Memory Deficiency Research Articles

Impairment of hippocampal neurogenesis in streptozotocin-treated diabetic rats

Adult neurogenesis in dentate gyrus (DG) is an evolutionarily preserved trait in most mammals examined thus far. Neuronal proliferation and subsequent integration of new neurons into the hippocampal circuit are regulated processes that can have profound effects on an animal's behaviour. A streptozotocin model of type I diabetes, characterized by low insulin and high plasma glucose levels, affects not only body's overall metabolism but also brain activity. Neurogenesis was measured within the DG of the hippocampus using immunohistochemical markers Ki67, Doublecortin, Calbindin (CaBP) and bromodeoxyuridine (BrdU). Cell proliferation, measured with the endogenous marker Ki67, was reduced by 45%, and cell survival, measured with BrdU, was reduced by 64% of the control. Combined effects on proliferation and survival produced dramatically lower neuronal production. Among the surviving cells only 33% matured normally as judged by the co-labelling of BrdU and CaBP. Such a reduction lowered the number of surviving cells with neuronal phenotype by over 80% of the control values and this is expected to cause a significant functional impairment of learning and memory in diabetic animals. These results may shed light on causes of diabetic neuropathology and provide an explanation for the memory deficiencies seen in some diabetic patients.

Recognition, recollection, familiarity and executive function in medicated patients with moderate Parkinson's disease

There is conflicting evidence about whether Parkinson's disease (PD) is associated with deficiencies in recognition memory (RM) and the processes which underlie it, namely recollection (a form of recall) and familiarity (a feeling of memory in the absence of recall). The aims of the current study were to examine forced-choice verbal RM (assessed with the Warrington Recognition memory Test), yes-no RM, recollection, familiarity and executive functioning in 17 patients with moderate PD and 17 healthy volunteers matched for age and premorbid intelligence. We predicted that patients with moderate PD would display a significant recollection deficit on the yes-no RM test, because their strategic memory processing that depends on executive functioning and is necessary for efficient encoding and/or retrieval, was disrupted. In contrast, familiarity memory, which is not dependent on these processes, and forced-choice RM (which is largely dependent on familiarity) should show higher levels of preservation. We also predicted that recollection should be correlated with severity of executive dysfunction. Our findings revealed that the PD patients were as likely to accurately discriminate between targets and distractors as the healthy volunteers on both RM tests. However, the PD patients were significantly less reliant on recollection-driven recognition decisions on the yes-no RM test when compared with the healthy control group. The patients also displayed executive function deficits, but these were not correlated with recollection. The extent to which the PD patients' reliance on familiarity at the expense of recollection is explained by impairments in strategic memory processes/executive function and/or medial temporal lobe retrieval processes needs further exploration.

Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring

Attention to addiction of women alone for fetus and infant's health has caused the possible role of father's status was less considered, while some developmental impairments including decrease of liter size, weight loss, congenital deficiencies, behavioral disorders, and learning and memory impairments in offspring with addicted father have been reported. In this study the effects of addiction of one or both parents to morphine on male and female offspring hippocampal long-term potentiation (LTP), were assessed.One hundred twenty female and 48 male rats (4–5 months, 250–270g) were used. Forty females and 16 males were addicted by oral administration of morphine (32mg/kg twice daily) for 5 days before mating. Then each two males with five females were housed (coupled) per cage as five groups for coupling: (A) addicted females+5% dextrose males (add.F); (B) addicted males+5% dextrose females (add.M); (C) addicted females+addicted males (add.MF); (D) 5% dextrose females+intact males (dex.F); (E) 5% dextrose males+intact females (dex.M). In puberty offspring LTP was induced in hippocampal dentate gyrus by stimulation of perforant path (pp). Changes of population spikes (PS) amplitude and LTP slope at 0, 5, 30, 60 and 120min were evaluated. Slope of LTP at 30, 60 and 120min, and amplitude of PS at 60 and 120min in add.F and add.M offspring were significantly lower than dextrose groups (P<0.01). LTP slope and PS amplitude of male and female offspring did not different between add.F and add.M groups. Our results suggest that both parental and paternal addiction to morphine may cause memory deficiency through reduction of LTP in hippocampus.

Adaptation, Intertextuality, and the Endless Deferral of Meaning

Adaptation, Intertextuality, and the Endless Deferral of Meaning

XV. Steroids

XV. Steroids

Calpain Cleaves a Memory Inhibitor

Calpain, a calcium-dependent protease, has been implicated in neuronal responses to various stimuli, and Shimizu et al . provide evidence that calpain contributes to certain types of learning and memory. Shimizu et al . (see commentary by Bolshakov) found that suprachiasmatic nucleus circadian oscillatory protein (SCOP) was abundant in the hippocampus of mice and rats. Overexpression of SCOP in cultured hippocampal neurons decreased the expression of an adenosine 3′,5′-monophosphate (cAMP) response element (CRE)-regulated reporter gene stimulated by brain-derived neurotrophic factor (BDNF), whereas knockdown of the endogenous protein using RNA interference enhanced reporter gene expression in the presence or absence of BDNF. CRE-mediated gene expression is downstream of activation of mitogen-activated protein kinases (MAPKs) and contributes to synaptic changes involved in learning and memory. SCOP was previously reported to inhibit K-Ras by sequestering the nucleotide-free form, thereby inhibiting MAPK activation. The authors found that SCOP abundance was decreased in cultured hippocampal neurons stimulated with BDNF, the glutamate receptor agonist NMDA, or KCl. Assays for SCOP cleavage in cell-free extracts in the presence of various protease pharmacological inhibitors indicated that calpains, not caspase 3 or the proteasome, cleaved SCOP and that SCOP cleavage required calcium. In cultured hippocampal neurons, calpain inhibition blocked SCOP degradation and decreased the phosphorylation (and activation) of the MAPK ERK-2 stimulated by BDNF. In mice, memory for new objects was associated with a decrease in the abundance of SCOP (in whole hippocampal extracts). Mice overexpressing SCOP using an inducible promoter showed decreased memory for new objects 24 hours after object training but no deficiency in short-term memory. Consistent with a role for calpain in memory, administration of a calpain inhibitor into the hippocampus blocked new object memory after 24 hours but had no effect on short-term memory measured after 8 minutes. K. Shimizu, T. Phan, I. M. Mansuy, D. R. Storm, Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory. Cell 128 , 1219-1229 (2007). [Online Journal] V. Y. Bolshakov, SCOPing out proteases in long-term memory. Cell 128 , 1029-1030 (2007). [Online Journal]

Four problems with psychodynamic assessment of drug abusers

The purpose of the present paper was to discuss problems in psychodynamic personality assessment of drug abusers diagnosed with personality disorders (PDs). Four problems related to interview assessments, such as SCID (Structured Clinical Interview for DSM) and KAPP (Karolinska Psychodynamic Profile) were discussed. The problems were: (1) the drug interferes with personality, (2) the duration of detoxification before drug abusers are tested and interviewed is usually insufficient, (3) drug abusers generally suffer from “dysfunctional personality resources” such as deficiency in memory, incapacity for psychological reflections, and lack of verbal and preverbal affect differentiation (alexithymia), (4) the conditions drug abusers must accept to receive clinical care, activate manipulative behaviour and latent defence mechanisms during interviews. Projective tests were also discussed as personality assessment. These methods were explored in relation to Freud's topographical model.

Mental disorders in patients with acute necrotic pancreatitis

The prognosis of patients with acute pancreatitis is still uncertain regardless of modern therapeutic procedures. It is even more emphasized if the acute pancreatitis is followed by psychic disorders. The aim of the study was to provide an overview of the incidence of certain psychosomatic disorders in patients with acute pancreatitis and evaluate priority therapeutic procedures. In this study, we analysed 16 patients with psychosomatic disorders followed by the episode of acute pancreatitis among 202 patients that were hospitalized in the period from 1993 until 2000. The diagnosis was based on anamnesis, clinical and laboratory findings and diagnostic procedures such as X-ray, US, CT and MRI. Among 16 patients with psychosomatic disorders followed by acute pancreatitis, 13 (81.25%) patients were operated on and 3 (18.75%) patients were medically treated. 6 patients experienced hallucinations, 5 memory deficiency, 16 disorientation and 14 confabulation. Psychosomatic disorders in patients with acute pancreatitis require complex medical treatment. Due to the already mentioned complications, the management of these conditions is very difficult and with uncertain results.

What do Dopamine Transporter and Catechol-O-Methyltransferase Tell us About Attention Deficit–Hyperactivity Disorder? Pharmacogenomic Implications

The purpose of the present paper was to review studies of two candidate genes for attention deficit-hyperactivity disorder (ADHD) and to separate aetiological from therapeutic effects. Genomic studies of ADHD were reviewed for candidate dopamine genes and studies selected to distinguish catechol-o-methyltransferase (COMT) and dopamine transporter (DAT-1) effects. Pharmacogenomic findings for the COMT gene were in agreement with the 1977 observations of Sprague and Sleator, who reported that at low psychostimulant doses, children with ADHD showed a remarkable improvement on a short-term memory test at all levels of task load, whereas at higher doses, there was a significant decrement in performance on the more difficult versions of the task, corresponding to an 'inverted 'U' shaped curve'. Recent studies show that individuals with the homozygous COMT (valine/valine) genotype demonstrated improvement following psychostimulant treatment, because their tonic dopamine (DA) levels were low, whereas the homozygous COMT (methionine/methionine) individuals, who already have high initial prefrontal cortex (PFC) dopamine levels performed more poorly after medication, in tasks with high working memory load. On the other hand aetiological findings for DAT-1 gene were heterogenous, but more often positive than for COMT. Contrasting findings for COMT and DAT-1 may best be considered in terms of prediction of medication response in ADHD in the case of COMT, but in aetiological terms in the case of DAT-1, which is abundant in the striatum and possibly plays a greater role in determining hyperactivity and impulsivity, than working memory deficiencies.

Using Reiki to Decrease Memory and Behavior Problems in Mild Cognitive Impairment and Mild Alzheimer's Disease

This empirical study explored the efficacy of using Reiki treatment to improve memory and behavior deficiencies in patients with mild cognitive impairment or mild Alzheimer's disease. Reiki is an ancient hands-on healing technique reputedly developed in Tibet 2500 years ago. This study was a quasi-experimental study comparing pre- and post-test scores of the Annotated Mini-Mental State Examination (AMMSE) and Revised Memory and Behavior Problems Checklist (RMBPC) after four weekly treatments of Reiki to a control group. The participants were treated at a facility provided by the Pleasant Point Health Center on the Passamaquoddy Indian Reservation. The sample included 24 participants scoring between 20 and 24 on the AMMSE. Demographic characteristics of the sample included an age range from 60 to 80, with 67% female, 46% American Indian, and the remainder white. Twelve participants were exposed to 4 weeks of weekly treatments of Reiki from two Reiki Master-level practitioners; 12 participants served as controls and received no treatment. The two groups were compared on pre- and post-treatment scores on the AMMSE and the Revised Memory and Behavior Problems Checklist (RMBPC). Results indicated statistically significant increases in mental functioning (as demonstrated by improved scores of the AMMSE) and memory and behavior problems (as measured by the RMBPC) after Reiki treatment. This research adds to a very sparse database from empirical studies on Reiki results. The results indicate that Reiki treatments show promise for improving certain behavior and memory problems in patients with mild cognitive impairment or mild Alzheimer's disease. Caregivers can administer Reiki at little or no cost, resulting in significant societal value by potentially reducing the needs for medication and hospitalization.

Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease

In recent years, the most common pharmacological treatment for Alzheimer's disease (AD) has been acetylcholinesterase (AChE) inhibition. However, this single-target approach has limited effectiveness and there is evidence that a multitarget approach might be more effective. Huperzine A (HupA), a novel alkaloid isolated from a Chinese herb, has neuroprotective effects that go beyond the inhibition of AChE. Recent data have demonstrated that HupA can ameliorate the learning and memory deficiency in animal models and AD patients. Its potentially beneficial actions include modification of beta-amyloid peptide processing, reduction of oxidative stress, neuronal protection against apoptosis, and regulation of the expression and secretion of nerve growth factor (NGF) and NGF signaling.

Cognitive impairment related changes in the elemental concentration in the brain of old rat

In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.

ICOS Deficiency Is Associated with a Severe Reduction of CXCR5+CD4 Germinal Center Th Cells

ICOS is expressed on activated T cells and particularly on CXCR5+ follicular Th cells in germinal centers (GC). Its deletion leads to a profound deficiency in memory B cell formation and switched Ab response in humans. Here, we show that in ICOS-deficient patients the generation of GCs is severely disturbed, and the numbers of circulating CXCR5+CD45RO+ memory CD4 T cells are significantly reduced, indicating an essential role of ICOS in the differentiation of CXCR5+CD4 T cells. The GC-specific CD57+CXCR5+ subpopulation is virtually absent. In ICOS-/- mice, the decrease of circulating CXCR5+CD4 T cells reflects the reduction of CXCR5+ follicular Th cells in lymph nodes and spleen. Therefore, in concurrence with the absence of CXCR5+ T cells in the blood of CD40L-deficient patients, these data support the hypothesis that circulating CD57+CXCR5+ T cells are GC derived and thus may serve as a surrogate marker for the presence of functional GCs in humans.

Aging: Compensation or maturation?

Neuroimaging studies of healthy aging often reveal differences in neural activation patterns between young and elderly groups for episodic memory tasks, even though there are no differences in behavioral performance. One explanation typically offered is that the elderly compensate for their memory deficiencies through the recruitment of additional prefrontal regions. The present study of healthy aging compared magnetoencephalographic (MEG) timecourses localized to specific cortical regions in two groups of subjects (20–29 years and ≥65 years) during a visual delayed-match-to-sample (DMS) task. MR morphometrics and neuropsychological test results were also examined with the hope of providing insight into the nature of the age-related differences. The behavioral results indicated no differences in performance between young and elderly groups. Although there was a main effect of age on the latency of the initial peak in primary/secondary visual cortex, these longer latencies were not correlated with the performance of elderly on the DMS task. The lateral occipital gyrus (LOG) revealed qualitatively different patterns of activity for the two age groups corroborated by neuropsychological test results. Morphometric results for the young versus elderly groups revealed less white (WM) and gray matter (GM) volumes in the frontal lobes of the elderly. When a group of middle-aged subjects (33–43 years) was included in the morphometric analyses, the middle-aged subjects revealed statistically greater WM volumes in frontal and parietal cortex suggesting immature WM tracts in the young. Perhaps our elderly utilized a different strategy compared to the young due to the different brain maturation levels of these groups.

Conversational apprentices: Helping children become competent informants about their own experiences

Alleged victims of child abuse are often the only sources of information about the crimes, and this places them in the role of experts when conversing about their experiences. Despite developmental deficiencies in memory, cognition, communication skills, and social style, researchers have shown that children's informativeness in such conversations is profoundly shaped by the interviewing practices of their adult interlocutors. We review techniques that degrade children's performance as well as those that help children perform to the best of their abilities, and discuss how these findings have important implications for the ways in which children learn to converse and interact with adults, and for their understanding of the roles played by conversations in information exchange. When adult interviewers conduct developmentally appropriate interviews with children, they help children become competent informants about their experiences.

Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice

Alterations in neuronal morphology occur in the brain during normal aging, but vary depending on neuronal cell types and brain regions. Such alterations have been related to memory and cognitive impairment. Changes in hippocampal spine densities are thought to represent a morphological correlate of altered brain functions associated with hippocampal-dependent learning and memory. We therefore have analyzed the impact of aging on different hippocampal-dependent learning tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We found a significant decrease in spine numbers of basal CA1 dendrites and decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons. Furthermore, aged mice exhibited significant deficits in hippocampus-dependent learning tasks, such as the probe trial of the Morris water maze and T maze learning. Given the fact that there is no neuronal loss in the hippocampus in aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434-2440), we suggest that the memory and cognitive decline in the context of aging may be accompanied by rather subtle anatomical changes, such as numbers and morphology of dendritic spines.

Preattentive deficits in developmental disorders of scholastic skills

Working memory deficiency has been implicated in developmental disorders of scholastic skills. The auditory P50 component of event-related potentials reflecting preattentive processing was investigated in 38 children with developmental disorders of scholastic skills and 19 sibling control children, as elicited during a working memory test. The P50 was evoked by two tones of low and high frequency (500 Hz and 3000 Hz). The group with developmental disorders of scholastic skills showed prolonged P50 latency induced by the low tone, located at the frontal area. The amplitude of P50 induced by the low tone exhibited significantly negative associations with both age and memory performance, whereas age and memory performance were associated positively. These findings indicate that preattentive processing deficits may be implicated not only in auditory cognition but also in developmental disorders of scholastic skills.

Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor α1 can be ameliorated by T3 treatment

The transcriptional properties of unliganded thyroid hormone receptors are thought to cause the misdevelopment during hypothyroidism of several functions essential for adult life. To specifically determine the role of unliganded thyroid hormone receptor alpha1 (TRalpha1) in neuronal tissues, we introduced a mutation into the mouse TRalpha1 gene that lowers affinity to thyroid hormone (TH) 10-fold. The resulting heterozygous mice exhibit several distinct neurological abnormalities: extreme anxiety, reduced recognition memory, and locomotor dysfunction. The anxiety and memory deficiencies were relieved by treatment with high levels of TH in adulthood, an effect that correlated with a normalization of GABAergic inhibitory interneurons in the hippocampal CA1 region. In contrast, a post-natal TH treatment was necessary and sufficient for ameliorating the adult locomotor dysfunction. Here, the hormone treatment normalized the otherwise delayed cerebellar development. The data thus identify two novel and distinct functions of an unliganded TRalpha1 during development and adulthood, respectively.

Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion

Diazoxide is a putative mitochondrial, ATP-sensitive potassium channel opener that has been implicated in neuroprotection in cerebral ischemia. Administered as pretreatment, diazoxide can attenuate ischemia-related neuronal injury, but little is known about the potential neuroprotective properties of the drug when it is given after the onset of an ischemic insult. In a previous study, we applied diazoxide after imposing chronic cerebral hypoperfusion by means of permanent, bilateral occlusion of the common carotid arteries (2VO) in rats. We observed that ischemia-induced learning impairment assessed in the Morris water maze, and microglial activation visualized by immunocytochemistry, were prevented by diazoxide as determined at 13 weeks after 2VO. However, dimethyl sulfoxide, the organic solvent of diazoxide also prevented memory deficits, without any effect on microglial activity. Therefore, we have repeated our experiments with the use of an inorganic solvent, aqueous NaOH solution in order to clarify the effect of diazoxide independent of dimethyl sulfoxide. The present results demonstrated that diazoxide alone did not improve learning performance, but it prevented microglial activation in the hippocampus 13 weeks after the onset of 2VO. These data provide evidence that post-treatment with diazoxide is not effective in impeding a long-term memory deficiency, but it can attenuate ischemia-induced microglial activation, independently of the solvent used.

Abnormal Long-Lasting Synaptic Plasticity and Cognition in Mice Lacking the Mental Retardation GenePak3

Mutations in the Pak3 gene lead to nonsyndromic mental retardation characterized by selective deficits in cognition. However, the underlying mechanisms are yet to be elucidated. We report here that the knock-out mice deficient in the expression of p21-activated kinase 3 (PAK3) exhibit significant abnormalities in synaptic plasticity, specifically hippocampal late-phase long-term potentiation, and deficiencies in learning and memory. A dramatic reduction in the active form of transcription factor cAMP-responsive element-binding protein in the knock-out mice implicates a novel signaling mechanism by which PAK3 and Rho signaling regulate synaptic function and cognition.