Smoking Progression and Nicotine-Enhanced Reward Sensitivity Predicted by Resting-State Functional Connectivity in Salience and Executive Control Networks.

Introduction: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity (NERS) and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC.) during smoking abstinence predicts NERS and smoking progression in young light smokers.

Symbol relations training improves cognitive functioning in students with neurodevelopmental disorders.

Students with neurodevelopmental disorders [Specific Learning Disorders (SLD), Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD)] often experience learning challenges due to underlying weaknesses in cognitive processes. As these are some of the most common conditions to impact functioning, the development of effective treatments is a priority for neuropsychologists. However, the task of designing effective cognitive interventions has proven one of the most difficult challenges for our field.

APOE genotype influences P3b amplitude and response to smoking abstinence in young adults.

Rationale: There is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices.

Objective: We sought to determine whether young female carriers of the APOE ε4 allele, relative to noncarriers, would exhibit larger abstinence-induced decreases in P3b amplitude during a two-stimulus auditory oddball task.

Butein attenuates the cytotoxic effects of LPS-stimulated microglia on the SH-SY5Y neuronal cell line.

Neuroinflammation is involved in brain aging and neuronal cell death in neurodegenerative diseases such as Alzheimer's disease (AD). Butein has been suggested to have anti-inflammatory, anti-apoptotic, and anti-cancer effects. However, few studies have been done to evaluate whether butein exerts protective effects on neurons, and the potential mechanism for this effect has not been studied.

Impaired memory and marble burying activity in deformed epidermal autoregulatory factor 1 (Deaf1) conditional knockout mice.

Deleterious mutations within the DNA binding domain of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of neurodevelopmental disorders including intellectual disabilities and autism spectrum disorders. While whole animal deletion of Deaf1 in mice is lethal, mice with conditional disruption of the gene in neuronal precursor cells can display memory deficits and increased anxiety-like behavior. This study aimed to further characterize learning and memory alterations and assess changes in marble burying activity and hippocampal size in mice with conditional deletion of Deaf1.

Impaired Glucose Tolerance and Reduced Plasma Insulin Precede Decreased AKT Phosphorylation and GLUT3 Translocation in the Hippocampus of Old 3xTg-AD Mice.

Several studies have demonstrated that mouse models of Alzheimer's disease (AD) can exhibit impaired peripheral glucose tolerance. Further, in the APP/PS1 mouse model, this is observed prior to the appearance of AD-related neuropathology (e.g.

Evidence for altered insulin receptor signaling in Alzheimer's disease.

Epidemiological data have shown that metabolic disease can increase the propensity for developing cognitive decline and dementia, particularly Alzheimer's disease (AD). While this interaction is not completely understood, clinical studies suggest that both hyper- and hypoinsulinemia are associated with an increased risk for developing AD. Indeed, insulin signaling is altered in post-mortem brain tissue from AD patients and treatments known to enhance insulin signaling can improve cognitive function.

Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggests that both type 1 and type 2 diabetes are risk factors for AD-related dementia and several clinical studies have demonstrated that AD patients show alterations in peripheral glucose regulation characterized by insulin resistance (hyperinsulinemia) or hypoinsulinemia. Whether animal models of AD exhibit a pre-diabetic phenotype without additional dietary or experimental manipulation is unclear however, with contradictory data available.

Sex Differences in Long-Term Potentiation at Temporoammonic-CA1 Synapses: Potential Implications for Memory Consolidation.

Sex differences in spatial memory have long been observed in humans, non-human primates and rodents, but the underlying cellular and molecular mechanisms responsible for these differences remain obscure. In the present study we found that adolescent male rats outperformed female rats in 7 d and 28 d retention probes, but not in learning trials and immediate probes, in the Morris water maze task. Male rats also had larger long-term potentiation (LTP) at hippocampal temproammonic-CA1 (TA-CA1) synapses, which have been implicated to play a key role in place field and memory consolidation, when protocols designed to elicit late-stage LTP (LLTP) were used.

The essential role of hippocampal alpha6 subunit-containing GABAA receptors in maternal separation stress-induced adolescent depressive behaviors.

Exposure to early stressful adverse life events such as maternal separation severely impacts the development of the nervous system. Using immunohistochemistry, quantitative PCR and Western blot approaches, we found that alpha6 subunit-containing GABAA receptors (Gabra6-containing GABAA Rs) were expressed on hippocampal interneurons of adolescent rats. Maternal separation stress (MS) from postnatal day 2 to15 significantly reduced Gabra6 expression and provoked depressive behaviors such as anhedonia.

Experimentally induced diabetes worsens neuropathology, but not learning and memory, in middle aged 3xTg mice.

Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The cause of the disease is still unknown, but amyloid plaques and neurofibrillary tangles in the brain are thought to play a role. However, transgenic mouse models expressing these neuropathological features do not show severe or consistent cognitive impairments.

Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems.

Altered network timing in the CA3-CA1 circuit of hippocampal slices from aged mice.

Network patterns are believed to provide unique temporal contexts for coordinating neuronal activity within and across different regions of the brain. Some of the characteristics of network patterns modeled in vitro are altered in the CA3 or CA1 subregions of hippocampal slices from aged mice. CA3-CA1 network interactions have not been examined previously.

γ-secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Aβ.

Deposition of β -amyloid (Aβ) peptides, cleavage products of β-amyloid precursor protein (APP) by β-secretase-1 (BACE1) and γ-secretase, is a neuropathological hallmark of Alzheimer's disease (AD). γ-Secretase inhibition is a therapeutical anti-Aβ approach, although changes in the enzyme's activity in AD brain are unclear. Cerebrospinal fluid (CSF) Aβ peptides are thought to derive from brain parenchyma and thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Aβ efficacy.

Water maze testing to identify compounds for cognitive enhancement.

The water maze task is widely used to evaluate spatial learning and memory in rodents. The basic paradigm requires an animal to swim in a pool until it finds a hidden escape platform. The animals learn to find the platform using extra-maze cues and, after several training trials, are able to swim directly to it from any starting location.

Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3×Tg-AD mice.

The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of growing interest. Senile plaques and tauopathy are found in epileptic human temporal lobe structures, and individuals with AD have an increased incidence of spontaneous seizures. However, why and how epilepsy is associated with enhanced AD-like pathology remains unknown.

Chronic haloperidol-induced spatial memory deficits accompany the upregulation of D(1) and D(2) receptors in the caudate putamen of C57BL/6 mouse.

Aims: Haloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D(2), but low affinities to D(1) receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D(1) and D(2) receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D(1) and D(2) receptors in specific brain regions, with the hypothesis that the D(1) and D(2) receptors in CP are important players in spatial memory function of the brain.

Age-related intraneuronal elevation of αII-spectrin breakdown product SBDP120 in rodent forebrain accelerates in 3×Tg-AD mice.

Spectrins line the intracellular surface of plasmalemma and play a critical role in supporting cytoskeletal stability and flexibility. Spectrins can be proteolytically degraded by calpains and caspases, yielding breakdown products (SBDPs) of various molecular sizes, with SBDP120 being largely derived from caspase-3 cleavage. SBDPs are putative biomarkers for traumatic brain injury.

Electrical and Pharmacological Stimuli Reveal a Greater Susceptibility for CA3 Network Excitability in Hippocampal Slices from Aged vs. Adult Fischer 344 Rats.

Clinical data and experimental studies in rats have shown that the aged CNS is more susceptible to the proconvulsive effects of the excitotoxic glutamate analogues kainate (KA) and domoate (DA), which bind high-affinity receptors localized at mossy fiber (MF) synapses in the CA3 subregion of the hippocampus. Although decreased renal clearance appears to play a role in the hypersensitivity of the aged hippocampus to systemically-administered DA, it is unclear if the excitability of the CA3 network is also altered with age. Therefore, this study monitored CA3 field potential activity in hippocampal slices from aged and adult male Fischer 344 rats in response to electrical and pharmacological network stimulation targeted to the MF-CA3 circuit.

BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice.

The brain is capable of remarkable synaptic reorganization following stress and injury, often using the same molecular machinery that governs neurodevelopment. This form of plasticity is crucial for restoring and maintaining network function. However, neurodegeneration and subsequent reorganization can also play a role in disease pathogenesis, as is seen in temporal lobe epilepsy and Alzheimer's disease.

Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: effects of antipsychotic drugs.

Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator)-fed C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for 5 weeks then returned to normal food for 3 weeks, during which period mice were treated with different antipsychotic drugs.

BACE1 elevation is involved in amyloid plaque development in the triple transgenic model of Alzheimer's disease: differential Aβ antibody labeling of early-onset axon terminal pathology.

β-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. β-Amyloid (Aβ) deposition can manifest as compact and diffuse plaques; it is unclear why the same Aβ molecules aggregate in different patterns.

Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats.

Although expression of some genes is known to change during neuronal activity or plasticity, the overall relationship of gene expression changes to memory or memory disorders is not well understood. Here, we combined extensive statistical microarray analyses with behavioral testing to comprehensively identify genes and pathways associated with aging and cognitive dysfunction. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups based on their Morris water maze performance relative to young-adult (Y) animals.