The association between low cognitive reserve and subjective memory complaints in functionally independent older women.

BACKGROUND: Several factors have been found to defend against pathologic cognitive decline in aging (i.e., cognitive reserve [CR]); however, other factors, including subjective memory complaints (SMC) and decreased functionality are considered early indicators of underlying neurocognitive dysfunction. Despite these known associations, the relationship between the presence of CR and SMC remains equivocal. This study sought to determine the relationship between objectively measured CR and SMC in a sample of functionally independent older women. METHODS: This cross-sectional study recruited women aged ≥60 years who attended fitness or continuing education programs at the University for Seniors in Mexico City. Participants underwent a battery of physical and cognitive evaluations, including the Cognitive Reserve Questionnaire (CRQ), and were asked probing questions used to identify the presence of SMC. RESULTS: The 269 participants had a median age of 69 years; most were single (40.5 %), lived alone (32.7 %), retired (58.2 %), well-educated (≥12 years of education), and functionally independent (89.2 %). 62 % scored "high" on the CRQ, while 9.3 % scored "low". After adjusting for multiple covariates, an independent association between CRQ score and the probability to have SMC was found (adjusted OR = 0.87, 95% CI 0.80-0.95, p-value = 0.002). CONCLUSIONS: This study identified a relationship between low CR and the presence of SMC, independently of the cognitive function and motoric marker of muscle strength (i.e., low gait speed and handgrip strength) in functionally independent older women over 60y. This relationship remains independent of other variables such as age, symptoms of depression and instrumented activities of daily living.

Association of Being Accompanied at Medical Consultation and Having Memory Complaints With Cognitive Impairment in Elderly Brazilian Outpatients.

BACKGROUND: The usefulness of both the presence of a companion at the medical consultation and patient's cognitive complaints as selection strategies for performing a dementia evaluation is still unclear. OBJECTIVES: To estimate the association of elderly patients being accompanied during medical visits and patient's memory complaint with objective cognitive impairment. METHODS: We included elderly outpatients awaiting medical consultations in 3 non-neurological medical specialties. Demographic and Mini-Mental State Examination were collected. Patients' memory complaints were evaluated with a single question to both patients and companions. RESULTS: Five hundred ninety-three elderly patients were included in the study with 64.6% female and median (interquartile range) age 73 (68-78), 4 (2-6) years of education. Of these, 242 patients were accompanied and 62.6% presented memory complaints. The median (interquartile range) Mini-Mental State Examination scores were significantly lower in patients accompanied and in those with memory complaints. In a logistic regression model, age, education, memory complaint, and presence of companion were associated with cognitive impairment. In the model including only accompanied patients, only age and companion memory complaints were associated with objective cognitive impairment. CONCLUSIONS: The presence of a companion during a clinical consultation and patients' memory complaints are both synergistically associated with objective cognitive impairment.

Preliminary comparative study of cortical thickness in HIV-infected patients with and without working memory deficit.

PURPOSE: Changes in cerebral cortical regions occur in HIV-infected patients, even in those with mild neurocognitive disorders. Working memory / attention is one of the most affected cognitive domain in these patients, worsening their quality of life. Our objective was to assess whether cortical thickness differs between HIV-infected patients with and without working memory deficit. METHODS: Forty-one adult HIV-infected patients with and without working memory deficit were imaged on a 1.5 T scanner. Working memory deficit was classified by composite Z scores for performance on the Digits and Letter-Number Sequencing subtests of the Wechsler Adult Intelligence Scale (third edition; WAIS-III). Cortical thickness was determined using FreeSurfer software. Differences in mean cortical thickness between groups, corrected for multiple comparisons using Monte-Carlo simulation, were examined using the query design estimate contrast tool of the FreeSurfer software. RESULTS: Greater cortical thickness in left pars opercularis of the inferior frontal gyrus, and rostral and caudal portions of the left middle frontal gyrus (cluster 1; p = .004), and left superior frontal gyrus (cluster 2; p = .004) was observed in HIV-infected patients with working memory deficit compared with those without such deficit. Negative correlations were found between WAIS-III-based Z scores and cortical thickness in the two clusters (cluster 1: ρ = -0.59; cluster 2: ρ = -0.47). CONCLUSION: HIV-infected patients with working memory deficit have regions of greater thickness in the left frontal cortices compared with those without such deficit, which may reflect increased synaptic contacts and/or an inflammatory response related to the damage caused by HIV infection.

Low Speech Connectedness in Alzheimer's Disease is Associated with Poorer Semantic Memory Performance.

Connected speech is an everyday activity. We aimed to investigate whether connected speech can differentiate oral narrative production between adults with Alzheimer's disease (AD; n = 24) and cognitively healthy older adults (n = 48). We used graph attributes analysis to represent connected speech. Participants produced oral narratives and performed semantic, episodic, and working memory tasks. AD patients produced less connected narratives than cognitively healthy older adults. Connectedness was associated with semantic memory in AD and with episodic memory in controls. Word-graphs connectedness represents a practical tool to assess cognitive impairment in AD patients.

Acrobatic exercise recovers object recognition memory impairment in hypoxic-ischemic rats.

Neonatal hypoxia-ischemia (HI) can lead to cognitive impairments and motor dysfunction. Acrobatic exercises (AE) were proposing as therapeutic option to manage HI motor deficits, however, the cognitive effects after this treatment are still poorly understood. Therefore, we evaluated the effects of AE protocol on memory impairments and brain plasticity markers after Rice-Vannucci HI rodent model. Wistar rats on the 7th postnatal day (PND) were submitted to HI model and after weaning (PND22) were trained for 5 weeks with AE protocol, then subsequently submitted to cognitive tests. Our results showed recovery in novel object recognition (NOR) memory, but not, spatial Morris Water Maze (WM) memory after AE treatment in HI rats. BDNF and synaptophysin neuroplasticity markers indicate plastic alterations in the hippocampus and striatum, with maintenance of synaptophysin despite the reduction of total volume tissue, besides, hippocampal HI-induced ipsilateral BDNF increased, and striatum contralateral BDNF decreased were noted. Nevertheless, the exercise promoted functional recovery and seems to be a promising strategy for HI treatment, however, future studies identifying neuroplastic pathway for this improvement are needed.

Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease.

Importance: Recent studies have suggested that unawareness, or anosognosia, of memory decline is present in predementia stages of Alzheimer disease (AD) and may serve as an early symptomatic indicator of AD. Objective: To investigate the evolution of anosognosia of memory decline in individuals who carry the PSEN1 E280A variant for autosomal dominant AD compared with family members who do not carry the variant. Design, Setting, and Participants: This cohort study investigated a total of 2379 members of a Colombian kindred with autosomal dominant AD who were part of the Alzheimer's Prevention Initiative Registry. Assessments were completed at the University of Antioquia, Colombia, with data collected between January 1, 2000, and July 31, 2019. Main Outcomes and Measures: Awareness of memory function was operationalized using the discrepancy between self-report and study partner report on a memory complaint scale. Linear mixed effects models were used to assess memory self-awareness over age separately in variant carriers and noncarriers. Results: This study included 396 variant carriers (mean [SD] age, 32.7 [11.9] years; 200 [50.5%] female), of whom 59 (14.9%) were cognitively impaired, and 1983 cognitively unimpaired noncarriers (mean [SD] age, 33.5 [12.5] years; 1129 [56.9%] female). The variant carriers demonstrated increased awareness until the mean (SD) age of 35.0 (2.0) years and had anosognosia at approximately 43 years of age, approximately 6 years before their estimated median age of dementia onset (49 years; 95% CI, 49-51 years). Cognitively unimpaired noncarriers reported more complaints than their study partners aged 20 and 60 years (10.1 points, P < .001). On the awareness index, a decrease with age (mean [SE] estimate, -0.04 [0.02] discrepant-points per years; t = -2.2; P = .03) in the noncarriers and in the variant carriers (mean [SE] estimate, -0.21 [0.04] discrepant-points per years; t = -5.1; P < .001) was observed. Conclusions and Relevance: In this cohort study, increased participant complaints were observed in both groups, suggesting that increased awareness of memory function was common and nonspecific to AD in this cohort. In variant carriers, awareness of memory function decreased in the predementia stages, reaching anosognosia close to the age of mild cognitive impairment onset, providing support for the usefulness of awareness of memory decline.

Head injury and neuropsychiatric sequelae in asylum seekers.

OBJECTIVE: Asylum seekers experience a high burden of physical and psychological trauma, yet there is a scarcity of literature regarding the epidemiology and sequelae of head injury (HI) in asylum seekers. We examined HI prevalence and association with neuropsychiatric comorbidities in asylum seekers. METHODS: A retrospective cross-sectional study was performed through review of 139 medical affidavits from an affidavit database. Affidavits written from 2010 to 2018 were included. Demographic and case-related data were collected and classified based on the presence of HI. For neuropsychiatric sequelae, the primary study outcome was headache and the secondary outcomes were depression, posttraumatic stress disorder, and anxiety. Multivariable logistic regression was performed to examine the association between HI and neuropsychiatric sequelae, adjusted for demographic and clinical characteristics. RESULTS: A total of 139 medical affidavits of asylum seekers were included. The mean age was 27.4 ± 12.1 years, 56.8% were female, and 38.8% were <19 years. Almost half (42.5%) explicitly self-reported history of HI. Compared to clients who did not report HI, clients with HI were older and more likely to report a history of headache, physical abuse, physical trauma, concussion, and loss of consciousness. After adjustment for demographic and clinical characteristics, clients with HI had greater odds for neuropsychological sequelae such as headache (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0-8.7) and depression (OR 2.5, 95% CI 1.1-5.7). CONCLUSIONS: We observed a high prevalence of HI in asylum seekers. Comprehensive screening for HI and neuropsychiatric comorbidities is encouraged when evaluating asylum seekers.

Taking advantage of fear generalization-associated destabilization to attenuate the underlying memory via reconsolidation intervention.

Upon retrieval, an aversive memory can undergo destabilization and reconsolidation. A traumatic-like memory, however, may be resistant to this process. The present study sought to contribute with a strategy to overcome this potential issue by investigating whether generalized fear retrieval is susceptible to destabilization-reconsolidation that can be pharmacologically modified. We hypothesized that exposure to a context that elicits moderate generalization levels would allow a malleable memory state. We developed a fear conditioning protocol in context A (cxt-A) paired with yohimbine administration to promote significant fear to a non-conditioned context B (cxt-B) in rats, mimicking the enhanced noradrenergic activity reported after traumatic events in humans. Next, we attempted to impair the reconsolidation phase by administering clonidine (CLO) immediately after exposure to cxt-A, cxt-B, or a third context C (cxt-C) neither conditioned nor generalized. CLO administered post-cxt-B exposure for two consecutive days subsequently resulted in decreased freezing levels in cxt-A. CLO after cxt-B only once, after cxt-A or cxt-C in two consecutive days, or independently of cxt-B exposures did not affect fear in a later test. A 6-h-delay in CLO treatment post-cxt-B exposures produced no effects, and nimodipine administered pre-cxt-B exposures precluded the CLO action. We then quantified the Egr1/Zif268 protein expression following cxt-B exposures and CLO treatments. We found that these factors interact to modulate this memory destabilization-reconsolidation mechanism in the basolateral amygdala but not the dorsal CA1 hippocampus. Altogether, memory destabilization can accompany generalized fear expression; thus, we may exploit it to potentiate reconsolidation blockers' action.

The GLP-1 receptor agonist liraglutide reverses mania-like alterations and memory deficits induced by D-amphetamine and augments lithium effects in mice: Relevance for bipolar disorder.

Metabolic and psychiatric disorders present a bidirectional relationship. GLP-1 system, known for its insulinotropic effects, has also been associated with numerous regulatory effects in cognitive and emotional processing. GLP-1 receptors (GLP-1R) agonists present neuroprotective and antidepressant/anxiolytic properties. However, the effects of GLP-1R agonism in bipolar disorder (BD) mania and the related cognitive disturbances remains unknown. Here, we investigated the effects of the GLP-1R agonist liraglutide (LIRA) at monotherapy or combined with lithium (Li) against D-amphetamine (AMPH)-induced mania-like symptoms, brain oxidative and BDNF alterations in mice. Swiss mice received AMPH 2 mg/kg or saline for 14 days. Between days 8-14, they received LIRA 120 or 240 µg/kg, Li 47.5 mg/kg or the combination Li + LIRA, on both doses. After behavioral evaluation the brain areas prefrontal cortex (PFC), hippocampus and amygdala were collected. AMPH induced hyperlocomotion, risk-taking behavior and multiple cognitive deficits which resemble mania. LIRA reversed AMPH-induced hyperlocomotion, working and recognition memory impairments, while Li + LIRA240 rescued all behavioral changes induced by AMPH. LIRA reversed AMPH-induced hippocampal oxidative and neurotrophic changes. Li + LIRA240 augmented Li antioxidant effects and greatly reversed AMPH-induced BDNF changes in PFC and hippocampus. LIRA rescued the weight gain induced by Li in the course of mania model. Therefore, LIRA can reverse some mania-like behavioral alterations and combined with Li augmented the mood stabilizing and neuroprotective properties of Li. This study points to LIRA as a promising adjunctive tool for BD treatment and provides the first rationale for the design of clinical trials investigating its possible antimanic effect.

Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study.

Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis. The intensity and distribution of these histopathological findings over the Cornu Ammonis (CA) subfields are important for the classification of HS and prognostication of patients with temporal lobe epilepsy (TLE). Several studies have associated the neuronal density reduction in the hippocampus with cognitive decline in patients with TLE. The current study aimed at investigating whether the expression of glial proteins in sclerotic hippocampi is associated with presurgical memory performance of patients with TLE. Before amygdalohippocampectomy, patients were submitted to memory tests. Immunohistochemical and morphometric analyses with glial fibrillary acidic protein (GFAP) for astrogliosis and human leucocyte antigen DR (HLA-DR) for microgliosis were performed in paraffin-embedded HS and control hippocampi. Sclerotic hippocampi exhibited increased gliosis in comparison with controls. In patients with TLE, the area and intensity of staining for HLA-DR were associated with worse performance in the memory tests. Glial fibrillary acidic protein was neither associated nor correlated with memory test performance. Our data suggest association between microgliosis, but not astrogliosis, with visual memory decline in patients with TLE.

Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy.

Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants. AIMS: The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance. MAIN METHODS: Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction. KEY FINDINGS: Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement. SIGNIFICANCE: Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.

Efficacy of the Spanish modified Story Memory Technique in Mexicans with multiple sclerosis: A pilot randomized controlled trial.

BACKGROUND: Memory impairments commonly afflict individuals with MS. While evidence-based cognitive rehabilitation treatments are available in English, the lack of such interventions in Spanish is an important barrier to care for Hispanics with MS. There is class I evidence that the modified Story Memory Technique (mSMT) improves learning in English. This intervention has been translated and adapted into Spanish. OBJECTIVE: To examine the preliminary efficacy of the Spanish mSMT to improve learning in Mexicans with MS. METHODS: Twenty individuals with relapsing-remitting MS were randomized to treatment (n = 10) or placebo control (n = 10) groups. The Spanish mSMT is a 10-session intervention that teaches imagery and context to facilitate learning. The control condition was matched to the treatment condition in treatment duration, and stimulus content and presentation. Participants completed baseline and post-treatment neuropsychological assessments. RESULTS: Individuals who received the Spanish mSMT showed significant improvements in learning and life satisfaction relative to the control group. Also observed were a near-moderate effect size on perceived memory complaints and a moderate-to-large effect size on the family's perception of the patient's competency. CONCLUSIONS: The Spanish mSMT showed preliminary efficacy in improving learning deficits in Mexicans with MS, and such improvements may extend to other domains.

The impact of intensive care unit diaries on patients' and relatives' outcomes: a systematic review and meta-analysis.

BACKGROUND: Memory gaps in intensive care unit (ICU) survivors are associated with psychiatric disorders. The ICU diaries improve the patient's factual memory of the ICU, but it is not clear if they reduce the incidence of psychiatric disorders in patients and relatives after hospital discharge. The aim of this study is to evaluate the literature on the effect of ICU diaries for patients admitted in ICU and their relatives. METHODS: Two authors independently searched the online databases PubMed, OVID, Embase, EBSCO host, and PsycINFO from inception to July 2019. Studies were included if the intervention group (ICU diary) was compared with a group with no diaries and the sample was comprised patients ≥ 18 years old admitted in the ICU for more than 24 h and their relatives. Randomized clinical trials, observational studies, letter with original data, and abstracts were included, irrespective of the language. The search was not limited by any specific outcome. Review articles, commentaries, editorials, and studies without a control group were excluded. Structured tools were used to assess the methodological quality ("Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I)" for cohort studies and the "Cochrane Risk of Bias tool" for included RCTs and before/after studies). A random-effects model was employed considering the anticipated variability between the studies. RESULTS: Seven hundred eighty-five titles were identified for screening. Two additional studies were selected after a reference search, and after a full-text review, a total of 12 studies were included. When pooling the results, ICU diary was associated with lower risk of depression (RR 0.41, 95% CI 0.23-0.75) and better quality of life (10.3 points higher in SF-36 general health score, 95% CI 0.79-19.8), without a decrease in anxiety or post-traumatic stress disorder (PTSD). For the relatives receiving an ICU diary, there was no difference in the incidence of PTSD, anxiety, or depression. CONCLUSION AND RELEVANCE: This systematic review and meta-analysis supports the use of ICU diaries to reduce the risk of depression and preserve the quality of life of patients after ICU admission. ICU diaries do not seem to have any beneficial effect on the relatives of the patients. TRIAL REGISTRATION: PROSPERO, CRD42019136639.

Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment.

Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients. Graphical Abstract Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.

Depression, anxiety-like behavior, and memory impairment in mice exposed to chitosan-coated zein nanoparticles.

The advent of biotechnology provided the synthesis of nanoproducts with diverse applications in the field of medicine, agriculture, food, among others. However, the toxicity of many nanoparticles (NP) currently used, which can penetrate natural systems and impact organisms, is not known. Thus, in this study, we evaluated whether the short exposure (5 days) to low concentrations of chitosan-coated zein nanoparticles (ZNP-CS) (0.2 ng/kg, 40 ng/kg, and 400.00 ng/kg) was capable of causing behavioral alterations compatible with cognitive deficit, as well as anxiety and depression-like behavior in Swiss mice. However, we observed an anxiogenic effect in the animals exposed to the highest ZNP-CS concentration (400.00 ng/kg), without locomotor alterations suggestive of sedation or hyperactivity in the elevated plus maze (EPM) test. We also observed that the ZNP-CS caused depressive-like behavior, indicated by the longer immobile time in the tail suspension test and the animals exposed to ZNP-CS presented deficit in recognition of the new object, not related to locomotor alteration in this test. To the best of our knowledge, this is the first report of the neurotoxicity of ZNP in a mammal animal model, contributing to the biological safety assessment of these nanocomposites.

The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.

Huntington's Disease (HD) is an autosomal-dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5-positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In this study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory. Our results demonstrate that subchronic treatment with the mGluR5 PAM VU0409551 was effective in reversing the memory deficits exhibited by BACHD mice, a mouse model for HD. Moreover, VU0409551 treatment stabilized mGluR5 at the cellular plasma membrane of BACHD mice, increasing the expression of several genes important for synaptic plasticity, including c-Fos, brain-derived neurotrophic factor, Arc/Arg3.1, syntaxin 1A, and post-synaptic density-95. In addition, VU0409551 treatment also increased dendritic spine density and maturation and augmented the number of pre-synaptic sites. In conclusion, our results demonstrate that VU0409551 triggered the activation of cell signaling pathways important for synaptic plasticity, enhancing the level of dendritic spine maturation and rescuing BACHD memory impairment. OPEN PRACTICES: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in amyloid beta neurotoxicity.

Recently, nongenetic animal models to study the onset and development of Alzheimer's disease (AD) have appeared, such as the intrahippocampal infusion of peptides present in Alzheimer amyloid plaques [i.e., amyloid-ß (Aß)]. Nonpharmacological approaches to AD treatment also have been advanced recently, which involve combinations of behavioral interventions whose specific effects are often difficult to determine. Here we isolate the neuroprotective effects of three of these interventions-environmental enrichment (EE), anaerobic physical exercise (AnPE), and social enrichment (SE)-on Aß-induced oxidative stress and on impairments in learning and memory induced by Aß. Wistar rats were submitted to 8 wk of EE, AnPE, or SE, followed by Aß infusion in the dorsal hippocampus. Short-term memory (STM) and long-term memory (LTM) of object recognition (OR) and social recognition (SR) were evaluated. Biochemical assays determined hippocampal oxidative status: reactive oxygen species, lipid peroxidation by thiobarbituric acid reactive substance (TBARS) test, and total antioxidant capacity by ferric reducing/antioxidant power (FRAP), as well as acetylcholinesterase activity. Aß infusion resulted in memory deficits and hippocampal oxidative damage. EE and AnPE prevented all memory deficits (STM and LTM of OR and SR) and lipid peroxidation (i.e., TBARS). SE prevented only the SR memory deficits and the decrease of total antioxidant capacity decrease (i.e., FRAP). Traditionally, findings obtained with EE protocols do not allow discrimination of the roles of the three individual factors involved. Here we demonstrate that EE and physical exercise have better neuroprotective effects than SE in memory deficits related to Aß neurotoxicity in the AD model tested.

Lithium prevents scopolamine-induced memory impairment in zebrafish.

We examined whether lithium carbonate (Li2CO3, 100mg/L) is able to prevent memory impairment induced by scopolamine. Moreover, we evaluated the effects of lithium on anxiety-like behavior and acetylcholinesterase activity in adult zebrafish. We demonstrated that lithium prevents the memory impairment induced by scopolamine, decreases exploration and increases the activity of acetylcholinesterase in zebrafish. Collectively, this contributes to a better understanding of the pharmacology of lithium, its interaction with cholinergic neurotransmission, and its possible application to therapeutic treatments aimed at improving cognition.

Relation between acetylcholinesterase and Na+, K+-ATPase activities with impaired memory of mice experimentally infected by Trypanosoma cruzi.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na+, K+-ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na+, K+-ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na+, K+-ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na+, K+-ATPase activities may be considered a mechanism involved in disease pathogenesis.

Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe)2, an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe)2 on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe)2 (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [3H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [3H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe)2 reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe)2 treatment was effective against these alterations.