scholarly journals Trigeminal Neuralgia Induced by Cobra Venom Leads to Cognitive Deficits Associated with Downregulation of CREB/BDNF Pathway

2017 ◽  
Vol 2 (20;2) ◽  
pp. 53-67
Author(s):  
Jianxiong An
Keyword(s):  
Cognitive Impairment ◽  
Trigeminal Neuralgia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Memory Deficits ◽  
Cobra Venom ◽  
Spatial Learning And Memory ◽  
Bdnf Pathway

Background: Chronic pain often results in cognitive impairment. Our previous study showed that trigeminal neuralgia induced by cobra venom leads to spatial learning and memory deficits, although the underlying mechanism remains unclear. However, recent evidence indicates that the c-AMP-responsive element binding protein (CREB)/brain derived neurotrophic factor (BDNF) pathway plays a critical role in various etiologies of cognitive deficits. Objectives: Our aim was to explore the CREB/BDNF pathway to determine the molecular mechanisms involved in the pathogenesis of cognitive impairment caused by cobra venominduced trigeminal neuralgia. Study Design: A randomized, controlled animal study. Setting: Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University. Methods: Fifty male Sprague–Dawley rats were randomly divided into 3 groups: cobra venom group, sham group, and control group. Cobra venom or saline was injected into the sheath of the infraorbital nerve (ION), respectively. Video recordings and mechanical thresholds were used to analyze changes in behavioral activity 3 days before surgery and 4, 7, 14, 21, 28, and 56 days after surgery. Morris water maze tests were conducted at 4- and 8-week time points after surgery to evaluate spatial learning and memory. We also investigated expression changes of phosphorylated CREB (p-CREB) and BDNF in the hippocampus and prefrontal cortex (PFC) using western blotting and immunohistochemistry. Results: Cobra venom-treated rats exhibited significant changes in face grooming, as well as exploratory and resting behaviors, compared with the control group and sham group (both P < 0.001). Rats in the cobra venom group exhibited slightly impaired acquisition (P < 0.05) without memory deficits (P > 0.05) in the first water maze protocol. In the second water maze test, rats in the cobra venom group exhibited spatial learning and memory deficits, with fewer platform site crossings during the probe trial (P < 0.05). Moreover, results showed decreased p-CREB and BDNF expressions in the hippocampus and PFC in the cobra venom group, with significant differences at 9 weeks post-surgery (P < 0.05). Limitations: No signaling inhibitor or genetic manipulation was administered to further confirm upstream factors of the CREB/BDNF pathway in cognitive deficits caused by chronic trigeminal neuralgia. Conclusions: The findings suggest that cognitive impairment caused by cobra venom-induced trigeminal neuralgia is associated with downregulation of the CREB/BDNF pathway in the hippocampus and PFC. Key words: Cognitive impairment, the CREB/BDNF pathway, cobra venom, trigeminal neuralgia, hippocampus, prefrontal cortex, free behavior, Morris water maze

scholarly journals Trigeminal Neuralgia Induced by Cobra Venom in the Rat Leads to Deficits in Abilities of Spatial Learning and Memory

2015 ◽  
Vol 2;18 (2;3) ◽  
pp. E207-E216
Author(s):  
Jian-xiong An
Keyword(s):  
Chronic Pain ◽  
Trigeminal Neuralgia ◽  
Learning And Memory ◽  
Medulla Oblongata ◽  
Spatial Learning ◽  
Water Maze ◽  
Cobra Venom ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Memory Deterioration

Background: Patients with chronic pain usually suffer from cognitive impairment, with memory deterioration being the most common deficit that affects daily functioning and quality of life. The causes for this impairment are not clear despite intensive clinical studies. Few studies have evaluated impaired learning using animal models of persistent pain. Objective: In this study, a new trigeminal neuralgia model induced by cobra venom was adopted to explore effects of chronic pain on spatial learning and memory in rats. Study Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. Methods: Thirty adult male Sprague-Dawley rats were randomly divided into 2 groups (n = 15): NS control group and cobra venom group, 0.9% sterile saline or cobra venom solution was injected into the sheath of the infraorbital nerve (ION), respectively. The development of trigeminal neuralgia was accessed by changes in free behavioral activity 3 days before the surgery and 3, 7, 12, 20, and 30 days after the surgery to identify whether the model was successful or not. Morris water maze test determined the abilities of spatial learning and memory at the time points before the surgery, and 2 weeks and 5 weeks after the surgery. We also observed the ultrastructure of the ION and medulla oblongata of rats following 8 weeks of chronic trigeminal neuropathic pain. Results: Rats with the cobra venom injection displayed significantly more face grooming and fewer exploratory activities compared to the NS control group or baseline (P < 0.01). Both groups improved their latency to reach the platform with the largest difference on the first day (P < 0.01), but without memory deficits in a probe trial for the second water maze protocol. For the third water maze testing, the rats in the cobra venom group experienced decreased abilities of spatial learning and memory, a longer latency with spatial memory deficits during the probe trial (P < 0.05). At the ultrastructural level, we found changes in the medulla oblongata after cobra venom injection resulting in severe demyelination and loss of axons that might be implicated in the causes of cognitive deficits. Limitations: Limitations include partial vision loss in the eye on the lesion side of the rats that might be missed and the absence of evaluating the ultrastructural changes in other parts of the brain. Conclusions: The results of this study suggest that trigeminal neuralgia induced by cobra venom in adult rats can impair spatial learning and memory function over time and results in demonstrable changes in the ultrastructure of the medulla oblongata. This new animal model may be useful for future studies on the effect of chronic pain on learning and cognition. Key words: Cognitive deficits, memory deterioration, cobra venom, trigeminal neuralgia, electron microscopy

Enriched Environment Ameliorates Cognitive Deficits and Locomotor Sensitization in Morphine-Withdrawn Rats Receiving Methadone Maintenance Treatment

2020 ◽  
Vol 79 (6) ◽  
pp. 437-444 ◽  
Author(s):  
Parastoo Akbari ◽  
Mahmoud Najafi ◽  
Ali-Mohammad Rezaei ◽  
Hossein Miladi-Gorji
Keyword(s):  
Object Recognition ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Methadone Maintenance Treatment ◽  
Water Maze ◽  
Maintenance Treatment ◽  
Methadone Maintenance ◽  
Memory Deficits ◽  
Spatial Learning And Memory ◽  
Locomotor Sensitization

<b><i>Objective:</i></b> This study was designed to examine whether enriched environments (EE) would attenuate object recognition and spatial learning and memory deficits and locomotor sensitization induced by methadone maintenance treatment (MMT) in morphine-withdrawn rats. <b><i>Methods:</i></b> Male Wistar rats (170 ± 10 g) were injected with bi-daily doses (10 mg/kg, 12-h intervals) of morphine for 14 days. Rats receiving MMT were reared in the standard environment (SE) or EE during 30 days of morphine withdrawal. Then, the rats were tested for object recognition (the object recognition memory test, ORMT) and spatial learning and memory (the water maze) and then challenged with morphine (1 mg/kg, i.p.) and evaluated for locomotor activity (open-field box). <b><i>Results:</i></b> The results revealed that the dependent/saline/EE (D/Sal/EE) and D/methadone/EE (D/Meth/EE) rats exhibited significant preference for the new object (<i>p</i> = 0.006 and <i>p</i> = 0.049), spent more time in the target zone (<i>p</i> = 0.045 and <i>p</i> = 0.005) on the water maze, and displayed a lower level of distance traveled (<i>p</i> = 0.002 and <i>p</i> = 0.0001) compared to their control groups reared in SE. <b><i>Conclusions:</i></b> We conclude that exposure to EE could ameliorate the object recognition and spatial memory deficits and also decrease locomotor sensitivity in morphine-withdrawn rats receiving MMT. Thus, EE may be beneficial in the treatment of addiction during MMT.

scholarly journals Effects of Chronic Administration of Pioglitazone on Learning and Memory in Rat Model of Streptozotocin-induced Alzheimer’s Disease

2020 ◽  
Vol 24 (4) ◽  
pp. 294-307
Author(s):  
Ehsan Aali ◽  
◽  
Mohammad Hossein Esmaeili ◽  
Sead Shima Mahmodi ◽  
Poriea Solimani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Rat Model ◽  
Escape Latency ◽  
Chronic Administration ◽  
Spatial Learning And Memory ◽  
Swimming Time

Background: Alzheimer’s Disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. Peroxisome Proliferator-Activated Receptor-γ (PPARγ) play a crucial role in regulating insulin sensitivity and may serve as potential therapeutic targets for AD. Pioglitazone (PIOG), as a PPARγ agonist, reduces β-amyloid and tau proteins, and inhibits neuroinflammation. Objective: This study aims to evaluate the effects of PIOG chronic administration on learning and memory in rat model of Streptozotocin (STZ)-induced AD Methods: Forty-two male Wistar rats were divided into two groups: A. Normal rats divided into three subgroups of Control, Dimethyl Sulfoxide (DMSO), and PIOG; and B. AD rats divided into four subgroups of Vehicle, STZ, STZ+DMSO and STZ+PIOG. The last two AD subgroups received 0.2 mL DMSO and PIOG (10 mg/kg per day) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl per injection site) were administered into lateral ventricles. All rates were trained under the Morris water maze task. Findings: PIOG impaired the spatial learning and memory in normal rats. Intracerebroventricular injection of STZ significantly increased escape latency and swimming time to find the hidden platform compared to the control group (P<0.05). The amnesic effect of STZ was prevented by PIOG administration such that the escape latency and swimming time to find the hidden platform in the STZ+PIOG group were significantly lower than in the STZ+DMSO group (P<0.05). Conversely, the percentage of time spent and distance swimming in the target quadrant in the probe test in the STZ+ PIOG group rats were significantly higher than those in the STZ + DMSO group. Conclusion: PIOG administration impaired spatial learning and memory in normal rats, but improved learning and memory in rats with STZ-induced AD. It can be useful for treatment of cognitive impairment in AD patients.

A cAMP analog attenuates beta-amyloid (1–42)-induced mitochondrial dysfunction and spatial learning and memory deficits

2018 ◽  
Vol 140 ◽  
pp. 34-42 ◽  
Author(s):  
Mehdi Aghsami ◽  
Mohammad Sharifzadeh ◽  
Mohammad Reza Sepand ◽  
Meysam Yazdankhah ◽  
Seyed Afshin Seyednejad ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Beta Amyloid ◽  
Memory Deficits ◽  
Spatial Learning And Memory ◽  
Camp Analog ◽  
Learning And Memory Deficits

scholarly journals Tripchlorolide May Improve Spatial Cognition Dysfunction and Synaptic Plasticity after Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhao-Hui Yao ◽  
Xiao-li Yao ◽  
Shao-feng Zhang ◽  
Ji-chang Hu ◽  
Yong Zhang
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Synaptic Proteins ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Pathophysiological Mechanism

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

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