scholarly journals Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy

2013 ◽  
Vol 203 (3) ◽  
pp. 172-178 ◽  
Author(s):  
Kee-Hong Choi ◽  
Til Wykes ◽  
Matthew M. Kurtz
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Deficits ◽  
Effect Size ◽  
Negative Symptoms ◽  
Verbal Learning ◽  
Spatial Learning And Memory ◽  
Positive Symptoms ◽  
Small Effect Size ◽  
Moderate Effect

BackgroundA growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results.AimsTo investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects.MethodA total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified.ResultsMedications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d = 0.23, P = 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d = 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d = 0.54 and d = 0.62 respectively), and small effect-size improvements on general symptoms (d = 0.46 and d = 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d = 0.33).ConclusionsCholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms.

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 GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

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