cognition. We further discuss potential therapeutic approaches involving the use of insulin and leptin as cognitive enhancers in the context of metabolic disorders and Alzheimer's disease. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Insulina/uso terapêutico , Leptina/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/psicologia , Nootrópicos/farmacologia , Animais , Biomarcadores , Metabolismo Energético/efeitos dos fármacos , HumanosRESUMO
Histamine H3 receptors (H3R) have attracted interest of research groups as drug target to several CNS disorders. Data suggests that H3R antagonists exert neuroprotective, cognitive enhancement and antidepressant effects in rodents. The LINS01 compounds were reported as selective H3R antagonists, but their effects on memory, anxiety-like behaviour and spontaneous locomotor activity were not evaluated to date. Therefore, this study employed the plus-maze discriminative avoidance task (PM-DAT) to assess concomitantly the effects of LINS01 compounds on short- and long-term memory, anxiety-like behaviour and spontaneous locomotor activity. Thirty-eight adult male Wistar rats were divided into five groups (nâ¯=â¯7-8 per group) according to the treatment. The animals were treated with donepezil (1â¯mg/kg) and clobenpropit (3â¯mg/kg) (reference compounds), and with two LINS01 compounds at doses of 5â¯mg/kg (LINS01003 and LINS01004), and then submitted to the PM-DAT protocol. Saline (vehicle) was used as control group. The behavioural data showed that anxiety-like behaviour, spontaneous locomotor activity and memory effects (short- and long-term) were not affected by the treatment with LINS01004 or clobenpropit. Conversely, treatment with LINS01003 and donepezil impaired the maintenance of discriminative avoidance long-term memory, a hippocampal-dependent memory. Donepezil-treated rats also showed decreased spontaneous locomotor activity and anxiolytic-like effects. In summary, considering that hippocampal damage and memory impairment are associated with Alzheimer's disease (AD), this work brought important findings regarding the contribution of the histamine system to the effects of LINS01 compounds on memory, anxiety and motility, and suggests that H3R antagonism had no effects on anxiety-like behaviour and do not impair discriminative avoidance memory. Furthermore, the findings herein raise new questions about donepezil's function in an "impaired" system such as AD, since it prevented the long-term memory formation in healthy rats.
Assuntos
Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H3/farmacologia , Locomoção/efeitos dos fármacos , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Animais , Benzofuranos/farmacologia , Donepezila/farmacologia , Imidazóis/farmacologia , Masculino , Piperazinas/farmacologia , Ratos , Ratos Wistar , Tioureia/análogos & derivados , Tioureia/farmacologiaRESUMO
RESUMEN Al observar los procesos de (bio)medicalización y farmacologización de la sociedad, este artículo aborda los medicamentos que han sido utilizados por individuos sanos para aumentar sus dimensiones cognitivas, como el estado de alerta, la memoria y la concentración. Las llamadas "drogas inteligentes" o "drogas nootrópicas" se han extendido entre los jóvenes a través de Internet. La circulación de información sobre tales drogas se analiza desde un blog brasileño llamado Cérebro Turbinado, sobre el que se realizó una investigación documental basada en el material publicado en el blog entre 2015 y 2017, de acceso público. La investigación adopta marcos teóricos y metodológicos de las ciencias sociales, junto a una perspectiva antropológica. Los resultados muestran que el blog actúa como un medio para la difusión del conocimiento biomédico entre el público lego y muestra la producción de nuevas formas de subjetividad al revelar los significados que se atribuyen a tales sustancias en los procesos de socialización.
ABSTRACT By observing the processes of (bio)medicalization and pharmaceuticalization of society, this article addresses drugs that have been used by healthy individuals to increase cognitive dimensions such as alertness, memory, and concentration. The use of so-called "smart drugs" or "nootropics" has spread among young people, aided by the internet. The circulation of information about such drugs are analyzed using a Brazilian blog called "Cérebro Turbinado," through publications available for public access between 2015 and 2017. The study adopts theoretical and methodological frameworks of the social sciences, including an anthropological perspective. Documental research was conducted on the internet, specifically with scientific dissemination materials and the material available from the aforementioned blog. The results show that the blog acts as a medium for spreading biomedical knowledge among the lay public and indicates the production of new forms of subjectivity by revealing the meanings attributed to these substances in socialization processes.
Assuntos
Humanos , Cognição/efeitos dos fármacos , Nootrópicos/farmacologia , Disseminação de Informação/métodos , Blogging , Brasil , Medicalização , Modafinila/farmacologia , Anfetaminas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Metilfenidato/farmacologiaRESUMO
RESUMO. O objetivo deste artigo, de caráter teórico descritivo, foi analisar as principais motivações para o aprimoramento cognitivo farmacológico na contemporaneidade, mediante o diálogo com autores que investigaram alguns fenômenos da denominada pós-modernidade, tais como Deleuze (1992), Foucault (2000), Bauman (2001) e Han (2015), além de autores do campo psicanalítico (Bezerra Júnior, 2010; Ferraz, 2014; Birman, 2014) que tecem críticas à questão da medicalização da educação e seus desdobramentos. Constatou-se que, na atualidade, a busca pelo aprimoramento cognitivo farmacológico está intimamente ligada ao estilo de vida e ao de sociedade construídos nas últimas décadas. Independentemente da palavra utilizada para nomear o momento histórico vivido, está cada vez mais difícil lidar com a realidade e, nesse contexto, o aprimoramento cognitivo farmacológico revela-se como uma das facetas do fenômeno recente conhecido como psiquiatrização da normalidade. Como resultado, nota-se também que o uso não médico e indiscriminado de medicamentos para 'turbinar' o cérebro tem tornado uma prática comum entre os estudantes universitários; por esse motivo, não se trata meramente de uma questão educacional relacionada à interferência nos processos de ensino e de aprendizagem, mas de um problema de saúde pública. Conclui-se que esse fenômeno suscita, na sociedade atual, desafios de diferentes ordens, razão pela qual merece atenção especial da comunidade científica.
RESUMEN. El objetivo de este artículo, de carácter teórico descriptivo, ha sido el de analizar las principales motivaciones para el perfeccionamiento cognitivo farmacológico en la contemporaneidad, el diálogo con autores que investigaron algunos fenómenos de la llamada posmodernidad, tales como Deleuze (1991), Foucault (2000), Bauman (2001) y Han (2015), además de autores del campo psicoanalítico (Bezerra Júnior, 2010; Ferraz, 2014; Birman, 2014) que lanzan críticas a la cuestión de la medicalización de la educación y sus desdoblamientos. Se constató que actualmente, la búsqueda por el perfeccionamiento cognitivo farmacológico está íntimamente conectada al estilo de vida y de la sociedad construido em las últimas décadas. Independientemente de la palabra utilizada para nombrar el momento histórico vivido, está cada día más difícil lidiar con la realidad y, en ese contexto, el perfeccionamiento cognitivo farmacológico se revela cómo a una de las facetas del fenómeno reciente conocido como psiquiatrización de la normalidad. Como resultado, se nota también que el uso no medico e indiscriminado de medicinas para potencializar el cerebro se ha tornado una práctica común entre los estudiantes universitarios; por ese motivo, no se trata meramente de una cuestión educacional relacionada a la interferencia en los procesos de enseñanza y aprendizaje, pero de un problema da salud pública, se concluye que ese fenómeno suscita, en la sociedad actual, desafíos de diferentes órdenes, razón por la cual merece atención especial de la comunidad científica.
ABSTRACT. The aim of this theoretical descriptive study was to analyze the main motivations for pharmacological cognitive enhancement in contemporary times through the dialogue with authors who investigated some phenomena of the so-called post-modernity, such as Deleuze (1992), Foucault (2000), Bauman (2001) and Han (2015), in addition to authors of the psychoanalytic field (Bezerra Júnior, 2010; Ferraz, 2014; Birman, 2014) that criticize the issue of medicalization of education and its consequences. It was found that, currently, the search for pharmacological cognitive enhancement is closely linked to the lifestyle and society built in the last decades. Regardless of the name given to the historical moment the society is, it is increasingly difficult to deal with reality and, in this context, the pharmacological cognitive enhancement is revealed as one of the facets of the recent phenomenon known as 'psychiatrization of normality'. As a result, it is also noted that the non-medical and indiscriminate use of drugs to boost brainpower has become a common practice among college students; for this reason, it is not merely an educational issue that may interfere with the teaching-learning process, but also a public health problem. It is concluded that this phenomenon raises, in today's society, challenges of different orders, which is why it deserves special attention from the scientific community.
Assuntos
Preparações Farmacêuticas , Disfunção Cognitiva/psicologia , Psiquiatria , Estudantes , Saúde Pública , Comportamento Competitivo/efeitos dos fármacos , Nootrópicos/farmacologia , Medicalização , Motivação/efeitos dos fármacosRESUMO
The object discrimination test allows the testing of different memory retention periods. However, few behavioral endpoints have been measured in fish species such that retention is often assessed using a single parameter (time spent in object area). Here, we aimed to explore the object discrimination test in zebrafish by assessing their behavioral performance after 1 or 24 h retention interval periods. To characterize putative interaction-like behaviors, fish were tested in the absence or presence of scopolamine (1 h before test session). Zebrafish were habituated for 3 consecutive days in the experimental tank, and training session was performed for 10 min using two identical nonpreferred objects (black cube or sphere). After the retention intervals, a familiar object was replaced by a novel object (test session, 10 min). Fish were also exposed to the novel tank diving test to assess locomotion and anxiety-like behaviors. At 1 h retention interval, animals performed more circular-like investigation near the familiar object, whereas 24 h after training session, a prominent rapid investigation was observed when animals explore the nonfamiliar object. Because scopolamine abolished these phenotypes, as well as the increased time spent in the novel object area during the test without changing locomotion and anxiety-related parameters, the behavioral responses described here may predictively reflect interaction-like behaviors involved in object discrimination memory in zebrafish models.
Assuntos
Cognição/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Nootrópicos/farmacologia , Reconhecimento Visual de Modelos/efeitos dos fármacos , Escopolamina/farmacologia , Peixe-Zebra/fisiologia , Animais , Transtornos da Memória/induzido quimicamenteRESUMO
OBJECTIVE: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages. METHODS: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined. RESULTS: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions. CONCLUSIONS: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deï¬cits associated with AD in humans.