Impaired Spatial Working Memory Research Articles

Progesterone improves functional outcomes after transient focal cerebral ischemia in both aged male and female rats.

Progesterone hormone (P4) is a promising agent against strokes because post-ischemic administration of P4 exerts neuroprotective effects in several young and aged animal models of stroke. However, in contrast to a majority of the studies using male animals, female animals remain underrepresented. In addition, we do not know whether the same administration way of P4 is effective in both male and female animals because there are gender different responses to steroid hormones and stroke. In this study, we thus evaluated long-term histological and functional outcomes in the same treatment with P4 in both 18-month old male and age-matched female rats subjected to transient middle cerebral artery occlusion (MCAO). MCAO aged male and female rats were given a subcutaneous injection of P4 (4 mg/kg) 6 h after MCAO followed by once daily for successive 7 days. The post-ischemic administration of P4 significantly improved the impairments of spatial working memory and motor coordination 28-29 days after MCAO in both aged male and age-matched female rats. However, the P4 administration slightly but not significantly reduced infarct sizes 30 days after MCAO in aged female rats, in contrast to significant better histological outcome in P4-treated aged males. On the other hand, these histological and behavioral analyses showed no adverse effects of P4 in aged rats of both sexes. Collectively, our study provides preclinical evidence to prompt further preclinical studies for post-stroke treatment with P4 and the translation of its clinical trials in old stroke patients of both sexes.

Ginsenoside Rb1 Ameliorates Working Memory Deficits Via Regulation of Prefrontal Cortical Gabaergic Transmission in MPTP-Treated Mice

Background: Working memory impairment is a common non-motor symptom in the progression of Parkinson's disease (PD). Ginsenoside Rb1, an extract from the Ginseng root, has been demonstrated to ameliorate motor deficits and prevent dopaminergic neuron death in PD. However, whether Rb1 can attenuate the PD-associated deficits in working memory and its underlying mechanism of action are still unclear. Methods: Behavioral tests were used to examine the effect of Rb1 on the working memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Gamma-aminobutyric acid (GABA)-chemical exchange saturation transfer (CEST) magnetic resonance imaging and electrophysiology were used to identify the effect of Rb1 on the GABA content and GABAergic synaptic transmission in the prefrontal cortex. Immunofluorescence and western blotting were used to explore the expression of the different GABA receptors. Findings: We found that Rb1 attenuated the impairment in spatial working memory in the MPTP mouse model of PD, and this neuroprotective mechanism involved the regulation of prefrontal cortical GABAergic content and transmission. We demonstrated that Rb1 increased GABA content in the prefrontal cortex, and Rb1 prevented the MPTP-induced decrease of presynaptic GABA release and postsynaptic GABA receptor expression and function. Furthermore, Rb1's promotion of GABA current may be associated with the regulation of GABAA receptor trafficking from the postsynaptic density to the membrane, as well as with the modulation of postsynaptic GABAB receptors to enhance GABAA receptor function. Interpretation: Rb1 may serve as a potential drug candidate for the treatment of cognitive impairments in PD. Funding: The National Natural Science Foundation of China (No. 81704130 to YZ, No. 81774377 and No. 81373999 to LW), the Natural Science Foundation of Fujian Province of China (No. 2017J05139 to YZ), the Natural Science Foundation of Guangdong Province of China (No. 2017A030310643 to YZ), the China Postdoctoral Science Foundation (No. 2016M590598 to YZ), the National Key Research and Development Program of China (No. 2016YFC1305903 to LW), and the Program for New Century Excellent Talents in University of Ministry of Education of China (No. NCET-13-0505 to LW). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: All experiments were conducted according to the National Institute of Health guidelines on the care and use of animals (NIH Publications No. 8023, revised 1978) and approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University.

Inhibition of miR-155 Limits Neuroinflammation and Improves Functional Recovery After Experimental Traumatic Brain Injury in Mice.

Micro-RNAs (miRs) are short, noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and have been implicated in the pathophysiology of secondary damage after traumatic brain injury (TBI). Among miRs linked to inflammation, miR-155 has been implicated as a pro-inflammatory factor in a variety of organ systems. We examined the expression profile of miR-155, following experimental TBI (controlled cortical impact) in adult male C57Bl/6 mice, as well as the effects of acute or delayed administration of a miR-155 antagomir on post-traumatic neuroinflammatory responses and neurological recovery. Trauma robustly increased miR-155 expression in the injured cortex over 7days. Similar TBI-induced miR-155 expression changes were also found in microglia/macrophages isolated from the injured cortex at 7days post-injury. A miR-155 hairpin inhibitor (antagomir; 0.5nmol), administered intracerebroventricularly (ICV) immediately after injury, attenuated neuroinflammatory markers at both 1day and 7days post-injury and reduced impairments in spatial working memory. Delayed ICV infusion of the miR-155 antagomir (0.5nmol/day), beginning 24h post-injury and continuing for 6days, attenuated neuroinflammatory markers at 7days post-injury and improved motor, but not cognitive, function through 28days. The latter treatment limited NADPH oxidase 2 expression changes in microglia/macrophages in the injured cortex and reduced cortical lesion volume. In summary, TBI causes a robust and persistent neuroinflammatory response that is associated with increased miR-155 expression in microglia/macrophages, and miR-155 inhibition reduces post-traumatic neuroinflammatory responses and improves neurological recovery. Thus, miR-155 may be a therapeutic target for TBI-related neuroinflammation.

Heritability estimates of spatial working memory and set-shifting in a healthy Chinese twin sample: A preliminary study.

Impairments in spatial working memory (SWM) and set-shifting abilities have both been consistently observed in individuals with schizophrenia and are considered to be potential endophenotypes of this illness. However, an endophenotype needs to fulfill a set of stringent criteria, including heritability. This study examined the heritability of these two functions in a healthy Chinese twin sample. Forty-five pairs of monozygotic (MZ) twins and 35 pairs of dizygotic (DZ) twins completed the SWM task and the Intra-Extra Dimensional Set-Shifting (IED) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We found a moderate heritability for SWM, of which the familial/genetic factors accounted for 33% of the total variance. However, we failed to find any significant heritability for set-shifting ability, of which the specific environmental factor explained most of the variance (85%). The preliminary findings from this small healthy Chinese twin sample suggest that SWM is heritable, whereas the set-shifting ability may reflect "extra-genetic" influences.

Effects of methylphenidate on cognition and behaviour in children with neurofibromatosis type 1: a study protocol for a randomised placebo-controlled crossover trial

IntroductionDopamine dysregulation has been identified as a key modulator of behavioural impairment in neurofibromatosis type 1 (NF1) and a potential therapeutic target. Preclinical research demonstrates reduced dopamine in the brains...

Gene expression dynamics following mithramycin treatment: A possible model for post-chemotherapy cognitive impairment.

Chemotherapy-induced cognitive changes is a major burden on a substantial number of cancer survivors. The mechanism of this sequel is unknown. In this study, we followed long-term effects of early in life mithramycin (MTR) treatment on behaviour and on the normal course of alterations of gene expression in brain. Between post-natal days (PND) 7 and 10, male rats were divided into 2 groups, 1 receiving MTR (0.1mg/kg s.c. per day) and the other receiving saline. At PND11, frontal cortex tissue samples were dissected from 4 rats from each group. At PND 65 the remaining rats underwent behavioural tests after which all the rats were decapitated and their prefrontal cortex incised. Rats treated transiently with MTR early in life, showed impairments in spatial working memory and anxious-like behaviour in adulthood. The immediate molecular effect of MTR was expressed in a limited number of altered genes of different unconnected trajectories, which were simultaneously distorted by the drug. In contrast, 3months later we observed a change in the expression of more than 1000 genes that converged into specific cellular processes. Time-dependent gene expression dynamics of several genes was significantly different between treated and untreated rats. The differences in the total number of altered genes and in gene expression trends, immediately and long after MTR treatment cessation, suggest the evolution of a new cellular homeostatic set point, which can lead to behavioural abnormalities following chemotherapy treatment.

Impairment of spatial working memory and oxidative stress induced by repeated crack cocaine inhalation in rats

Crack cocaine is a highly toxic drug with great potential to induce addiction. It produces more intense effects than cocaine powder, with its use having grown worldwide. However, few studies have focused on the cognitive and biochemical consequences that result from crack cocaine inhalation. This study examined the effects of direct crack cocaine inhalation on spatial working memory and brain oxidative stress parameters in rats. Male adult Wistar rats, well-trained in an eight-arm radial maze (8-RM), underwent five sessions of crack cocaine inhalation (crack cocaine group) once a day or inhalation simulation (sham group), being tested in 1-h delayed tasks 24 h after the last inhalation. An additional inhalation session was carried out the following day, with the prefrontal cortex, hippocampus and striatum being removed five minutes afterwards in order to assess oxidative damage such as lipid peroxidation, thiobarbituric acid-reactive species (TBARS) levels, and advanced oxidation protein products (AOPP), as well as the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Animals from the crack cocaine group showed more errors (p < 0.01) in the 1-h post-delay performance in the 8-RM when compared to the sham group. The crack cocaine group showed decreased (p < 0.05) lipid peroxidation in the hippocampus and increased (p < 0.001) levels of AOPP and SOD activity (p < 0.05) in the striatum when compared to the sham group. Therefore, the repeated inhalation of crack cocaine impaired long-term spatial working memory and elicited oxidative stress in the hippocampus and striatum of rats.

Dual co-agonist CI-1206 antagonizes Aβ1-42-induced impairments in spatial learning and memory in mice

To study the neuroprotective effects of a novel GIP/GLP-1 receptor dual agonist CI-1206 against Aβ1-42-induced impairments in spatial working memory and long term memory in mice. C57 mice, after receiving intracerebralventricular (i.c.v.) injection of Aβ1-42 and intraperitoneal injection of CI-1206, were divided into the following groups:saline+D-PBS, Aβ1-42+saline, CI-1206+D-PBS and Aβ1-42+CI-1206 group (n=12). Y maze spontaneous alternation of mice was tested to assess short term working memory, and Morris water maze task was used to assess long term reference memory. ①The percentage of right alternation of mice in Aβ1-42+saline group was significantly decreased, while the percentage in Aβ1-42+CI-1206 group was significantly larger than that in Aβ1-42 alone group (P<0.05). ②In Morris water maze test, the escape latency of mice in Aβ1-42+saline group showed a significant increase, with a significant decline in swimming time in target quadrant. Treatment with CI-1206 significantly antagonized these detrimental effects induced by Aβ1-42. ③Aβ1-42 and CI-1206 did not affect the motor ability and vision of mice. I.C.V. administration of Aβ1-42 impaired the short term and long term spatial memory of mice, while CI-1206 could effectively antagonize the detrimental effects.

Maternal Breathing Dysfunction During Pregnancy Alters Microglial Activities and Increases Risk for Psychiatric Disorders in Her Offspring

Each year, over half a million women develop sleep disordered breathing (SDB) by the third trimester, the prevalence of which is increasing in parallel with the obesity epidemic. While negative consequences of SDB during pregnancy on the health of the mother and newborn are becoming better appreciated, nothing is known about the impact of SDB on the neural function of her offspring. SDB is a potent inflammatory stimulus, inducing chronic inflammation that contributes to many of the morbidities associated with SDB. Since epidemiological studies suggest that maternal inflammation is associated with the development of neuropsychiatric disorders in her offspring, we tested the hypothesis that in utero intermittent hypoxia impairs cognitive behavior in the offspring. Pregnant rat dams were exposed to chronic intermittent hypoxia (8 hrs/day, 2 min 10.5% O2 separated by 2 min of 21% O2) or normoxia from gestation days 10–21 (GIH and GNX, respectively). Juvenile (3 week) and adult (8 week) offspring were tested in a Y‐maze spontaneous alternation task, a well‐validated index of spatial working memory. We found that spontaneous alternation performance was severely impaired in juvenile and adult male GIH offspring relative to GNX offspring, suggesting GIH results in early developmental emergence of working memory impairments. In contrast, female GIH offspring did not exhibit impairments in spatial working memory at either age. Microglia isolated from the forebrain of male GIH offspring exhibited significant reductions in the expression of the phagocytic receptor gene complement receptor 3 (CD11b), suggesting that GIH impairs microglial synaptic pruning activities. In the same samples, expression levels of DNA methyltransferase enzymes (DNMTs), that are responsible for repressing gene expression, were increased. Since hypoxia enriches the transcriptional activation mark H3K4me3 in microglial cultures, we hypothesize that GIH upregulates DNMT gene expression via epigenetic histone alterations to fetal microglia, which represses microglial phagocytic gene expression. Together, these data suggest that GIH: 1) sex‐dependently alters cognitive phenotypes in GIH offspring, and 2) may induce epigenetic suppression of microglial phagocytic activities that impair microglial synaptic pruning during development, altering forebrain synaptic connectivity in male offspring.Support or Funding InformationSupported by R01 NS085226 (JJW) and HL105511 (TLB)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Emotional working memory in patients with major depressive disorder.

ObjectiveThis study was performed to examine the working memory (WM) encoding and retrieval abilities in patients with major depressive disorder (MDD) and determine whether a mood-congruent memory effect is present.MethodsThe modified Sternberg WM paradigm with positive, negative, and neutral emotional pictures was used to investigate the WM abilities of 26 patients with MDD and 26 healthy controls (HCs).ResultsNo significant difference in picture WM was found between the MDD and HC groups; however, the accuracy of picture position WM was significantly lower and the response time was significantly longer in the MDD than HC group, regardless of the picture or position WM. Additionally, in the MDD group, the accuracy of negative picture/position WM was significantly higher than that of positive picture/position WM.ConclusionsThese results suggest that in patients with MDD, spatial WM impairment was more severe than object WM. In addition, these patients’ WM retrieval was impaired, resulting in a decrease in WM retrieval ability, which may be an important cause of the slow thought in patients with MDD. Moreover, patients with depression have a mood-congruent memory effect, which may be an important factor in the occurrence and maintenance of depression.

Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat.

The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral midline thalamus is an important anatomical link between the HF and mPFC, and as such is crucially involved in SWM functions that recruit both structures. Little is known, however, regarding the role of RE in other behaviors mediated by this circuit. In the present study, we examined the role of RE in spatial working memory and executive functioning following reversible inactivation of RE with either muscimol or procaine. Rats were implanted with an indwelling cannula targeting RE and trained in a delayed nonmatch to sample spatial alternation T-maze task. For the task, sample and choice runs were separated by moderate or long delays (30, 60, and 120 s). Following asymptotic performance, rats were tested following infusions of drug or vehicle. Muscimol infused into RE impaired SWM at all delays, whereby procaine only impaired performance at the longest delays. Furthermore, RE inactivation with muscimol produced a failure in win-shift strategy as well as severe spatial perseveration, whereby rats persistently made re-entries into incorrect arms during correction trials, despite the absence of reward. This demonstrated marked changes in behavioral flexibility and response strategy. These results strengthen the role of nucleus reuniens as a pivotal link between hippocampus and prefrontal cortex in cognitive and executive functions and suggest that nucleus reuniens may be a potential target in the treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity disorder, addiction, and obsessive-compulsive disorder, whose symptoms are defined by hippocampal-prefrontal dysfunctions.

Orexin knockout mice exhibit impaired spatial working memory

Orexins play a crucial role in the maintenance of arousal and are involved in the modulation of diverse physiological process, including cognitive function. Recent data have suggested that orexins are involved in learning and memory processes. The purpose of this study was to assess the effects of orexin deficiency on working memory. A delayed non-matching-to-place T-maze task was used to evaluate spatial working memory in mice lacking orexin prepro-peptide (orexin knockout; KO) and wild-type controls. We demonstrated that the number of correct choices in the orexin KO mice became lower than that of the controls over training. In an object exploration task, the controls explored the displaced object more than the mutants did, whereas this difference was not observed for the nondisplaced objects in either group. The orexin KO mice showed locomotor activity comparable to the control mice in terms of total distance traveled across training in both the object exploration task and the open field test. These findings indicate that the orexin system plays an important role in working memory of spatial cues.

Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse

IntroductionTranslational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease. MethodsWe used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics. ResultsPosiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8-norPosiphen. DiscussionThis is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.

Ethyl pyruvate prevents from chronic cerebral hypoperfusion via preserving cognitive function and decreasing oxidative stress, caspase 3 activation and IL-1β level.

One of the important risk factors for dementia is chronic cerebral hypoperfusion (CCH) especially in patients with cerebrovascular disease. In the present study, using rat model of bilateral common carotid artery occlusion, the possible protective effects of ethyl pyruvate (EP) have been explored in terms of memory impairment, oxidative stress, and levels of caspase-3, Na-K ATPase, and IL- 1β. Rats were treated with EP (50 mg/kg, i.p) for 4 weeks. Cognitive function was evaluated by Morris Water Maze (MWM). Both levels of caspase-3 and Na-K ATPase in tissue, IL-1β in plasma were measured by ELISA method. Status of oxidative stress in brain was assessed by the measurements of the tissue malondialdehyde (MDA) and reduced glutathione (GSH) contents. RESULTS: Results showed that CCH caused a striking impairment of spatial working memory, accompanied with increased levels of MDA and IL-1β as well as caspase 3 level. The treatment with EP, however, significantly improved the memory impairment. Moreover, the treatment also provided beneficial effects on the disturbances of caspase 3, IL-1β and MDA. This study strongly imply that the EP administration can alleviate the memory impairment observed due to CCH. The protection provided by EP may result from inhibition of inflammatory response, apoptotic processes and oxidative stress (Fig. 3, Ref. 58).

Spatial working memory performance following acute sport-related concussion

Introduction An important problem in the field of sport-related concussion is the lack of a ‘gold-standard’ clinical assessment tool. Currently, the diagnosis relies heavily on self-reporting of symptoms and observation of clinical signs by medical professionals. To address this, our group has been motivated to develop objective measures of neurological impairment following concussion. Spatial working memory is an important aspect of cognitive function that might be impaired following concussion. In the present study, we measured spatial working memory using a robotic spatial span task. We first assessed test–retest reliability in 82 healthy athletes who underwent baseline testing across two athletic seasons using intraclass correlation coefficients. We then assessed spatial span performance relative to baseline in 47 athletes acutely following sport-related concussion using a reliable change index with 80% confidence limits to define impairment on an individual basis. Results We found good test–retest reliability for the mean span (a measure of spatial working memory span length; intraclass correlation coefficient = 0.79), and moderate reliability for the response duration (time taken per spatial target; intraclass correlation coefficient = 0.64) in healthy athletes. However, only 19% of acutely concussed athletes showed evidence of impairment relative to baseline in mean span, and even fewer (9%) showed evidence of impairment in response duration. Analysis of serial position curves revealed primacy and recency effects for this task, but no group-level differences between concussed and healthy athletes. Analysis of specific types of errors showed a higher rate of substitution errors in the concussed group at baseline, suggesting possible malingering in a small number of athletes. Conclusion Overall, few athletes showed evidence of impaired spatial working memory acutely following concussion, suggesting either that spatial working memory is not commonly impaired acutely post-concussion, or that the present task is not sufficiently demanding.

Component deficits of visual neglect: “Magnetic” attraction of attention vs. impaired spatial working memory

Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative component deficits of neglect, rightward "magnetic" attraction of attention and impaired spatial working memory, in a group of 47 right brain-damaged patients, of whom 33 had signs of left neglect. Patients performed a visual search task on three distinct conditions, whereby touched targets could (1) be tagged, (2) disappear or (3) show no change. Magnetic attraction of attention was defined as more left neglect on the tag condition than on the disappear condition, where right-sided disappeared targets could not capture patients' attention. Impaired spatial working memory should instead produce more neglect on the no change condition, where no external cue indicated that a target had already been explored, than on the tag condition. Using a specifically developed analysis algorithm, we identified significant differences of performance between the critical conditions. Neglect patients as a group performed better on the disappear condition than on the no change condition and also better in the tag condition comparing with the no change condition. No difference was found between the tag condition and the disappear condition. Some of our neglect patients had dissociated patterns of performance, with predominant magnetic attraction or impaired spatial working memory. Anatomical results issued from both grey matter analysis and fiber tracking were consistent with the typical patterns of fronto-parietal and occipito-frontal disconnection in neglect, but did not identify lesional patterns specifically associated with one or another deficit, thus suggesting the possible co-localization of attentional and working memory processes in fronto-parietal networks. These findings give support to the hypothesis of the co-occurrence of distinct cognitive deficits in visual neglect and stress the necessity of multi-component models of visuospatial disorders.

Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy.

The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogenesis in the hippocampus and memory deficits induced by valproic acid (VPA). In the present study, we investigated the preventive effects of AA on the deficits in spatial working memory and cell proliferation and survival caused by 5-FU chemotherapy in a rat model. Male Sprague Dawley rats received 5-FU (5 i.v. injections, 25 mg/kg) on day 8, 11, 14, 17 and 20 of the study. This was co-administered with AA (30 mg/kg, oral gavage tube) either 20 days before receiving 5-FU (preventive), after receiving 5-FU (recovery), or for the entire period of the experiment (throughout). Spatial working memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival of dividing cells were quantified using immunohistochemistry. Rats in the 5-FU alone and recovery groups showed memory deficits in the NOL test and reductions in cell proliferation and cell survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Rats in the control, AA alone, and both preventive and throughout co-administration groups, however, did not exhibit these characteristics. The results showed that 5-FU chemotherapy impaired memory and reduced cell proliferation and cell survival in the SGZ of the hippocampal dentate gyrus. However, these impairments in the animals receiving 5-FU chemotherapy were restored to control levels when AA was co-administered before and during 5-FU treatment. These data demonstrate that AA can prevent the spatial working memory and hippocampal neurogenesis impairments caused by 5-FU chemotherapy.

Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion is a major cause of age-related vascular cognitive impairment. A well-characterised mouse model has shown that hypoperfusion results in gliovascular and white matter damage and impaired spatial working memory. In this study, we assessed whether cilostazol, a phosphodiesterase III inhibitor, could protect against these changes. Adult, male C57Bl/6J mice were subjected to bilateral common carotid artery stenosis or a sham operation and fed normal or cilostazol diet for three months. Cilostazol treatment reduced the impairment in working memory and white matter function after hypoperfusion. Endothelial adhesion molecules and gliosis, increased after hypoperfusion, were ameliorated with cilostazol treatment. Interestingly, the improvement in working memory was closely correlated with reduced microglia and endothelial adhesion molecules. Further, the number of stroke lesions after hypoperfusion was reduced in the cilostazol-treated group. Altogether cilostazol showed potential to ameliorate the gliovascular damage and working memory impairments after hypoperfusion possibly via endothelial protection supporting its potential use in the treatment of vascular cognitive impairment.

Physio-somatic symptoms in schizophrenia: association with depression, anxiety, neurocognitive deficits and the tryptophan catabolite pathway.

To investigate the frequency of physio-somatic symptoms (PS) symptoms in schizophrenia and their relation to positive, negative and affective symptoms; neurocognitive deficits and impairments in the tryptophan catabolite (TRYCAT) pathway. Eighty four patients with schizophrenia and 40 healthy controls were assessed using the 12 item Fibromyalgia and Chronic Fatigue Syndrome Rating scale (FF) and scales for negative and positive symptoms, depression and anxiety. Cognitive functioning was tested using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Other assessments included: immunoglobulin (Ig)A and IgM responses to tryptophan catabolites (TRYCATs), namely quinolinic (QA), 3-OH-kynurenine (3HK), picolinic (PA), xanthurenic (XA) and kynurenic acid (KA) and anthranilic acid (AA). More than 50% of the patients studied had elevated levels of physio-somatic (PS) symptoms, significantly co-occurring with depression and anxiety, but not with negative or positive symptoms. PS symptoms were significantly associated with IgA/IgM responses to TRYCATs, including increased IgA responses to 3 HK, PA and XA, and lowered IgA to QA and AA. Fatigue, muscle pain and tension, autonomic and cognitive symptoms and a flu-like malaise were strongly associated with cognitive impairments in spatial planning and working memory, paired associative learning, visual sustained attention and attention set shifting. PS symptoms in schizophrenia aggregate with depression and anxiety symptoms and may be driven by TRYCAT patterning of IgA/IgM-responses, with IgA indicating mucosal-mediated changes and IgM indicating regulatory functions. As such, the patterning of IgA/IgM responses to TRYCATs may indicate differential TRYCATs regulation of neuronal and glia activity that act to regulate PS signalling in schizophrenia.

Cognitive enhancement activity of turmeric oil in amyloid beta (25-35) induced Alzheimers model

Introduction: Turmeric oil (TMO) is a secondary metabolite of Curcuma longa Linn obtained by steam distillation of its rhizomes. It contains 50% ar-Turmerone as a major constituent. The antioxidant, anti-bacterial and anti- inflammatory activities of the Turmeric oil have already been established. It has been reported that, Curcumin (CM) is having a protective role in neuro inflammation and beneficial in Alzheimers disease (AD). But the effect of TMO (fraction without CM) is not explored till now. Aim: To evaluate the cognitive enhancement activity of turmeric oil using Amyloid Beta induced Alzheimers model and comparing it with that of Curcumin. Methodology: An ICV injection was performed to administer A? (25-35) peptide to both the lateral ventricles of the Wistar albino rats. Turmeric oil (400mg/kg), Curcumin (400mg/kg) and Donepezil (DPL) 10mg/kg were suspended in sunflower oil and administered orally from the second day of ICV injection. After 16 days of recovery period, in-vivo screening for spatial working, spatial learning and recognition memory were performed by Radial arm maze, Morris water maze and Novel object recognition task respectively. In-vitro study of acetyl cholinesterase inhibitory activity was also performed by modified Ellmans method. Results: TMO significantly reduced the number of wrong entries in Radial arm maze compared to the A? group. DPL showed maximum reduction in number of wrong entries followed by CM and TMO. In Morris water maze task, TMO significantly reduced the escape latency when compared to the A? group. The effect of DPL in escape latency was more significant compared to CM and TMO. In Novel object recognition task, TMO could not alter the percentage time spent on the novel object compared to the A? group. DPL and CM significantly increased the percentage time spent on the novel object. Acetyl cholinesterase inhibitory activity of TMO, CM and DPL were 53.37%, 58.26% and 66.35% respectively at 10mg/ml concentration which denotes the enhancement of acetyl choline in brain. TMO provides a significant protection against spatial working and learning memory impairment, while its effect was not much affected in recognition memory impairment. Conclusion: It is concluded that Turmeric oil enhances the cognitive activity compared to Curcumin and Donepezil.