Role of hypothalamic cannabinoid receptors in post-stroke depression in rats

Wang, Shanshan; Sun, Hong; Liu, Sainan; Wang, Ting; Guan, Jin-Qun; Jia, Jianjun

doi:10.1016/j.brainresbull.2016.01.006

Cited by 23 publications

(14 citation statements)

References 36 publications

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“…CUMS and PSD application in the present study did not modify the rats' activity in the OFT, which corroborates studies reporting unchanged motor activity after exposure of male rodents to CUMS and PSD. [30][31][32] As expected, the FST showed an immobility time-decreasing effect in PSD rats after BDNF-HA2TAT/AAV intranasal delivery, an indicator of anti-depressive behavior.…”

Section: Discussionsupporting

confidence: 73%

<p>A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression</p>

Chen¹,

Dong²,

Liu³

et al. 2020

NDT

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Post-stroke depression (PSD) is one of the most frequent neuropsychiatric disorders associated with stroke characterized by depression. The neuroplasticity hypothesis postulates that loss of brain-derived neurotrophic factor (BDNF) plays a major role in pathophysiology of PSD, and restoration of it may represent a critical mechanism underlying antidepressant efficacy. Methods: In previous studies, we designed a new fusion gene, HA2TAT-BDNF, and cloned it into adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for the delivery of BDNF to central nervous system (CNS) via nose-brain pathway. In this study, we used it to explore the antidepressant effects on PSD rats through behavioral and various histological methods, and try to find out its specific mechanism. Results: Compared with the control group, the PSD+AAV group showed decreased sucrose consumption percentage in the sucrose preference test (SPT) (P < 0.001) and prolonged immobility in the forced swimming test (FST) (P=0.000). However, the nasal administration of BDNF-HA2TAT/AAV reversed results of these two behavioral tests (P>0.05, P >0.05), showing an adequate antidepressant effect. Compared with the control group, the concentrations of BDNF mRNA and protein in the hippocampus (P< 0.05, P < 0.01) and prefrontal cortex (P < 0.01, P < 0.01) of PSD rats both decreased. Increased BDNF mRNA and protein expression was observed in the prefrontal cortex (P > 0.05, P < 0.05), without notable change in the hippocampus (P < 0.05, P < 0.001) of PSD+BDNF rats. Conclusion: These results suggest that BDNF reductions in the prefrontal cortex and hippocampus are associated with the development of post-stroke depression, and that increased levels of BDNF in the prefrontal cortex could be used as a therapeutic target to treat PSD. However, the exact mechanism of BDNF action remains unclear in this regard, hindering the wider application of our method. We expect that our research could facilitate the exploration of pathogenesis and the new treatment method of PSD.

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Section: Discussionsupporting

confidence: 73%

<p>A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression</p>

Chen¹,

Dong²,

Liu³

et al. 2020

NDT

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“…Rats were individually housed in plastic cages at 24°C in a 12-hour light-dark cycle with food and water available ad libitum. Chronic unpredictable mild stress (CUMS) 26 was arranged for 5 consecutive weeks with one or two stressors each day after 1 week of recovery from surgery. Stressors included food deprivation (24 hours), water deprivation (12 hours), 45° cage tilt, overnight illumination (36 hours), swimming in 4°C water (5 minutes), and tail clamping (1 minutes).…”

Section: Poststroke Depression Modelmentioning

confidence: 99%

Morinda officinalis oligosaccharides ameliorate depressive‐like behaviors in poststroke rats through upregulating GLUT3 to improve synaptic activity

Zhu

Peng

et al. 2020

FASEB j.

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Poststroke depression (PSD) is one of the most common psychiatric diseases afflicting stroke survivors, yet the underlying mechanism is poorly understood. The pathophysiology of PSD is presumably multifactorial, involving ischemia‐induced disturbance in the context of psychosocial distress. The homeostasis of glucose metabolism is crucial to neural activity. In this study, we showed that glucose consumption was decreased in the medial prefrontal cortex (mPFC) of PSD rats. The suppressed glucose metabolism was due to decreased glucose transporter‐3 (GLUT3) expression, the most abundant and specific glucose transporter of neurons. We also found Morinda officinalis oligosaccharides (MOOs), approved as an antidepressive Chinese medicine, through upregulating GLUT3 expression in the mPFC, improved glucose metabolism, and enhanced synaptic activity, which ultimately ameliorated depressive‐like behavior in PSD rats. We further confirmed the mechanism that MOOs induce GLUT3 expression via the PKA/pCREB pathway in PSD rats. Our work showed that MOOs treatment is capable of restoring GLUT3 level to improve depressive‐like behaviors in PSD rats. We also propose GLUT3 as a potential therapeutic target for PSD and emphasize the importance of metabolism disturbance in PSD pathology.

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“…In the brain, there are two well-characterized cannabinoid receptors subtypes: cannabinoid type-1 receptors (CB1R; found on presynaptic neurons and densely expressed in the prefrontal cortex and in the hippocampus (Eggan and Lewis, 2007; Tsou et al, 1999)) and cannabinoid type-2 receptors (CB2R; highly-expressed in the peripheral tissues of the immune system, nervous system, and gastrointestinal system (Munro et al, 1993; Navarrete et al, 2013;Wright et al, 2005)). Although CB2R are also found in brain regions such as the prefrontal cortex, hippocampus and hypothalamus (reviewed in Demuth and Molleman, 2006; den Boon et al, 2012; Kim and Li, 2015; Onaivi et al, 2008; Wang et al, 2016), they are not thought to be involved in psychoactive effects of cannabis or SCBs (reviewed in Pertwee, 2006; Reggio, 2010; Caballero and Tseng, 2012). Therefore, this review will focus primarily on the role of CB1R in pro-psychotic effects of marijuana and SCBs.…”

Section: Introductionmentioning

confidence: 99%

Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems

Fantegrossi

Wilson

Berquist

2018

Drug Metabolism Reviews

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An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia. The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis. Identification of molecular mechanisms underlying the pro-psychotic effects of SCB drugs of abuse may establish certain classes of these substances as particularly dangerous, guiding regulations to control availability of these drugs. Likewise, an understanding of the pharmacological interactions which lead to schizophrenia and psychosis subsequent to SCB exposure might guide the development of novel therapies to treat afflicted users.

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Role of hypothalamic cannabinoid receptors in post-stroke depression in rats

Cited by 23 publications

References 36 publications

<p>A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression</p>

<p>A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression</p>

Morinda officinalis oligosaccharides ameliorate depressive‐like behaviors in poststroke rats through upregulating GLUT3 to improve synaptic activity

Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems

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