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Antipsychotics influence Toll-like receptor (TLR) expression and its relationship with cognitive functions in schizophrenia

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BRAIN BEHAVIOR AND IMMUNITY 2017年 62卷 256-264页

作者： Keri, Szabolcs Szabo, Csilla Kelemen, Oguz Budapest Univ Technol & Econ Dept Cognit Sci Egry Str 1 H-1111 Budapest Hungary Nyiro Gyula Hosp Natl Inst Psychiat & Addict Budapest Hungary Univ Szeged Fac Med Dept Physiol Szeged Hungary Univ Szeged Fac Med Dept Behav Sci Szeged Hungary

Increasing evidence suggests that altered immune functions are related to the pathophysiology of schizophrenia. Relatively little information is available on Toll-like receptors (TLRs), which are implicated in the recognition of molecular patterns associated with pathogens and internal cellular damage signals. By using immunophenotyping and flow cytometry, we investigated TLRs in CD14+ monocytes, CD4+CD25 +Foxp3+ regulatory T cells (T-reg), and CD3+CD4+CD25+ activated T cells (T-act) in 35 drug-naive patients with schizophrenia before and after an 8-week period of antipsychotic treatment with risperidone or olanzapine. As compared with 30 healthy control individuals, drug-naive patients with schizophrenia exhibited an increased percentage of TLR4+ and TLR5+ monocytes and TLR5+ T-reg/T-act cells. At the end of the treatment period, we observed normalized TLR4+ monocytes and an up-regulation of TLR2+ monocytes and T-reg/T-act cells. Mean fluorescent intensity values, indicating receptor density, were consistent with these findings. In the drug-naive state, but not after treatment, higher percentages of TLR4+ and TLR5+ monocytes were correlated with more severe cognitive deficits. Positive, negative, and general clinical symptoms were not associated with TLRs. There were no significant differences between patients receiving olanzapine and risperidone. These results indicate that abnormal expression of TLR5 can be detected in the earliest stage of schizophrenia, which is modulated by antipsychotics. Immunological alterations in unmedicated schizophrenia patients may be linked to cognitive deficits. (C) 2016 Elsevier Inc. All rights reserved.

关键词： Schizophrenia Toll-like receptors Monocytes Regulatory T cells cognitive functions

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TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation Anesthetics

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2007年第3期323卷 924-934页

作者： Linden, Anni-Maija Sandu, Cristina Aller, M. Isabel Vekovischeva, Olga Y. Rosenberg, Per H. Wisden, William Korpi, Esa R. Univ Helsinki Inst Biomed Pharmacol FIN-00014 Helsinki Finland Heidelberg Univ Dept Clin Neurobiol Heidelberg Germany Helsinki Univ Hosp Dept Anesthesiol & Intens Care Med Helsinki Finland

The TASK-3 channel is an acid-sensitive two-pore-domain K+ channel, widely expressed in the brain and probably involved in regulating numerous neuronal populations. Here, we characterized the behavioral and pharmacological phenotypes of TASK-3 knockout (KO) mice. Circadian locomotor activity measurements revealed that the nocturnal activity of the TASK-3 KO mice was increased by 38% (P < 0.01) compared with wild-type littermate controls, light phase activity being similar. Although TASK-3 channels are abundant in cerebellar granule cells, the KO mice performed as well as the wild-type mice in walking on a rotating rod or along a 1.2-cm-diameter beam. However, they fell more frequently from a narrower 0.8-cm beam. The KO mice showed impaired working memory in the spontaneous alternation task, with the alternation percentage being 62 +/- 3% for the wild-type mice and 48 +/- 4% (P < 0.05) for the KO mice. Likewise, during training for the Morris water-maze spatial memory task, the KO mice were slower to find the hidden platform, and in the probe trial, the female KO mice visited fewer times the platform quadrant than the male KO and wild-type mice. In pharmacological tests, the TASK-3 KO mice showed reduced sensitivity to the inhalation anesthetic halothane and the cannabinoid receptor agonist WIN55212-2 mesylate [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] but unaltered responses to the alpha 2 adrenoceptor agonist dexmedetomidine, the i. v. anesthetic propofol, the opioid receptor agonist morphine, and the local anesthetic lidocaine. Overall, our results suggest important contributions of TASK-3 channels in the neuronal circuits regulating circadian rhythms, cognitive functions, and mediating specific pharmacological effects.

关键词： .reduced cerebellar wild-type mice Granule KO mice Nocturnal exaggerated cognitive functions alternation mice showed TASK channels two-pore-domain Sensitivity to Inhalation TASK Knockout TASK KO

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Evaluation of the impact of compound C11 a new anticonvulsant candidate on cognitive functions and hippocampal neurogenesis in mouse brain

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NEUROPHARMACOLOGY 2020年第0期163卷 107849-000页

作者： Andres-Mach, Marta Szewczyk, Aleksandra Zagaja, Miroslaw Luszczki, Jarogniew Maj, Maciej Rola, Radoslaw Abram, Michal Kaminski, Krzysztof Inst Rural Hlth Isobolog Anal Lab Jaczewskiego 2 PL-20950 Lublin Poland Med Univ Dept Pathophysiol Jaczewskiego 8 PL-20090 Lublin Poland Med Univ Lublin Dept Biopharm Chodzki 4A PL-20090 Lublin Poland Med Univ Lublin Dept Neurol Surg Jaczewskiego 8 PL-20090 Lublin Poland Jagiellonian Univ Med Coll Fac Pharm Dept Med Chem Medyczna 9 PL-30688 Krakow Poland

Searching for the new and effective anticonvulsants in our previous study we developed a new hybrid compound C-11 derived from 2-(2,5-dioxopyrrolidin-l-y1) propanamide. C11 revealed high efficacy in acute animal seizure models such as the maximal electroshock model (MES), the pentylenetetrazole model (PTZ) and the 6 Hz (6 Hz, 32 mA) seizure model, as well as in the kindling model of epilepsy induced by repeated injection of PTZ in mice. In the aim of further in vivo Cl 1 characterization, in the current studies we evaluated its influence on cognitive functions, neurodegeneration and neurogenesis process in mice after chronical treatment. All experiments were performed on 6 weeks old male C57/BL mice. The following drugs were used: C11, levetiracetam (LEV), ethosuximide (ETS) and lacosamide (LCM). We analyzed proliferation, migration and differentiation of newborn cells as well as neurodegenerative changes in a mouse brain after long-term treatment with aforementioned AEDs. Additionally, we evaluated changes in learning and memory functions in response to chronic C11, LEV, LCM and ETS treatment. C11 as well as LEV and ETS did not disturb the proliferation of newborn cells compared to the control mice, whereas LCM treatment significantly decreased it. Chronic AEDs therapy did not induce significant neurodegenerative changes. Behavioral studies with using Morris Water Maze test did not indicate any disturbances in the spatial learning and memory after C11 as well as LEV and ETS treatment in comparison to the control group except LCM mice where significant dysfunctions in time, distance and direct swim to the platform were observed. Interestingly, results obtained from in vivo MRI spectroscopy showed a statistically significant increase of one of the neurometabolites- N-acetyloaspartate (NAA) for LCM and LEV mice. A new hybrid compound C11 in contrast to LCM has no negative impact on the process of neurogenesis and neurodegeneration in the mouse hippocampus. Furthermore

关键词： Neurogenesis Neurodegeration cognitive functions Antiepileptic drugs

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Child maltreatment, cognitive functions and the mediating role of mental health problems among maltreated children and adolescents in Uganda

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CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH 2021年第1期15卷 1页

作者： Ainamani, Herbert E. Rukundo, Godfrey Z. Nduhukire, Timothy Ndyareba, Eunice Hecker, Tobias Kabale Univ Sch Med Dept Mental Hlth Kabale Uganda Bishop Stuart Univ Dept Psychol Mbarara Uganda Mbarara Univ Sci & Technol Dept Psychiat Mbarara Uganda Kabale Univ Dept Pediat Sch Med Kabale Uganda Kabale Univ Dept Educ Psychol Kabale Uganda Bielefeld Univ Dept Psychol Bielefeld Germany

Background Child maltreatment poses high risks to the mental health and cognitive functioning of children not only in childhood but also in later life. However, it remains unclear whether child maltreatment is directly associated with impaired cognitive functioning or whether this link is mediated by mental health problems. Our study aimed at examining this research question among children and adolescents in Uganda. Methods A sample of 232 school-going children and adolescents with a mean age of 14.03 (SD = 3.25) was assessed on multiple forms of maltreatment using the Maltreatment and Abuse Chronology Exposure-Pediatric Version (pediMACE). Executive functions were assessed by the Tower of London task and working memory by the Corsi Block Tapping task, while mental health problems were assessed using the Child PTSD Symptom Scale for PTSD and the Center for Epidemiological Studies Depression Scale for Children (CES-DC). Results In total, 232 (100%) of the participant reported to have experienced at least one type of maltreatment in their lifetime including emotional, physical, and sexual violence as well as neglect. We found a negative association between child maltreatment and executive functions (beta = - 0.487, p < 0.001) and working memory (beta = - 0.242, p = 0.001). Mental health problems did not mediate this relationship. Conclusions Child maltreatment seems to be related to lower working memory and executive functioning of affected children and adolescents even after controlling for potential cofounders. Our study indicates that child maltreatment the affects children's cognitive functionality beyond health and well-being.

关键词： Child maltreatment cognitive functions Mental health East Africa

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Effects of a Physical Activity Program that Incorporates Exercises Targeting Balance, Strength, and Proprioception on cognitive functions and Physical Performance in Old Adults with Mild cognitive Impairment

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JOURNAL OF ALZHEIMERS DISEASE 2023年第1期96卷 245-260页

作者： Boulares, Ayoub Fabre, Claudine Cherni, Ala Jdidi, Hela Chortane, Sabri Gaied Trompetto, Carlo Puce, Luca Bragazzi, Nicola Luigi Univ La Manouba Higher Inst Sport & Phys Educ Ksar Said Res Lab Sport Performance Hlth & Soc LR23JS01 Manouba Tunisia Univ Littoral Cote dOpale Univ Lille Univ Artois URePSSS Unite Rech Pluridisciplinaire Sport Sante Lille France Univ Jendouba High Inst Sport & Phys Educ Kef Res Unit Sports Sci Hlth & Movement UR22JS01 Jendouba Tunisia Univ Poitiers Fac Sports Sci Lab Move UR 20296 Poitiers France Univ Sousse Fac Med Ibn El Jazzar Lab Cardiocirculatory Resp Metab & Hormonal Adapt Sousse Tunisia Univ Genoa Dept Neurosci Rehabil Ophthalmol Genet Maternal & Genoa Italy Osped Policlin San Martino Ist Ricovero & Cura Carattere Sci IRCCS Genoa Italy York Univ Lab Ind & Appl Math LIAM Dept Math & Stat Toronto ON Canada

Background: Aging often leads to cognitive function decline, sensory structure deterioration, and musculoskeletal system weakening. This impacts postural control during static and dynamic activities like walking, increasing the fall risk among the elderly. Older adults with mild cognitive impairment (MCI) face an elevated fall risk and cognitive decline, magnifying the public health concern. Objective: This study aimed to explore solutions by investigating the effects of a multi-component physical activity program on cognitive and motor functions in MCI patients. Methods: Twenty-three participants were enrolled in the study and assigned into two groups: an intervention group (n = 13;age = 85.7 +/- 5.5 years) and a control group (n = 9;age = 85 +/- 6.7 years). The study spanned two months, with participants engaging in three 60-minute weekly physical exercise sessions. The intervention focused on improving proprioception, muscle strength, and balance. Results: Results demonstrated significant enhancements in physical performance, fall risk reduction, and balance (p < 0.05). Various tests, including the timed up and go test, Unipedal Stance test, Tinetti test, Short Physical Performance Battery, and 6-minute walking test, indicated these improvements. cognitive function was evaluated with the Mini-Mental State Examination, revealing non-significant progress (p > 0.05). Predictive models for outcomes were developed using linear regression analysis during the follow-up stage. Conclusions: This study underscores the effectiveness of a multi-component physical activity program encompassing balance, proprioception, and muscle-strengthening exercises as a non-pharmaceutical approach in improving balance skills and playing a key role in mitigating the risk of falls among old adults with MCI.

关键词： Alzheimer's disease balance cognitive functions fall risk mild cognitive impairment motor functions multicomponent physical exercise older adults proprioception

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Motor and cognitive functions of the ventral premotor cortex

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CURRENT OPINION IN NEUROBIOLOGY 2002年第2期12卷 149-154页

作者： Rizzolatti, G Fogassi, L Gallese, V Univ Parma Ist Fisiol Umana I-43100 Parma Italy Univ Parma Dipartimento Psicol I-43100 Parma Italy

Recent data show that the ventral premotor cortex in both humans and monkeys has motor and cognitive functions. The cognitive functions include space perception, action understanding and imitation. The data also show a clear functional homology between monkey area F5 and human area 44. Preliminary evidence suggests that the ventral part of the lateral premotor cortex in humans may correspond to monkey area F4. A tentative map of the human lateral premotor areas founded on the reviewed evidence is presented.

关键词： cortex bone disorders cognitive functions Monkeys Human Human cognitive function Bone Diseases simians Motor Premotor Cortex Cognition

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EFFECTS OF FLUNITRAZEPAM ON cognitive functions

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PSYCHOPHARMACOLOGY 1989年第2期98卷 251-256页

作者： SMIRNE, S FERINISTRAMBI, L PIROLA, R TANCREDI, O FRANCESCHI, M PINTO, P BAREGGI, SR STATE UNIV MILANO SCH MED DEPT PHARMACOL I-20129 Milan ITALY

The effects of various oral doses (1, 2, 4 mg) of flunitrazepam on vigilance, attention, immediate memory, short-term memory, learning, non-consolidated and consolidated long-term memory were determined. Twelve healthy young male volunteers were given placebo or flunitrazepam in a double-blind, random latin-square sequence, crossing over every 2 weeks. Volunteers completed a battery of tests at night, 3.5 h after drug administration, and in the morning, 10 h after drug administration. Flunitrazepam 1 mg did not significantly impair any of the functions tested at night, while 4 mg impaired vigilance, attention, immediate memory, short-term verbal memory and learning. The impairments of immediate and short-term memory seem to be related and proportional to reductions in vigilance and attention. Doses of 2 mg and 4 mg impaired the speed of learning but did not decrease the amount of material learned. Flunitrazepam caused dose-related impairment of long-term memory, both consolidated and not. This reduction of long-term memory does not seem to be related to the impairments of vigilance, attention or learning. The lowest dose did not modify vigilance and learning in any subject, improved attention in half of the subjects but reduced long-term memory in a similar number of subjects. Therefore, our results indicate selective impairment of long-term memory. Since there were no differences between the effects on consolidated and non-consolidated memory, the amnesic effect of flunitrazepam seems to be due to a decrease in the storage of memory traces. There were no clear generalized residual effects in the morning after administration.

关键词： Amnesia Flunitrazepam Attention Vigilance cognitive functions

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P300 auditory event-related potentials in children with obesity: is childhood obesity related to impairment in cognitive functions?

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PEDIATRIC DIABETES 2011年第7期12卷 589-595页

作者： Tascilar, Mehmet Emre Turkkahraman, Doga Oz, Oguzhan Yucel, Mehmet Taskesen, Mustafa Eker, Ibrahim Abaci, Ayhan Dundaroz, Rusen Ulas, Umit Hidir Gaziantep Children Hosp Dept Pediat Endocrinol Gaziantep Turkey Gulhane Mil Med Fac Dept Pediat Endocrinol Ankara Turkey Gulhane Mil Med Fac Dept Neurol Ankara Turkey Gulhane Mil Med Fac Dept Pediat Ankara Turkey

Objective: To investigate alterations in P300 auditory event-related potentials in children with obesity to detect changes in cognitive functions. Method: A total of 50 children with obesity and 23 age- and sex-matched healthy control subjects were included in the study. Laboratory tests were performed to detect dislipidemia and insulin resistance (IR). The latencies and amplitudes of P300 waves were measured in healthy and obese subjects with or without IR. The oddball paradigm was used in recordings of P300 auditory event-related potentials. Results: A significant difference was observed between groups regarding latency and amplitude of P300 component obtained from central (Cz) electrode. The grand means of P300 latency were longer, and amplitude decreased significantly in obese group compared to that of healthy controls. When the obese group was divided into two different subgroups, those with IR and without IR, the grand means of P300 latency were longer and the amplitude decreased significantly in subjects with IR compared to those without IR. Conclusion: Both decreased amplitude and prolonged latency of P300 are associated with IR in children with obesity, which shows the impairment of neural activity associated with sensory and cognitive information processing in these children. Further studies are necessary to strengthen the current findings and to determine the exact mechanism of cognitive impairment in obese children.

关键词： cognitive functions ERPs obesity P300

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EFFECTS OF PHENYTOIN AND CARBAMAZEPINE ON cognitive functions IN NEWLY-DIAGNOSED EPILEPTIC PATIENTS

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ACTA NEUROLOGICA SCANDINAVICA 1994年第2期89卷 81-86页

作者： PULLIAINEN, V JOKELAINEN, M Department of Neurology Central Hospital of Paijat-Hame SF-15850 Lahti Finland

Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability.

关键词： EPILEPSY PHENYTOIN CARBAMAZEPINE cognitive functions

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Signaling molecules and disturbances of cognitive functions in brain diseases

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NEUROCHEMICAL JOURNAL 2015年第3期9卷 169-180页

作者： Gomazkov, O. A. Russian Acad Med Sci Orekhovich Inst Biomed Chem Moscow Russia

Data on the roles of signaling molecules in the organization and control of cognitive functions of healthy and "ill" brains are analyzed. As an initial mechanism of memory physiology, we determine the complex of biochemical processes that are triggered by signal transmission in a synapse and finish with the fixation of information in the genomic apparatus. The center of these events is a coordinated system that includes transduction, transcription, epigenetic, and regulatory (neurotrophic) proteins. Dissonance of these mechanisms is a primary cause of memory disturbances, cognitive dysfunction, and psychic disorders. We consider the data of experimental and clinical observations on the role of the multilevel system of signaling molecules during aging, neurodegenerative (Alzheimer's), and psychic disorders (depression). However, signaling molecules may be considered as well-defined targets for the development of novel therapeutic approaches.

关键词： brain signaling molecules synapses cognitive functions Alzheimer's disease brain aging epigenetic regulation

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