The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.
Aged ; Aged, 80 and over ; Antiemetics/*adverse effects ; Brain/drug effects/pathology ; Cognition Disorders/*chemically induced/*pathology ; Female ; Gastrointestinal Agents/*adverse effects ; Humans ; Male ; Parkinson Disease, Secondary/*chemically induced/*pathology ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

This study investigated the role of glycogen synthase kinase-3β (GSK-3β) in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride (LiCl, 100 mg/kg) and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-3β was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Morris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflurane anesthesia increased mRNA levels of TNF-α, IL-1β and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiCl, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiCl alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-3β in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-κB p65 (Lys310). In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.
Animals ; Cognition Disorders ; chemically induced ; metabolism ; pathology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; chemically induced ; metabolism ; pathology ; Isoflurane ; adverse effects ; Male ; Neurons ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the influence of repeated seizures and anti-epileptic drug on phosphorylated cAMP response element binding protein (pCREB) in rat model of cognitive impairment, and the effect of Caoguo Zhimu Decoction (CZD) on it.

METHODSOn the basis of epileptic model induced by pentylenetetrazol (PTZ), cognitive impairment model was induced by kindling epilepsy with PTZ everyday, which were then di-vided into the model-1 group, the CZD-1 group, the nimodipine-1 group, and those by injecting large dosage phenytoin sodium were divided into the model-2 group, the CZD-2 group and the nimodipine-2 group. Changes of pCREB protein in rat's hippocampus were detected using immunohistochemistry and Western blotting assay.

RESULTSThe expression of pCREB was higher in the CZD-1 and nimodipine-1 group than in the model group, while it was significantly different in the CZD-2 and nimodipine-2 groups than in the model-2 group.

CONCLUSIONCZD could relieve the cognitive dysfunction in the epileptic model rats induced by everyday PTZ kindling or by dilantin through increasing the pCREB expression.

Animals ; Cognition Disorders ; chemically induced ; prevention & control ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Epilepsy ; chemically induced ; drug therapy ; metabolism ; Hippocampus ; drug effects ; metabolism ; pathology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Phenytoin ; adverse effects ; Phosphorylation ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD).

METHODSMale Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons.

RESULTSThe MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg).

CONCLUSIONR. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

Animals ; Behavior, Animal ; drug effects ; Biomarkers ; metabolism ; Cell Count ; Cognition Disorders ; chemically induced ; drug therapy ; physiopathology ; Hippocampus ; drug effects ; pathology ; Injections, Intraventricular ; Male ; Neurons ; drug effects ; pathology ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rhodiola ; metabolism ; Streptozocin ; administration & dosage ; Swimming ; physiology