Memory Defects Research Articles

Effect of Cognitive-emotional Rehabilitation on Cognitive Function and Memory of Patients With Traumatic Brain Injury

Background and Aims Today, traumatic brain injury and defects in cognitive functions and memory are the most frequent problems after brain injury. This study aims to examine the effectiveness of emotional and cognitive rehabilitation on cognitive performance and memory in patients with traumatized brain injury. Methods This study is an applied study in terms of purpose and experimental in terms of collecting information method. Considering purposive sampling and random selection of samples, we used the randomized block experiment with a pre-test-post-test design with a control group. We used the emotional cognitive rehabilitation protocol based on Gross model (2002) and Nejati cognitive rehabilitation to train emotional and cognitive rehabilitation (2017). The study's statistical population included all brain-injured patients with cognitive defects and memory problems referred to Neurology Clinic, Shahid Motahari Hospital, and Razmehr Psychiatric Clinic, Shiraz City, Iran, from June 22, 2019, to January 20, 2020. This study consisted of 3 groups (2 experimental and 1 control group) at three levels (mild, moderate, and severe patients). The study participants were 45 patients selected after a brief mental examination with a mini-mental state examination test. Results Cognitive rehabilitation significantly (P<0.001) increased the brain-injured patients' cognitive performance. Also, emotional and cognitive rehabilitation significantly (P<0.001) affected the brain-injured patients' cognitive performance. Finally, cognitive rehabilitation significantly (P<0.001) increased the brain-injured patients' memory performance. Conclusion It seems that through delivering necessary training and education regarding effective interpersonal skills, computer drills, practices at home, and so on, emotional and cognitive rehabilitation helps the brain injured people to properly manage emotions, effectively establish interpersonal communication, and lighten the load of negative emotions, and consequently memory gets improved will less stress. In fact, emotional and cognitive rehabilitation is a complete collection of training for regulating emotions and enhancing and growing memory. Thus, emotional and cognitive rehabilitation's significant effect on memory enhancement is logical and acceptable. In conclusion, this protocol effectively improves brain-injured people's cognitive performance.

P85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease

BackgroundRibosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown.MethodsWe fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice.Resultsp85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice.ConclusionsThese results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.

Evaluation of the Negative Effects of Opium Tincture on Memory and Hippocampal Neurons in the Presence of Chicory Extract.

Due to the high prevalence of addiction in society and the need to its attention, various methods are used for addiction withdrawal. The side effects of some methods restrict their use and increase the risk of recurrence. One of the Iranian useful methods is consumption of opium tincture (OT) that may cause brain structure and memory defects. Hence, this study aimed the effects of different doses of OT on memory and hippocampal neurons with the use of an antioxidant such as various concentrations chicory. In the present study, 70 Wistar rats were randomly divided into 10 groups and the effect of various doses of chicory extract and OT were assessed on memory by the passive avoidance test. The neurons and astrocyte cells numbers in dentate gyrus were investigated, using histological examination. In passive avoidance test, the total time in dark compartment was significantly more in groups with 100 and 75 μl OT compared with control and normal saline groups (P < 0.001). Traffic number results showed that there was a significant difference between T100 and control groups (P > 0.05). Moreover, initial latency time was significantly shorter in groups with 75 and 100 μl of OT compared with control and normal saline groups (P < 0.05). However, the presence 250 mg/kg of chicory increases granular layer thickness of dentate gyrus and number of neurons. The use of 250 mg/kg of chicory extract may be promising strategy for inducing neurogenesis and this dose could prevent neural damage.

Psychopathological intersection of OCD and PTSD: scoping review of similitudes and differences.

Although Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder have distinct diagnostic criteria, some psychopathological phenomena seem to be shared, what may lead to misdiagnosis and to wrong therapeutical decisions. This scoping review explores the psychopathological similitudes and differences of both disorders. It followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and included articles published in Portuguese, English or Spanish in the last 50 years in the PubMed database. Case-reports were excluded. Fifty-three studies with different designs were included (30(56.5%) were cross-sectional; 8 (15.1%) were case control; 1 (1.9%) was cohort; 3 (5.7%) were clinical trials; 9 (17.0%) were reviews/systematic reviews; and 2 (3.8%) were meta-analysis.). The main described interfaced psychopathological aspects by the included studies were flashbacks x obsessions; avoidant behavior; depressive, anxious, and somatic symptoms; sexuality, sleep, and appetite; psychiatric comorbidities; and suicidality. The intersection of clinical features seems to be on the extrinsic psychopathological dimension. The psychopathological symptoms core (intrinsic characteristics) is distinctly different, since flashbacks and obsessions are consequences of predominant diverse defective mental function: the former from memory, the last from thought. In the same way, the avoidant behaviors are derived from different purposes and inner necessities.

Evaluation the Effect of Crocin on Bisphenol A-Induced Memory Impairment in Rats: Role of ERK, CaMKII, and CREB Proteins in Hippocampus

Introduction: Bisphenol A (BPA) is a toxic chemical that is used as a monomer in the production of plastic products. The BPA has an endocrine-disrupting effect and ‎induces damage to the nervous system. Crocin, an active ingredient of Crocus sativus L. has ‎neuroprotective effects. Therefore, this study aimed to evaluate crocin’s effects on BPA-induced ‎memory impairment in rats and the levels of Extracellular Signal-Regulated Kinases (ERK), Ca2+/Calmodulin-Dependent Protein Kinase-II (CaMKII), and Cyclic AMP-Response Element-Binding Protein (CREB) proteins in the hippocampus. Method: Bisphenol A (100 mg/kg, gavage) and crocin (10, 20, and 40 mg/kg, IP) were administered to adult male rats for 28 days. Memory and learning functions were evaluated by the Morris water maze, and the level of proteins was determined using the Western blot method. Results: Administration of the BPA (100 mg/kg) significantly induced memory impairment and reduced the levels of ERK, p.ERK, CaMKII, and p.CREB proteins in the BPA group, compared to the control group. On the other hand, crocin (20 mg/kg) markedly improved learning and memory impairment and increased the levels of ERK, p.ERK, and CaMKII proteins in the hippocampus, compared to the BPA (100 mg/kg) group. Conclusion: Administration of crocin (20 mg/kg) improves memory and learning defects induced by BPA (100 mg/kg). The enhancement of the ‎p.ERK, ERK, and p. CaMKII protein levels in the hippocampus has an important role in crocin protective effects

Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring

Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 μg/m3) and (2.78 ± 1.19 μg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p < 0.05), suggesting spatial memory impairments. The acquisition trials of Morris Water Maze did not show a significant difference in learning ability between the groups. The mRNA level of interleukin 6 (IL-6) in the CAP group hippocampus (10.80 ± 7.03) increased significantly compared to the FA group (1.08 ± 0.43). Interestingly, the methylation levels of the CpG sites in the IL-6 promoter region declined significantly in the CAP group, (5.66 ± 0.83)% vs. (4.79 ± 0.48)%. Prenatal exposure to concentrated ambient PM2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.

Ameliorative effects of omega-lycotoxin-Gsp2671e purified from the spider venom of Lycosa praegrandis on memory deficits of glutamate-induced excitotoxicity rat model.

Memory impairment is one of the main complications of Alzheimer's disease (AD). This condition can be induced by hyper-stimulation of N-Methyl-D-aspartate receptors (NMDARs) of glutamate in the hippocampus, which ends up to pyramidal neurons determination. The release of neurotransmitters relies on voltage-gated calcium channels (VGCCs) such as P/Q-types. Omega-lycotoxin-Gsp2671e (OLG1e) is a P/Q-type VGCC modulator with high affinity and selectivity. This bio-active small protein was purified and identified from the Lycosa praegrandis venom. The effect of this state-dependent low molecular weight P/Q-type calcium modulator on rats was investigated via glutamate-induced excitotoxicity by N-Methyl-D-aspartate. Also, Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input-output and Long-term potentiation (LTP) curves were recorded in mossy fiber and the amount of synaptophysin (SYN), synaptosomal-associated protein, 25kDa (SNAP-25), and synaptotagmin 1(SYT1) genes expression were measured using Real-time PCR technique for synaptic quantification. The outcomes of the current study suggest that OLG1e as a P/Q-type VGCC modulator has an ameliorative effect on excitotoxicity-induced memory defects and prevents the impairment of pyramidal neurons in the rat hippocampus.

Immune system modulation in aging: Molecular mechanisms and therapeutic targets.

The function of the immune system declines during aging, compromising its response against pathogens, a phenomenon termed as "immunosenescence." Alterations of the immune system undergone by aged individuals include thymic involution, defective memory T cells, impaired activation of naïve T cells, and weak memory response. Age-linked alterations of the innate immunity comprise perturbed chemotactic, phagocytic, and natural killing functions, as well as impaired antigen presentation. Overall, these alterations result in chronic low-grade inflammation (inflammaging) that negatively impacts health of elderly people. In this review, we address the most relevant molecules and mechanisms that regulate the relationship between immunosenescence and inflammaging and provide an updated description of the therapeutic strategies aimed to improve immunity in aged individuals.

Targeting mGlu1 Receptors in the Treatment of Motor and Cognitive Dysfunctions in Mice Modeling Type 1 Spinocerebellar Ataxia

Type 1 spinocerebellar ataxia (SCA1) is a progressive neurodegenerative disorder with no effective treatment to date. Using mice modeling SCA1, it has been demonstrated that a drug that amplifies mGlu1 receptor activation (mGlu1 receptor PAM, Ro0711401) improves motor coordination without the development of tolerance when cerebellar dysfunction manifests (i.e., in 30-week-old heterozygous ataxin-1 [154Q/2Q] transgenic mice). SCA1 is also associated with cognitive dysfunction, which may precede cerebellar motor signs. Here, we report that otherwise healthy, 8-week-old SCA1 mice showed a defect in spatial learning and memory associated with reduced protein levels of mGlu1α receptors, the GluN2B subunit of NMDA receptors, and cannabinoid CB1 receptors in the hippocampus. Systemic treatment with Ro0711401 (10 mg/kg, s.c.) partially corrected the learning deficit in the Morris water maze and restored memory retention in the SCA1 mice model. This treatment also enhanced hippocampal levels of the endocannabinoid, anandamide, without changing the levels of 2-arachidonylglycerol. These findings suggest that mGlu1 receptor PAMs may be beneficial in the treatment of motor and nonmotor signs associated with SCA1 and encourage further studies in animal models of SCA1 and other types of SCAs.

Lowering Synaptogyrin‐3 Expression Rescues Tau‐Induced Memory Deficits and Synaptic Loss in the Presence of Microglial Activation

AbstractBackgroundTau is implicated in multiple neurodegenerative disorders, including Alzheimer’s disease. Synaptic loss and neuroinflammation are characteristic feautures of tauopathies, but it is unclear if these pathological events are causally linked and whether they are relevant for cognitive decline. Mutations and/or hyperphosphorylation of Tau leads its accumulation at synapses, where Tau binds to synaptic vesicle‐associated protein Synaptogyrin‐3 resulting in clustering of vesicles and impaired synaptic function. Given that Synaptogyrin‐3 is uniquely present at pre‐synaptic terminals, this allows us to decipher the contribution of pre‐synaptic Tau to overall Tau‐induced pathology.MethodWe generated a synaptogyrin‐3 knockout mouse line using CRISPR‐Cas9 technology. Synaptogyrin‐3−/− and +/− mice are viable and fertile and do not show overt phenotypes. We bred synaptogyrin‐3+/− mice with human Tau P301S‐expressing mice (PS19 line) and aged the offspring. We used several techniques, including electrophysiology, behavioral tests, immunohistochemistry and electron microscopy, to determine the effects of lowering Synaptogyrin‐3 expression in a tauopathy mouse model.ResultWe found that heterozygous knockout of Synaptogyrin‐3 in Tau P301S mice was sufficient to rescue synaptic plasticity and working memory defects. Moreover, lowering Synaptogyrin‐3 expression prevented synaptic degeneration and loss of synaptic markers in Tau P301S mice. Interestingly, proliferation and activation of astrocytes and microglia are observed in Tau P301S; synaptogyrin‐3+/− mice to the same extent as in their Tau P301S littermates.ConclusionOur results indicate that Tau induces synaptic loss and neuroinflammation independently, and that neuroinflammation is not sufficient to cause synaptic loss. In addition, pre‐synaptic defects caused by Tau are enough to drive defects in working memory.

Researches on cognitive sequelae of burn injury: Current status and advances.

Burn injury is a devastating disease with high incidence of disability and mortality. The cognitive dysfunctions, such as memory defect, are the main neurological sequelae influencing the life quality of burn-injured patients. The post-burn cognitive dysfunctions are related to the primary peripheral factors and the secondary cerebral inflammation, resulting in the destruction of blood-brain barrier (BBB), as is shown on Computed Tomography (CT) and magnetic resonance imaging examinations. As part of the neurovascular unit, BBB is vital to the nutrition and homeostasis of the central nervous system (CNS) and undergoes myriad alterations after burn injury, causing post-burn cognitive defects. The diagnosis and treatment of cognitive dysfunctions as burn injury sequelae are of great importance. In this review, we address the major manifestations and interventions of post-burn cognitive defects, as well as the mechanisms involved in memory defect, including neuroinflammation, destruction of BBB, and hormone imbalance.

The induction of ferroptosis in posthemorrhagic hydrocephalus

Posthemorrhagic hydrocephalus (PHH) is a common neurological disease characterized by the disordered secretion of cerebrospinal fluid from the choroid plexus, ventricular dilation, and increased intracranial pressure after hemorrhage. Although these pathological processes are well established, the effective biomarkers for the diagnosis of PHH are still limited, largely because the underlying mechanisms—including cell death in the choroid plexus—are not well defined. Ferroptosis, a newly recognized type of programmed cell death, has been found to play a key role in a variety of pathologic conditions and diseases, including Parkinson’s and Alzheimer’s diseases. However, whether ferroptosis is induced in PHH is still unknown. In the current study, a rat model of PHH was established to investigate the induction of ferroptosis in PHH. Along with defects in memory and cognition, we observed that rats with experimentally induced PHH also demonstrated lipid peroxidation (a key marker of ferroptosis), as well as a significant increase and a significant decrease in two ferroptosis-specific genes, ACSL4 and SLC7A11, respectively. Thus, ferroptosis may serve as an auxiliary indicator for the diagnosis of PHH.

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study.

Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The 'nootropic-like' activity could be related to diminished AChE and neuroinflammatory mediator levels.

ETHNO PRACTICE IN BHUTONMADA: A REVIEW

Bhutonmada/Grahonmada is a Psychiatric condition characterized by abnormal behaviour in terms of an exhibition of strength, energy, valour and enthusiasm, defects in perception, retention and memory, abnormality of speech, and abnormality in perceiving self and environment. Bhutavidya deals with the possession of demons or evil spirits and their management. It is widely practised in many parts of India; however, Ethno-practitioners in some regions of Kerala and Karnataka who have proficient knowledge about Bhutavidya are treating patients successfully. A combined approach of Jyotishyashastra, and Daivavyapashraya, like Mantra-Homa-Bali and Bheshaja, are followed by such practitioners. In this approach, Jyothishyashastra is used as a tool for diagnosis, while a combined approach of Daivavyapashraya and Yuktivyapashraya is used in its treatment. This article presents the concept of Bhutavidya explained in Ayurveda along with descriptions of Ethno-practices narrated by a Bhutavaidya residing in Kasargod district of Kerala; information collected through an in-depth, focused Interview.

Cd1 Mutation in Drosophila Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory.

Being involved in development of Huntington’s, Parkinson’s and Alzheimer’s diseases, kynurenine pathway (KP) of tryptophan metabolism plays a significant role in modulation of neuropathology. Accumulation of a prooxidant 3-hydroxykynurenine (3-HOK) leads to oxidative stress and neuronal cell apoptosis. Drosophila mutant cardinal (cd1) with 3-HOK excess shows age-dependent neurodegeneration and short-term memory impairments, thereby presenting a model for senile dementia. Although cd gene for phenoxazinone synthase (PHS) catalyzing 3-HOK dimerization has been presumed to harbor the cd1 mutation, its molecular nature remained obscure. Using next generation sequencing, we have shown that the cd gene in cd1 carries a long deletion leading to PHS active site destruction. Contrary to the wild type Canton-S (CS), cd1 males showed defective long-term memory (LTM) in conditioned courtship suppression paradigm (CCSP) at days 5–29 after eclosion. The number of dopaminergic neurons (DAN) regulating fly locomotor activity showed an age-dependent tendency to decrease in cd1 relative to CS. Thus, in accordance with the concept “from the gene to behavior” proclaimed by S. Benzer, we have shown that the aberrant PHS sequence in cd1 provokes drastic LTM impairments and DAN alterations.

Vitamin B12 administration prevents ethanol-induced learning and memory impairment through re-establishment of the brain oxidant/antioxidant balance, enhancement of BDNF and suppression of GFAP

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.

Increased KIF11/kinesin-5 expression offsets Alzheimer Aβ-mediated toxicity and cognitive dysfunction

SummaryPreviously, we found that amyloid-beta (Aβ) competitively inhibits the kinesin motor protein KIF11 (Kinesin-5/Eg5), leading to defects in the microtubule network and in neurotransmitter and neurotrophin receptor localization and function. These biochemical and cell biological mechanisms for Aβ-induced neuronal dysfunction may underlie learning and memory defects in Alzheimer’s disease (AD). Here, we show that KIF11 overexpression rescues Aβ-mediated decreases in dendritic spine density in cultured neurons and in long-term potentiation in hippocampal slices. Furthermore, Kif11 overexpression from a transgene prevented spatial learning deficits in the 5xFAD mouse model of AD. Finally, increased KIF11 expression in neuritic plaque-positive AD patients’ brains was associated with better cognitive performance and higher expression of synaptic protein mRNAs. Taken together, these mechanistic biochemical, cell biological, electrophysiological, animal model, and human data identify KIF11 as a key target of Aβ-mediated toxicity in AD, which damages synaptic structures and functions critical for learning and memory in AD.

Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype.

CHAMP1 is a gene associated with intellectual disability, which was originally identified as being involved in the maintenance of kinetochore–microtubule attachment. To explore the neuronal defects caused by CHAMP1 deficiency, we established mice that lack CHAMP1. Mice that are homozygous knockout for CHAMP1 were slightly smaller than wild-type mice and died soon after birth on pure C57BL/6J background. Although gross anatomical defects were not found in CHAMP1−/− mouse brains, mitotic cells were increased in the cerebral cortex. Neuronal differentiation was delayed in CHAMP1−/− neural stem cells in vitro, which was also suggested in vivo by CHAMP1 knockdown. In a behavioural test battery, adult CHAMP1 heterozygous knockout mice showed mild memory defects, altered social interaction, and depression-like behaviours. In transcriptomic analysis, genes related to neurotransmitter transport and neurodevelopmental disorder were downregulated in embryonic CHAMP1−/− brains. These results suggest that CHAMP1 plays a role in neuronal development, and CHAMP1-deficient mice resemble some aspects of individuals with CHAMP1 mutations.

Levetiracetam alleviates cognitive decline in Alzheimer's disease animal model by ameliorating the dysfunction of the neuronal network.

BackgroundPatients with Alzheimer’s disease (AD) have a significantly higher risk of seizures than other individuals in an age-matched population, suggesting a close association between epilepsy and AD. We aimed to examine the effects of levetiracetam (LEV)—a drug for treating seizures—on learning and memory and the neuropathological features of AD.MethodsWe crossbred APP23 mice with microtubule-associated protein tau (MAPT) transgenic mice to generate APP23/MAPT mice. These mice were treated with different concentrations of LEV in the presence of kainic acid (KA) for 3 months.ResultsLow doses of LEV alleviated the effects of KA on memory defects in APP23/MAPT mice. Mechanistic investigations showed that low concentrations of LEV decreased tau phosphorylation by reducing the activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3α/β, thus rescuing neurons from synaptic dystrophy and apoptosis. Low doses of LEV inhibited the effects of KA (i.e., inducing neuroinflammation and impairing the autophagy of amyloid β-peptide), thus improving cognitive decline. High concentrations of LEV decreased the production and deposition of amyloid β-peptide (Aβ) by reducing the expression of β-site APP-cleaving enzyme 1 and presenilin 1. However, high concentrations of LEV also induced neuronal apoptosis, decreased movement ability in mice, and did not alleviate cognitive decline in AD mice.ConclusionOur results support the hypothesis that aberrant network activity contributes to the synaptic and cognitive deficits in APP23/MAPT mice. A low concentration of LEV may help ameliorate abnormalities of AD; however, a high LEV concentration did not induce similar results.

Dlg Is Required for Short-Term Memory and Interacts with NMDAR in the Drosophila Brain.

The vertebrates’ scaffold proteins of the Dlg-MAGUK family are involved in the recruitment, clustering, and anchoring of glutamate receptors to the postsynaptic density, particularly the NMDA subtype glutamate-receptors (NRs), necessary for long-term memory and LTP. In Drosophila, the only gene of the subfamily generates two main products, dlgA, broadly expressed, and dlgS97, restricted to the nervous system. In the Drosophila brain, NRs are expressed in the adult brain and are involved in memory, however, the role of Dlg in these processes and its relationship with NRs has been scarcely explored. Here, we show that the dlg mutants display defects in short-term memory in the olfactory associative-learning paradigm. These defects are dependent on the presence of DlgS97 in the Mushroom Body (MB) synapses. Moreover, Dlg is immunoprecipitated with NRs in the adult brain. Dlg is also expressed in the larval neuromuscular junction (NMJ) pre and post-synaptically and is important for development and synaptic function, however, NR is absent in this synapse. Despite that, we found changes in the short-term plasticity paradigms in dlg mutant larval NMJ. Together our results show that larval NMJ and the adult brain relies on Dlg for short-term memory/plasticity, but the mechanisms differ in the two types of synapses.