scholarly journals Cannabinoids in Audiogenic Seizures: From Neuronal Networks to Future Perspectives for Epilepsy Treatment

2021 ◽  
Vol 15 ◽  
Author(s):  
Willian Lazarini-Lopes ◽  
Raquel A. Do Val-da Silva ◽  
Rui M. P. da Silva-Júnior ◽  
Alexandra O. S. Cunha ◽  
Norberto Garcia-Cairasco

Cannabinoids and Cannabis-derived compounds have been receiving especial attention in the epilepsy research scenario. Pharmacological modulation of endocannabinoid system's components, like cannabinoid type 1 receptors (CB1R) and their bindings, are associated with seizures in preclinical models. CB1R expression and functionality were altered in humans and preclinical models of seizures. Additionally, Cannabis-derived compounds, like cannabidiol (CBD), present anticonvulsant activity in humans and in a great variety of animal models. Audiogenic seizures (AS) are induced in genetically susceptible animals by high-intensity sound stimulation. Audiogenic strains, like the Genetically Epilepsy Prone Rats, Wistar Audiogenic Rats, and Krushinsky-Molodkina, are useful tools to study epilepsy. In audiogenic susceptible animals, acute acoustic stimulation induces brainstem-dependent wild running and tonic-clonic seizures. However, during the chronic protocol of AS, the audiogenic kindling (AuK), limbic and cortical structures are recruited, and the initially brainstem-dependent seizures give rise to limbic seizures. The present study reviewed the effects of pharmacological modulation of the endocannabinoid system in audiogenic seizure susceptibility and expression. The effects of Cannabis-derived compounds in audiogenic seizures were also reviewed, with especial attention to CBD. CB1R activation, as well Cannabis-derived compounds, induced anticonvulsant effects against audiogenic seizures, but the effects of cannabinoids modulation and Cannabis-derived compounds still need to be verified in chronic audiogenic seizures. The effects of cannabinoids and Cannabis-derived compounds should be further investigated not only in audiogenic seizures, but also in epilepsy related comorbidities present in audiogenic strains, like anxiety, and depression.

2020 ◽  
pp. 026988112096593
Author(s):  
Mohaddeseh Ebrahimi-Ghiri ◽  
Fatemeh Khakpai ◽  
Mohammad-Reza Zarrindast

Background: Methamphetamine is an addictive stimulant that possesses toxicity in the brain when taken repeatedly or at higher doses. Methamphetamine neurotoxicity is associated with numerous forms of mental impairment, including depression and anxiety. Evidence has also demonstrated that the endocannabinoid system is involved in the regulation of anxiety and depression. Aims: This study was designed to determine the involvement of the endocannabinoid system in anxiety- and depression-related behaviors in methamphetamine-withdrawal male NMRI mice. Methods: The elevated plus maze and forced swim test were used to assess the level of anxiety and depression. Results: We found that methamphetamine (30 mg/kg, intraperitoneal) evoked depressive- and anxiogenic-like effects at 3 days post-administration. Injection of URB597 (5–10 ng/mouse, intracerebroventricular), 10 min before the test, prevented the emotional deficits induced by methamphetamine withdrawal. Moreover, the cannabinoid receptor type 1 antagonist AM251 (1 μg/mouse) or cannabinoid receptor type 2 antagonist AM630 (5 and 10 μg/mouse) suppressed the antidepressant activity in the methamphetamine-withdrawal mice treated with URB597. The transient receptor potential vanilloid 1 antagonist capsazepine (25 μg/mouse) prevented while capsazepine (100 μg/mouse) potentiated the antidepressant efficacy in the methamphetamine-withdrawal mice treated with URB597. The higher dose of AM630 and two higher doses of capsazepine had antidepressant efficacy, by themselves. Furthermore, capsazepine (50 μg/mouse) increased locomotion in the methamphetamine-withdrawal mice treated with URB597. Conclusions: The results suggest that URB597 has a potential for preventing methamphetamine withdrawal-evoked anxiety and depression. Cannabinoid type 1 receptors, cannabinoid type 2 receptors and transient receptor potential vanilloid 1 differently affect depression-related behaviors in methamphetamine-withdrawal mice treated with URB597.


2021 ◽  
pp. 135910452110261
Author(s):  
Rebecca Hall ◽  
Leanna Keeble ◽  
Sandra-Ilona Sünram-Lea ◽  
Michelle To

Research suggests that as many as 60% of people with type 1 diabetes (T1D) admit to misusing insulin. Insulin omission (IO) for the purpose of weight loss, often referred to as diabulimia, is a behaviour becoming increasingly recognised, not least since prolonged engagement can lead to serious vascular complications and mortality. Several risk factors appear to be relevant to the development of IO, most notably gender, anxiety and depression and increased weight concerns and body dissatisfaction. Evidence suggests that women, especially young girls, are more likely to omit insulin as a method of weight loss compared to men. Mental health conditions such as anxiety and depression are increasingly prevalent in people with T1D compared to their peers, and appear to contribute to the risk of IO. Increased weight concerns and body dissatisfaction are further prominent risk factors, especially given increases in weight which often occur following diagnosis and the monitoring of weight by diabetes teams. This review presents evidence examining these risk factors which increase the likelihood of a person with T1D engaging in IO and highlights the complications associated with prolongment of the behaviour. Further research looking at the comorbidities of these risk factors, alongside other factors, would provide greater insight into understanding IO in people with T1D.


2021 ◽  
pp. 0271678X2199439
Author(s):  
Cen Yang ◽  
Jingjing Liu ◽  
Jingyi Wang ◽  
Anqi Yin ◽  
Zhenhua Jiang ◽  
...  

There are no effective treatments for stroke. The activation of endogenous protective mechanisms is a promising therapeutic approach, which evokes the intrinsic ability of the brain to protect itself. Accumulated evidence strongly suggests that electroacupuncture (EA) pretreatment induces rapid tolerance to cerebral ischemia. With regard to mechanisms underlying ischemic tolerance induced by EA, many molecules and signaling pathways are involved, such as the endocannabinoid system, although the exact mechanisms have not been fully elucidated. In the current study, we employed mutant mice, neuropharmacology, microdialysis, and virus transfection techniques in a middle cerebral artery occlusion (MCAO) model to explore the cell-specific and brain region-specific mechanisms of EA-induced neuroprotection. EA pretreatment resulted in increased ambient endocannabinoid (eCB) levels and subsequent activation of ischemic penumbral astroglial cannabinoid type 1 receptors (CB1R) which led to moderate upregulation of extracellular glutamate that protected neurons from cerebral ischemic injury. These findings provide a novel cellular mechanism of EA and a potential therapeutic target for ischemic stroke.


2021 ◽  
Vol 15 ◽  
Author(s):  
Alejando Fuerte-Hortigón ◽  
Jaime Gonçalves ◽  
Laura Zeballos ◽  
Rubén Masa ◽  
Ricardo Gómez-Nieto ◽  
...  

The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1110-P
Author(s):  
EMILY MALECHA ◽  
KIMBERLY A. DRISCOLL ◽  
VIRAL SHAH ◽  
JANET K. SNELL-BERGEON ◽  
CRISTY GENO RASMUSSEN

2016 ◽  
Vol 25 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Wolfgang Mastnak

ABSTRACTAntenatal music activities are in the ascendant. Regarding evidence-based research, the article advocates 5 main aims: music therapeutic control of pre- and perinatal stress, anxiety, and depression; music-related mental and physical birth preparation comprising cognitive adjustment, emotional regulation, physical activity, relaxation and pain management, and social inclusion; music-associated bonding and self-efficacy; prenatal sound stimulation to trigger learning processes, pedagogical priming and brain maturation; music activities to facilitate the child’s acculturation and adaptive self-regulation. Underlying mechanisms such as neuroplasticity help to understand the multifaceted effects of music in pre- and perinatal care. Individual conditions and features of the mother and her child have to be taken into account and music interventions to be harmonized with complementary perinatal programs.


2020 ◽  
Vol 21 (3) ◽  
pp. 1072
Author(s):  
Daniela Laricchiuta ◽  
Francesca Balsamo ◽  
Carlo Fabrizio ◽  
Anna Panuccio ◽  
Andrea Termine ◽  
...  

To promote efficient explorative behaviors, subjects adaptively select spatial navigational strategies based on landmarks or a cognitive map. The hippocampus works alone or in conjunction with the dorsal striatum, both representing the neuronal underpinnings of the navigational strategies organized on the basis of different systems of spatial coordinate integration. The high expression of cannabinoid type 1 (CB1) receptors in structures related to spatial learning—such as the hippocampus, dorsal striatum and amygdala—renders the endocannabinoid system a critical target to study the balance between landmark- and cognitive map-based navigational strategies. In the present study, mice treated with the CB1-inverse agonist/antagonist AM251 or vehicle were trained on a Circular Hole Board, a task that could be solved through either navigational strategy. At the end of the behavioral testing, c-Fos immunoreactivity was evaluated in specific nuclei of the hippocampus, dorsal striatum and amygdala. AM251 treatment impaired spatial learning and modified the pattern of the performed navigational strategies as well as the c-Fos immunoreactivity in the hippocampus, dorsal striatum and amygdala. The present findings shed light on the involvement of CB1 receptors as part of the selection system of the navigational strategies implemented to efficiently solve the spatial problem.


2019 ◽  
Vol 33 (5) ◽  
pp. 606-614 ◽  
Author(s):  
Alice Hartmann ◽  
Aline Fassini ◽  
América Scopinho ◽  
Fernando MA Correa ◽  
Francisco S Guimarães ◽  
...  

Background: The dorsal hippocampus has a central role in modulating cardiovascular responses and behavioral adaptation to stress. The dorsal hippocampus also plays a key role in stress-associated mental disorders. The endocannabinoid system is widely expressed in the dorsal hippocampus and modulates defensive behaviors under stressful conditions. The endocannabinoid anandamide activates cannabinoid type 1 receptors and is metabolized by the fatty acid amide hydrolase enzyme. Aims: We sought to verify whether cannabinoid type 1 receptors modulate stress-induced cardiovascular changes, and if pharmacological fatty acid amide hydrolase inhibition in the dorsal hippocampus would prevent the cardiovascular responses and the delayed anxiogenic-like behavior evoked by restraint stress in rats via cannabinoid type 1 receptors. Methods: Independent groups received intra-dorsal-hippocampal injections of N-(piperidin-1yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-hpyrazole-3-carboxamide (AM251; cannabinoid type 1 receptor antagonist/inverse agonist, 10–300 pmol) and/or cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597; fatty acid amide hydrolase inhibitor, 10 pmol) before the restraint stress session. Cardiovascular response during restraint stress or later behavioral parameters were evaluated. Results: Acute restraint stress altered the cardiovascular response, characterized by increased heart rate and mean arterial pressure, as well as decreased tail cutaneous temperature. It also induced a delayed anxiogenic-like effect, evidenced by reduced open arm exploration in the elevated plus maze 24 h after stress. AM251 exacerbated the stress-induced cardiovascular responses after injection into the dorsal hippocampus. In contrast, local injection of URB597 prevented the cardiovascular response and the delayed (24 h) behavioral consequences of restraint stress, effects attenuated by pretreatment with AM251. Conclusion: Our data corroborate previous results indicating that the hippocampal endocannabinoid system modulates the outcome of stress exposure and suggest that this could involve modulation of the cardiovascular response during stress exposure.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Dácil Alvarado-Martel ◽  
M. Ángeles Ruiz Fernández ◽  
Maribel Cuadrado Vigaray ◽  
Armando Carrillo ◽  
Mauro Boronat ◽  
...  

Purpose. To explore the factors involved in adherence to self-care behaviors in patients with type 1 diabetes. Materials and Methods. Patients with type 1 diabetes (age range: 14-71 years) were invited to participate at seven Spanish hospitals. They completed a dossier which recorded sociodemographic and clinical variables and also measured personality variables, emotional state, beliefs, and concerns regarding the illness, by means of questionnaires. Results. A total of 428 patients with type 1 diabetes were included (58% women, age 36 (11.8) years, diabetes duration 18.3 (10.2) years, HbA1c 7.9 +/-1.3%). A total of 60.1% of patients found it difficult to follow the treatment recommendations for the care of their disease. The reasons given were mood (25.2%), lack of motivation (13.4%), work (12%), and economic difficulties (3.8%). Other personal reasons were reported by 5.7%. Motivation, training in diabetes management, importance the patient attributed to the disease, and self-efficacy were the variables that predicted adherence to self-care behaviors, together accounting for 32% of its variance. Anxiety and depression were highly prevalent in this study population (57.1% and 23.1%, respectively) and were associated with lower adherence. Conclusion. In the present study assessing patients with type 1 diabetes, motivation, training in diabetes management, beliefs regarding the disease, and self-efficacy were the main contributors to adherence to self-care behaviors. On the other hand, anxiety and depression were highly prevalent and associated with lower adherence. Thus, supplementing therapeutic education with strategies designed to raise levels of motivation, discussion of beliefs about the disease, and encouragement of self-efficacy might be a useful way to increase patient involvement in self-care.


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