Impaired Recognition Research Articles

Cognitive Impairment in Primary Open Angle Glaucoma: A Case Control Study.

Cognitive impairment in multiple domains was observed in primary open angle glaucoma patients as compared to age and gender matched healthy controls. Evaluation of cognitive impairment in individuals with Primary Open Angle Glaucoma (POAG). In this case-control study, individuals with POAG (cases, n=70) were compared with age- and sex-matched healthy individuals (controls, n=70) using detailed ophthalmological evaluation, cognitive assessment and serum cortisol level. A multitude of tests were employed to comprehensively assess various domains of cognitive function: Addenbrooke Cognitive Examination (ACE-III; attention/orientation, memory, language, verbal fluency, and visuospatial skills), Post Graduate Institute Memory Scale (PGIMS; verbal and non verbal memory), Wisconsin Card Sorting Test (WCST; nonverbal executive functions), Go No-Go task (GNG; inhibitory control), and Trail Making Test (TMT; attention and working memory). Intraocular pressure and cup disc ratio were significantly higher (P <0.001) while retinal nerve fibre layer (RNFL) thickness and mean deviation were significantly lower in cases as compared to controls. Cases had significantly lower scores on ACE-III and PGIMS (P<0.001) and longer test completion time in TMT-A (P=0.001). The performance of cases was also significantly worse on most parameters of the WCST and GNG tasks. Serum cortisol level was significantly higher in cases (11.75±7.41mcg/dl) compared to controls (7.93±2.39 mcg/dl; P=0.02). A significant correlation was observed between serum cortisol level and WCST correct response (P=0.04), WCST error response (P=0.002) and total time taken in TMT-A (P=0.03).Visual field mean deviation also exhibited a significant correlation with serum cortisol level (P<0.001) and total time taken on WCST (P=0.03) and TMT-A (P=0.03). Individuals with POAG exhibited higher cognitive impairment and raised serum cortisol levels than age-matched healthy controls. Early recognition and management of cognitive impairment are pivotal for enhancing the quality of life and implementing comprehensive glaucoma care.

Tau oligomers impair memory and synaptic plasticity through the cellular prion protein

Deposition of abnormally phosphorylated tau aggregates is a central event leading to neuronal dysfunction and death in Alzheimer’s disease (AD) and other tauopathies. Among tau aggregates, oligomers (TauOs) are considered the most toxic. AD brains show significant increase in TauOs compared to healthy controls, their concentration correlating with the severity of cognitive deficits and disease progression. In vitro and in vivo neuronal TauO exposure leads to synaptic and cognitive dysfunction, but their mechanisms of action are unclear. Evidence suggests that the cellular prion protein (PrPC) may act as a mediator of TauO neurotoxicity, as previously proposed for β-amyloid and α-synuclein oligomers. To investigate whether PrPC mediates TauO detrimental activities, we compared their effects on memory and synaptic plasticity in wild type (WT) and PrPC knockout (Prnp0/0) mice. Intracerebroventricular injection of TauOs significantly impaired recognition memory in WT but not in Prnp0/0 mice. Similarly, TauOs inhibited long-term potentiation in acute hippocampal slices from WT but not Prnp0/0 mice. Surface plasmon resonance indicated a high-affinity binding between TauOs and PrPC with a KD of 20–50 nM. Immunofluorescence analysis of naïve and PrPC-overexpressing HEK293 cells exposed to TauOs showed a PrPC dose-dependent association of TauOs with cells over time, and their co-localization with PrPC on the plasma membrane and in intracellular compartments, suggesting PrPC-may play a role in TauO internalization. These findings support the concept that PrPC mediates the detrimental activities of TauOs through a direct interaction, suggesting that targeting this interaction might be a promising therapeutic strategy for AD and other tauopathies.

Glutamate transporter activator LDN-212320 prevents chronic pain-induced cognitive impairment and anxiety-like behaviors in a mouse model.

The astroglial glutamate transporter in the hippocampus and anterior cingulate cortex (ACC) is critically involved in chronic pain-induced cognitive and psychiatric abnormalities. We have previously reported that LDN-212320, a glutamate transporter-1 (GLT-1) activator, attenuates complete Freund's adjuvant (CFA)-induced acute and chronic nociceptive pain. However, the cellular and molecular mechanisms underlying GLT-1 modulation in the hippocampus and ACC during chronic pain-induced cognitive deficit-like and anxiety-like behaviors remain unknown. Here, we have investigated the effects of LDN-212320 on CFA-induced chronic pain associated with cognitive deficit-like and anxiety-like behaviors in mice. We have evaluated the effects of LDN-212320 on CFA-induced impaired spatial, working, and recognition memory using Y-maze and object-place recognition tests. In addition, we have determined the effects of LDN-21230 on chronic pain-induced anxiety-like behaviors using elevated plus maze and marble burying test. We have also examined the effects of LDN-212320 on cAMP response element-binding protein (pCREB), brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) expression in the hippocampus and ACC during CFA-induced cognitive deficit-like and anxiety-like behaviors using the Western blot analysis and immunofluorescence assay. Pretreatment with LDN-212320 (20 mg/kg) significantly attenuated CFA-induced impaired spatial, working, and recognition memory. Furthermore, LDN-212320 (20 mg/kg) significantly reduced CFA-induced anxiety-like behaviors. Additionally, LDN-212320 (20 mg/kg) significantly reversed CFA-induced decreased pCREB, BDNF, PKA and CaMKII expression in the hippocampus and ACC. Overall, these results suggest that the LDN-212320 prevents CFA-induced cognitive deficit-like and anxiety-like behaviors by activating CaMKII/CREB/BDNF signaling pathway in the hippocampus and ACC. Therefore, LDN-212320 could be a potential treatment for chronic pain associated with cognitive impairment and anxiety-like behaviors.

The Impact of Astroglia Kir4.1 Channel Dysfunction on Neuronal Activity and Autism-Related Behavioral Abnormalities.

Autism spectrum disorder (ASD) is marked by neurobehavioral developmental deficits, potentially linked to disrupted neuron-glia interactions. The astroglia Kir4.1 channel plays a vital role in regulating potassium levels during neuronal activation, and mutations in this channel have been associated with ASD. This study investigates astroglia Kir4.1 as a regulator of neuronal excitability and behavioral abnormalities in rats with autistic-like traits induced by prenatal exposure to valproic acid (VPA). Whole-cell patch-clamp recordings were obtained from pyramidal neurons in the hippocampal CA1 region, showing that inhibition of Kir4.1 channels led to electrophysiological changes indicative of neuronal hyperexcitability, similar to that seen in VPA-exposed neurons. Specifically, there was increased input resistance and voltage threshold, alongside decreased time constant and rheobase. Behavioral assessments after 7 days of intrahippocampal PA6 (5 μg/mL/day) administration revealed significant social withdrawal, heightened anxiety, reduced exploration, and impaired recognition memory, underscoring the behavioral deficits linked to autism. While Kir4.1 inhibition affected excitability, it did not alter the output of CA1 pyramidal neurons in autistic-like rats. These findings emphasize the critical role of astroglia Kir4.1 channels in modulating neuronal excitability and associated behavioral impairments within the VPA-induced autism model, suggesting a promising target for future therapeutic interventions.

Functional Proteins/Peptides Targeting to Clear Amyloid-β for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is a significant neurodegenerative disorder primarily affecting individuals over the age of 65. It is characterized by impairments in memory, thinking, analytical judgment, visuospatial recognition, and mood. In recent years, the development of protein and peptide drugs targeting amyloid-beta (Aβ) has gained momentum, with several therapies entering clinical trials and even receiving marketing approval. Novel functional protein and peptide drugs, as the first-generation immunotherapeutic agents for neurodegenerative diseases, have pioneered cellular immunotherapy for AD. However, the currently available drugs are associated with toxicity issues, which can lead to serious complications such as cerebral hemorrhage or edema. Consequently, this study examines the potential for a new generation of Aβ-targeting drugs to mitigate the side effects of existing treatments and offers innovative perspectives for the advancement of therapies for AD.

Restraint stress effects on glutamate signaling protein levels in the rats' frontal cortex: Does β1 adrenoceptor activity matter?

Stress-evoked dysfunctions of the frontal cortex (FC) are correlated with changes in the functioning of the glutamatergic system, and evidence demonstrates that noradrenergic transmission is an important regulator of this process. In the current study, we adopted a restraint stress (RS) model in male Wistar rats to investigate whether the blockade of β1 adrenergic receptors (β1AR) with betaxolol (BET) in stressed animals influences the body's stress response and the expression of selected signaling proteins in the medial prefrontal cortex (mPFC). The study was divided into two parts. In the first part, rats were exposed to RS for 3, 7, or 14days, and the expression of glutamate signaling proteins (p(S845)/t GluA1, p(Y1472)/t GluN2B, VGLUT1, and VGLUT2) in the FC was analyzed to determine the optimal RS duration for studying the mechanisms of hypofrontality. In the second part, rats were exposed to RS for 14days, and BET (5mg/kg, p. o.) was administered during the last 8days immediately after RS. The body's stress reaction was assessed by analyzing body weight and blood levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Behavioral responses were evaluated using the novel object recognition (NOR) and elevated plus maze (EPM) tests. The impact of RS and BET on the expression of p(Y530)/t Fyn and p (S133)/t CREB in the mPFC was measured via Western blotting. The first part of the study demonstrated a decreased level of glutamate receptors in rats exposed to 14days of RS, following an initial increase observed after 7days of RS. Results from the second part revealed that chronic RS reduced body weight, impaired recognition memory in the NOR test, augmented blood levels of ACTH, and increased the expression of p(Y530) Fyn in the mPFC. However, β1AR blockade did not alter the effects of RS on weight gain, cognitive function, or the expression of p(Y530) Fyn. β1AR blockade normalized only the blood concentration of ACTH. These results suggest that decreased Fyn kinase activity, indicated by phosphorylation at Y530, underlies the stress-evoked downregulation of GluN2B in the FC in a manner independent of β1AR activity.

Org24598, a Selective Glycine Transporter 1 (GlyT1) Inhibitor, Reverses Object Recognition and Spatial Memory Impairments Following Binge-like Ethanol Exposure in Rats.

The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol, and it is implicated in learning and memory formation, and other cognitive functions. Glycine acts as a co-agonist for this receptor. We examined whether Org24598, a selective inhibitor of glycine transporter1 (GlyT1), affects ethanol withdrawal-induced deficits in recognition memory (Novel Object Recognition (NOR) task) and spatial memory (Barnes Maze (BM) task) in rats, and whether the NMDA receptor glycine site participates in this phenomenon. Male Wistar rats were habituated to NOR or BM tasks, and then received binge-like intragastric ethanol administration (5 days, 5 g/kg). After ethanol withdrawal, Org24598 (0.1, 0.3, and 0.6 mg/kg) was administered 30 min before NOR (day 10 of withdrawal) or the reversal learning phase of BM (day 11-13 of withdrawal) task. The expression of GluN1 and GluN2B subunits of NMDA receptors were measured in the perirhinal cortex (PRC) and hippocampus (HIP) after termination of NOR. In the BM task, a glycine antagonist, L-701,324 (5 mg/kg), was administered 30 min before Org24598 to confirm the involvement of the NMDA receptor glycine site in the effects of Org24598. Our study showed that binge-like ethanol administration induced recognition and spatial memory impairments after withdrawal in rats. Additionally, an up-regulation of GluN1 and GluN2B subunits of the NMDA receptor was observed in the HIP and PRC on day 11 of abstinence. Org24598 ameliorated memory loss and normalized the expression of these subunits. L-701,324 reversed the effect of Org24598. Thus, NMDA receptor glycine sites are important in ethanol withdrawal-induced memory impairments.

Differential effects of disease duration and dopaminergic replacement therapy on vocal emotion recognition in asymmetric Parkinson's disease.

Recently, studies have suggested a role of motor symptom asymmetry on impaired emotional recognition abilities in Parkinson's disease with a greater vulnerability in patients with a predominance of left-sided symptoms. However, none of them explored the interaction between motor symptom asymmetry and dopamine replacement therapy in different stages of the disease. We explored the recognition of vocal emotion (i.e., emotional prosody) in 15 newly diagnosed Parkinson's disease patients in the early stages of the disease, 15 patients in the advanced stages of the disease and 15 healthy controls. The early patients were studied in two conditions: ON and OFF dopaminergic replacement therapy and both Parkinson's disease groups (early and advanced) were divided into two subgroups according to the asymmetry of motor symptoms. The analyses revealed two patterns of results. First, as predicted, we observed a reduction in performance for the recognition of vocal emotions in patients with a predominance of left-sided symptoms as compared to both healthy controls and predominantly right-sided symptom patients. Secondly, in the early stages of the disease, we observed a deleterious effect of dopatherapy on the recognition of vocal emotions for the patients with left-predominant symptoms, and the reversal pattern for the patients with right-predominant symptoms. Our results bring to our knowledge the differential effects of disease duration, dopaminergic replacement therapy and motor symptom asymmetry on vocal emotion recognition in Parkinson's disease.

Homoplantaginin Antagonizes N-Methyl-d-aspartate Receptor and Extracellular Signal-Regulated Kinase Signaling in Aβ Oligomers-Induced Neuropathology/Toxicity.

Extracts from plants/herbals are great resources of drugs and nutrients. Baicalein, a component present in Scutellaria baicalensis, was previously found to alleviate the abnormal depolarization brought about by Aβ oligomers. We extended this promising outcome by screening baicalein derivatives, and a natural compound named homoplantaginin was pinpointed. In this study, we aimed to investigate the effects of homoplantaginin on animal behavior and explore its neuronal functioning/mechanism. In behavior tests, impairments of novel object recognition and of spatial learning/memory were reversed by homoplantaginin in a J20 Alzheimer's disease (AD) mouse model. Utilizing primary glutamatergic neurons, homoplantaginin was found to prevent the Aβ oligomer-induced increase in ERK phosphorylation. Furthermore, homoplantaginin inhibits both AMPA-insult and NMDA-insult depolarization; this was assessed using DiBAC4(3), a membrane potential sensitive dye. Finally, homoplantaginin blocks both Aβ oligomer-induced and NMDA-induced calcium influx, which was assessed by intracellular calcium measurement using Fura2/AM. Interestingly, homoplantaginin immediately blunts the steady state calcium influx caused by NMDA. Taken together, homoplantaginin is capable of inhibiting Aβ oligomer-induced pathophysiology, in particular at the receptor level. This pure compound has great potential to be developed as a clinical therapeutic drug.

Anxio-depressive phenotype and impaired memory in mice with a conditional knockout of brain-derived neurotrophic factor in endothelial cells.

The present study investigated the role of endothelial brain-derived neurotrophic factor (BDNF) in cognition. Male adult mice with a selective knockout of BDNF in endothelial cells (BDNFECKO) and their wild-type (WT) littermates were subjected to tests for detection of anxiety- and depression-like behaviors and impaired recognition memory. Neuronal activity and synaptogenesis were assessed from hippocampal levels of c-fos and synaptophysin, respectively, and cerebral capillary density from forebrain levels of CD31. BDNF/TrkB (tropomyosin-related kinase type B) receptor signaling was investigated through hippocampal levels of BDNF and activated TrkB receptors coupled with their immunolabeling by neurons and endothelial cells from both cerebrovascular fractions enriched in capillaries and hippocampal arterioles. Endothelial nitric oxide (NO) production was assessed from the expression of endothelial NO synthase phosphorylated at serine 1177. BDNFECKO mice exhibited anxio-depressive phenotype, impaired memory, and reduced synaptogenesis. Neither neuronal activity, neuronal BDNF/TrkB signaling, nor capillary density differed between BDNFECKO and WT mice. However, endothelial-activated TrkB receptors as well as endothelial NO production and hippocampal BDNF levels were lower in BDNFECKO than those in WT mice. We conclude that endothelial BDNF is involved in cognition through mechanisms independent of neuronal BDNF/TrkB signaling and that endothelial NO might be a driver of the procognitive effect of endothelial BDNF.NEW & NOTEWORTHY The study provides the proof of concept that endothelial brain-derived neurotrophic factor (BDNF) plays a crucial role in postnatal synaptogenesis and development of behavior/memory. It also shows that neuronal tropomyosin-related kinase type B (TrkB) receptors are not a target of endothelium-derived BDNF.

Developmental Trajectory of Autistic-Like Behaviors in a Prenatal Valproic Acid Rat Model of Autism.

Autism spectrum disorders (ASDs) are characterized by deficits in social functioning, stereotyped patterns of behaviors, narrowed interests, and elevated anxiety. Certain ASD symptoms can persist, whereas others may improve throughout the lifespan, but the specific patterns of changes have not been clearly delineated. Using a valproic acid (VPA) rat model of ASD, the present study took a developmental approach and examined how autistic-like behaviors, including anxiety-like behavior, object obsession, and social functioning deficits, manifested differently in three critical periods representing preadolescent (postnatal day [PND] 25), adolescent (PND 45), and adulthood life stage (PND 75) in a sex-dependent manner. Starting on PNDs 25, 45, and 75, VPA- or saline-exposed male and female offspring were tested in an elevated plus maze (EPM) and a newly validated composite social and object interaction and a triple recognition test (object, spatial, and social recognition). Across the three age groups, VPA-exposed offspring did not exhibit enhanced anxiety-like behavior in the EPM nor enhanced object interaction ("object obsession") in the triple recognition test. However, both male and female preadolescent (PND 25) VPA-exposed offspring showed a significantly increased latency to initiate social contact than the saline-exposed controls, although their latencies to contact novel objects were comparable to those of the controls. Male preadolescent and adolescent VPA-exposed offspring, to a lesser extent the female preadolescent offspring, exhibited significantly lower levels of social interaction. These social functioning deficits were absent in adult VPA offspring. Additionally, prenatal VPA exposure did not cause an impairment of object recognition, spatial recognition, or social recognition of a familiar conspecific. Unexpectedly, it enhanced social recognition of a novel conspecific, but only in adolescent female offspring. These findings suggest that this rat model based on prenatal VPA exposure is valid in capturing early social motivational and functioning deficits but is limited in its capacity to model increased object obsession and enhanced anxiety as seen in ASD, as well as the developmental trajectory of non-social ASD symptoms. Recognizing these limitations is important as it informs us how to properly use this model to investigate the neurobiology of ASD and incentivizes us to develop better rodent models.

Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague-dawley rat.

The prevalence of hypertension increases with age and is the leading modifiable risk factor for cognitive impairment and dementia. At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague-Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus enhances sympathetic tone and contributes to age-dependent hypertension, (2) age-dependent hypertension is associated with cognitive impairment, and (3) lowering blood pressure in aged rats with established hypertension improves cognitive function. We found male, but not female, rats develop age-dependent hypertension with enhanced sympathetic tone, BBB disruption, and neuroinflammation in the PVN. Aged hypertensive male rats also showed impairments in recognition and spatial memory. Utilizing pharmacological interventions, blood pressure was lowered in male rats with established hypertension using either losartan (LOS) or hydrochlorothiazide. However, only losartan improved recognition memory. Further, LOS reduced BBB disruption, microglial activation, astrocyte reactivity, and proinflammatory cytokine expression in the PVN which we speculate contributes to a decrease in blood pressure. These data show SD rats develop age-dependent hypertension and cognitive impairment in a sex-dependent manner. However, not all antihypertensive agents improve cognitive function equally as only losartan, an angiotensin II type 1 receptor antagonist (AT1R) improved recognition memory. Thus, AT1R antagonists represent a potential therapeutic approach for treating cognitive decline in the aging population.

Slight and hidden hearing loss in young rats is associated with impaired recognition memory and reduced myelination in the corpus callosum.

Slight and hidden hearing loss in children have been linked to cognitive and social difficulties, and yet the neurobiological mechanisms behind these issues remain poorly understood. Most animal models focus on severe hearing loss, leaving the effects of hidden or slight hearing loss largely unexplored. To uncover the neural mechanisms connecting slight/hidden hearing loss to cognitive and social challenges, we induced hearing loss in young (4-week-old) Wistar rats through noise exposure. We then examined cognitive function (object recognition test) and social behavior (juvenile play behavior and social interaction). Changes in brain anatomy were assessed using cortical thickness and hippocampal size measurements, while (immuno)histochemical staining investigated neuronal circuitry maturation (myelin basic protein, parvalbumin, and perineuronal nets) and neurogenesis (doublecortin). Noise-exposed rats displayed slight high-frequency hearing loss (around 20 dB) and hidden hearing loss at other tested frequencies. This slight/hidden hearing loss was associated with impaired object recognition but did not alter social behavior. Slight/hidden hearing loss was associated with reduced myelin basic protein expression in the corpus callosum but no other alterations in cortical thickness, hippocampal size, or other markers of maturation and neurogenesis were found. These findings show that even slight/hidden hearing loss can lead to subtle brain alterations tied to cognitive deficits. This study emphasizes the need for further research to fully understand the brain changes associated with slight/hidden hearing loss and to pinpoint the mechanisms connecting these changes to behavioral deficits. This information is crucial to develop interventions to prevent the cognitive and social consequences of hearing loss. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Chronic cannabidiol administration modulates depressive and cognitive alterations induced by social isolation in male mice.

Cannabidiol (CBD), a non-psychotropic compound derived from Cannabis sativa, is known for its potential therapeutic effects on central nervous system (CNS) disorders. This study investigates the effects of chronic CBD administration on depressive and cognitive alterations induced by social isolation in male C57BL/6 mice. The experimental design involved adult mice subjected to either group housing or 12 weeks of social isolation. Behavioral assessments, including the sucrose preference test, open field test, light/dark box, novel object recognition, and tail suspension test, were performed to evaluate the impact of CBD on emotional and cognitive alterations. Additionally, hippocampal gene expression for cannabinoid type 1 receptors (CB1R), serotonin type 1A receptors (5HT1AR), and brain-derived neurotrophic factor (BDNF) were analyzed. Results indicate that CBD mitigated anhedonia in isolated mice and reduced immobility episodes in the TST. However, CBD did not exert significant anxiolytic effects and unexpectedly induced anxiety-like behavior in group-housed mice. The study also revealed that social isolation impaired recognition memory and reduced BDNF expression, while CBD treatment protected memory in isolated mice. These findings suggest that CBD has potential antidepressant and neuroprotective effects in social isolation-induced depressive models, although its anxiogenic effects in non-stressed mice warrant further investigation.

Recognition of mild cognitive impairment in older adults using a polynomial regression model based on prefrontal cortex hemoglobin oxygenation

AimThis study employed a three-minute game-based intelligence test (GBIT) to create a hemoglobin polynomial regression model for early identification of mild cognitive impairment (MCI) in older adults. Methods210 older adult participants were recruited from community centers in the central region of Taichung City. Working memory (WM) performance in older adults was assessed during GBIT, while hemoglobin responses were measured by near-infrared spectroscopy (NIRS). Variables included oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb). Data sequences underwent a fitting procedure using a transformed cubic polynomial function. The transformed coefficients were used as predictors of a logistic regression model to recognize MCI in older adults. ResultsThis study confirmed the relationship between age and cognitive performance. The findings demonstrate that the NIRS cubic polynomial function trends during the GBIT test showed significant changes in older adults, increasing with age. Logistic regression analysis identified age and the orientation (coefficient a) of HHb as the main factors for recognizing MCI. The model achieved an overall precision of 83.33 % (sensitivity = 75.00 %; specificity = 84.68 %) with the formula: ln (Odds [MCI]) = −1.64 + 0.57 × HHb_a + 1.40 × age. ConclusionsNIRS hemoglobin response characteristics during GBIT may serve as an efficient indicator of MCI in older adults. These findings may advance the field of cognitive health evaluation, resulting in earlier detection of cognitive deterioration in older adults.

Research progress on hidden hearing loss

Hidden hearing loss (HHL) is a type of hearing impairment characterized by normal pure tone threshold audiometry (PTA) but impaired speech recognition and coding ability in noisy environments. At present, synaptic and nerve damage is the most likely pathological mechanism of HHL. Noise exposure, aging and ototoxic drugs may affect the occurrence of HHL, but its clinical manifestations and routine examinations have no obvious abnormalities, which may easily lead to missed diagnosis of HHL. This article reviews the current research status of HHL, including its possible pathogenesis, influencing factors, clinical diagnosis and treatment methods, and puts forward its future research direction, in order to provide basis for the early prevention, diagnosis and treatment of HHL.

Scopolamine animal model of memory impairment

In this study, we reassessed the suitability of a commonly used pharmacological animal model of Alzheimer’s disease (AD) – scopolamine-induced memory impairment. The goal of the study was to explore if this animal model induces other behavioral changes associated with AD. One of the key behavioral features of AD, manifesting already during the early stages of the illness, is apathy-like behavior. We also evaluated how behavioral alterations induced by scopolamine compare to those seen in healthy aging animals. To achieve these goals, locomotor activity and short-term memory of young male Wistar rats were tested in the open field, novel object recognition (NOR) and T-maze spontaneous alternation tests before, during and after 21 daily administrations of scopolamine. Three-, ten- and nineteen-month-old male and female rats were used to measure age-related changes in these behaviors. Our data showed that although both scopolamine treatment and aging reduced the number of approaches to the objects and their exploration time during the NOR test, correlation with impaired object recognition memory was only observed in the scopolamine treated animals. Furthermore, treatment with scopolamine significantly increased the locomotor activity, which could be observed even one week after treatment discontinuation. Contrary, locomotor activity in older rats was significantly lower than that of younger rats. These findings demonstrate that the animal model of scopolamine-induced memory impairment fails to incorporate apathy-like symptoms characteristic to the AD and age-related reduction in physical activity of older rats.

Influence of the Nucleo-Shuttling of the ATM Protein on the Response of Skin Fibroblasts from Marfan Syndrome to Ionizing Radiation.

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder affecting multiple systems, such as skeletal, cardiovascular, and ocular systems. MFS is predominantly caused by mutations in the FBN1 gene, which encodes the fibrillin-1 protein, crucial for connective-tissue integrity. FBN1 mutations lead to defective fibrillin, resulting in structurally compromised connective tissues. Additionally, these mutations cause aberrant TGF-β expression, contributing to vascular issues and increased susceptibility to radiation-induced fibrosis. Studies about the potential radiosensitivity of MFS are rare and generally limited to case reports. Here, we aimed to investigate the radiation-induced ATM nucleo-shuttling (RIANS) model to explore the molecular and cellular radiation response in fibroblasts from MFS patients. The results showed that the MFS fibroblast cell lines tested are associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired recognition of DNA double-strand breaks (DSBs) caused by a diminished RIANS. The diminished RIANS is supported by the sequestration of ATM protein in the cytoplasm not only by mutated FBN1 protein but also by overexpressed TGF-β. This report is the first molecular and cellular characterization of the radiation response of MFS fibroblasts and highlights the importance of the FBN1-TGF-β complex after irradiation.

The prefrontal cortex, but not the medial temporal lobe, is associated with episodic memory in middle-aged persons with HIV.

Identifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined. We examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years). At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall. Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Early Impairment of Face Perception in Post-Stroke Depression: An ERP Study.

Objective: Face recognition is an important cognitive function of the human brain. Post stroke depression (PSD) is a common mental complication after stroke, which has a serious impact on individual physical function recovery and quality of life. This study aims to explore the face perception characteristics of PSD through electrophysiological indicators N170 and VPP, and provide an objective basis for the early evaluation of facial cognitive dysfunction in PSD. Methods: 58 patients in the cerebral small vessel disease (CSVD) with depressive symptoms (PSD) and 188 patients in the pure CSVD (NPSD). At the same time, 30 healthy subjects were selected as the healthy controls (HC). The differences of N170 and VPP components between the three groups were compared under the stimulation of inverted faces and upright faces. Results: PSD patients exhibited significantly longer peak latency and lower amplitude of N170 and VPP under both inverted and upright face stimulation compared to HC and NPSD. These results suggest that PSD patients have defects in early face recognition, there are abnormalities in the early perception and structural encoding of face information, and both the "overall mechanism" and "feature mechanism" of face recognition are damaged. Conclusions: These findings provide neuroelectrophysiological evidence for impaired emotionless face recognition in PSD patients.