RESUMO
The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.
Assuntos
Endocanabinoides , Transtornos do Sono-Vigília , Humanos , Doenças Neuroinflamatórias , Sistema Nervoso Central , Sono , NeurogliaRESUMO
The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.
Assuntos
Sistema Glinfático , Doenças do Sistema Nervoso , Humanos , Sistema Glinfático/metabolismo , Endocanabinoides/metabolismo , Encéfalo/metabolismo , Sistema Nervoso Central , Doenças do Sistema Nervoso/metabolismoRESUMO
Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents "Using Evidence to Talk About Cannabis" and "State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa.
Assuntos
Cannabis , Alucinógenos , Humanos , Opinião Pública , México , Atitude , Agonistas de Receptores de Canabinoides , PercepçãoRESUMO
Orexins/hypocretins (OX) and melanin-concentrating hormone (MCH) neurons located in the lateral hypothalamus seem to modulate different stages of the sleep-wake cycle. OX are necessary for wakefulness and MCH appears to regulate rapid eye movement sleep (REMS). Likewise, endocannabinoids, the endogenous ligands for cannabinoid receptors 1 and 2 (CB1R, CB2R), also modulate REMS in rats. Moreover, it has been shown that the activation of the CB1R in the lateral hypothalamus of rats excites MCH neurons while inhibiting OX neurons in in vitro preparations. Hence, we assessed the effects of 2-arachidonoylglicerol (2-AG, an endocannabinoid) in the lateral hypothalamus on the sleep-wake cycle of rats. We also utilized the CB1R inverse agonist AM251 to further support the involvement of this receptor, and we performed double immunofluorescence experiments to detect c-Fos, as a marker of neural activation, in OX and in MCH neurons to determine which neurons were activated. Our results indicate that 2-AG increases REMS through CB1R activation, and increases c-Fos expression in MCH neurons. These results suggest that endocannabinoid activation of the CB1R in the lateral hypothalamus, which activates MCH neurons, is one mechanism by which REMS is triggered.
Assuntos
Ácidos Araquidônicos/administração & dosagem , Endocanabinoides/administração & dosagem , Glicerídeos/administração & dosagem , Hormônios Hipotalâmicos/metabolismo , Hipotálamo/efeitos dos fármacos , Melaninas/metabolismo , Neurônios/efeitos dos fármacos , Hormônios Hipofisários/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sono REM/efeitos dos fármacos , Animais , Ácidos Araquidônicos/farmacologia , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Hipotálamo/citologia , Hipotálamo/metabolismo , Masculino , Neurônios/metabolismo , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismoRESUMO
Sleep deprivation (SD) produces numerous deleterious changes in brain cells, including apoptosis. It has been demonstrated that growth hormone (GH) stimulates cell growth and counteracts apoptosis, although this anti-apoptotic effect has not been tested against SD. To determine the protective effect of GH administration on cell proliferation and survival in the dentate gyrus (DG) of the hippocampus after sleep deprivation; we injected Wistar adult rats with a low dose of recombinant human GH (rhGH 5 ng/kg) per seven days and then we gently sleep deprived the animals for 48 consecutive hours. 5-Bromodeoxiuridine (BrdU) was administered to assess cell proliferation after the GH treatment and NeuN was used as marker of cell fate. Our results indicate that GH produced a three fold increase in the number of BrdU positive cells within the DG [Control = 1044 ± 106.38 cells, rhGH = 2952 ± 99.84 cells, P<0.01]. In contrast, 48 h of SD significantly reduced cell proliferation but this effect was antagonized by the GH administration [SD = 540 ± 18.3 cells, rhGH + SD = 1116 ± 84.48 cells, P<0.004]. Paradoxically, SD and GH administration increased cell survival separately but no significantly compared with control animals. However, cell survival was increased in animals treated with rhGH+SD compared to rats injected with saline solution [P<0.04]. Within the survival cells, the percentage of neurons was higher in SD animals [95%] compared with saline group, while this percentage (NeuN positive cells) was increased in animals treated with rhGH+SD [120%] compared with rhGH [25%] alone. Our findings indicate that GH strongly promotes cell proliferation in the adult brain and also protects the hippocampal neuronal precursors against the deleterious effect of prolonged sleep loss.