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1.
Alzheimers Res Ther ; 16(1): 97, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702802

ABSTRACT

BACKGROUND: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls. METHODS: Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy. RESULTS: We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients. CONCLUSIONS: The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.


Subject(s)
Alzheimer Disease , Basal Nucleus of Meynert , Frontotemporal Dementia , Locus Coeruleus , Magnetic Resonance Imaging , Humans , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/pathology , Male , Locus Coeruleus/diagnostic imaging , Locus Coeruleus/pathology , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Female , Aged , Magnetic Resonance Imaging/methods , Basal Nucleus of Meynert/diagnostic imaging , Basal Nucleus of Meynert/pathology , Middle Aged , Neuropsychological Tests , Amnesia/diagnostic imaging , Positron-Emission Tomography/methods
2.
Brain Behav ; 14(5): e3507, 2024 May.
Article in English | MEDLINE | ID: mdl-38688895

ABSTRACT

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues. METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 µL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions. CONCLUSION: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.


Subject(s)
Acetylcholinesterase , Amnesia , Brain-Derived Neurotrophic Factor , Oils, Volatile , Rosa , Scopolamine , Animals , Rats , Amnesia/chemically induced , Amnesia/drug therapy , Amnesia/metabolism , Oils, Volatile/pharmacology , Oils, Volatile/administration & dosage , Male , Rosa/chemistry , Brain-Derived Neurotrophic Factor/metabolism , Acetylcholinesterase/metabolism , Receptor, Muscarinic M1/metabolism , Rats, Wistar , Nootropic Agents/pharmacology , Disease Models, Animal , Brain/drug effects , Brain/metabolism , Cognition/drug effects , Maze Learning/drug effects
3.
J Psychiatr Res ; 174: 220-229, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38653030

ABSTRACT

INTRODUCTION: Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between dissociative identity states. Studies have found conflicting results regarding memory transfer between dissociative identity states. Here, we investigated inter-identity amnesia in individuals with DID using self-relevant, subject specific stimuli, and behavioural and neural measures. METHODS: Data of 46 matched participants were included; 14 individuals with DID in a trauma-avoidant state, 16 trauma-avoiding DID simulators, and 16 healthy controls. Reaction times and neural activation patterns related to three types of subject specific words were acquired and statistically analysed, namely non-self-relevant trauma-related words (NSt), self-relevant trauma-related words from a trauma-avoidant identity state (St), and trauma-related words from a trauma-related identity state (XSt). RESULTS: We found no differences in reaction times between XSt and St words and faster reaction times for XSt over NSt. Reaction times of the diagnosed DID group were the longest. Increased brain activation to XSt words was found in the frontal and parietal regions, while decreased brain activity was found in the anterior cingulate cortex in the diagnosed DID group. DISCUSSION: The current study reproduces and amalgamates previous behavioural reports as well as brain activation patterns. Our finding of increased cognitive control over self-relevant trauma-related knowledge processing has important clinical implications and calls for the redefinition of "inter-identity amnesia" to "inter-identity avoidance".


Subject(s)
Amnesia , Dissociative Identity Disorder , Magnetic Resonance Imaging , Humans , Male , Female , Adult , Amnesia/physiopathology , Dissociative Identity Disorder/physiopathology , Young Adult , Reaction Time/physiology
4.
Neurochem Int ; 176: 105740, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636905

ABSTRACT

The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise.


Subject(s)
Amnesia , Anisomycin , Brain-Derived Neurotrophic Factor , Hippocampus , Physical Conditioning, Animal , Rats, Wistar , Animals , Male , Physical Conditioning, Animal/physiology , Rats , Hippocampus/metabolism , Hippocampus/drug effects , Anisomycin/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/biosynthesis , Amnesia/metabolism , Amnesia/prevention & control , Protein Synthesis Inhibitors/pharmacology , Sirolimus/pharmacology , Protein Biosynthesis/drug effects , Protein Biosynthesis/physiology , Memory Consolidation/drug effects , Memory Consolidation/physiology , Recognition, Psychology/drug effects , Recognition, Psychology/physiology
6.
Drug Des Devel Ther ; 18: 967-978, 2024.
Article in English | MEDLINE | ID: mdl-38562518

ABSTRACT

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.


Subject(s)
Amnesia, Anterograde , Dexmedetomidine , Respiratory Insufficiency , Humans , Amnesia/chemically induced , Amnesia, Anterograde/chemically induced , Benzodiazepines , Bronchoscopy/adverse effects , Dexmedetomidine/adverse effects , Hypnotics and Sedatives/adverse effects , Intubation, Intratracheal/adverse effects , Respiratory Insufficiency/chemically induced , Sufentanil , Wakefulness , Double-Blind Method
7.
Molecules ; 29(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38611808

ABSTRACT

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.


Subject(s)
Arsenic , Humic Substances , Animals , Mice , Amnesia , Antioxidants/pharmacology , Coal
8.
Int J Mol Sci ; 25(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38612521

ABSTRACT

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.


Subject(s)
Dihydroergotamine , Scopolamine , Animals , Rats , Histamine , Amnesia/chemically induced , Amnesia/drug therapy , Brain , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Histamine H2 Antagonists
9.
Pap. psicol ; 45(1): 34-38, Ene-Abr, 2024. graf
Article in English | IBECS | ID: ibc-229714

ABSTRACT

Se discute la validez de la memoria disociativa en contextos forenses y las causas de las llamadas “guerras de la memoria”. Conceptos erróneos entre la psicología clínica y la psicología forense, una definición deficiente de la amnesia y las dificultades inherentes en el estudio de recuerdos traumáticos contribuyen a la persistencia de esta controversia. Particularmente en el campo de la psicología forense, el debate podría atribuirse a la falta de consenso sobre la evidencia científica. Los psicólogos necesitan establecer una base empírica para comprender mejor los mecanismos de la memoria involucrados en recordar y olvidar recuerdos traumáticos. Se esboza el Modelo de Accesibilidad Continua de la Memoria para explicar la recuperación de los diferentes grados de accesibilidad a los recuerdos autobiográficos basados en diferentes factores.(AU)


The validity of dissociative memory in forensic contexts and the causes of the so-called “memory wars” arediscussed. Misconceptions between clinical and forensic psychology, a deficient definition of amnesia, and the difficulties inherent in studying traumatic memories contribute to the persistence of this controversy. Particularly in the field of forensic psychology, the debate could be attributed to the lack of consensus on scientific evidence. Psychologists need to establish an empirical foundation to understand better the mechanisms of memory involved in remembering and forgetting traumatic memories. The Continuous Accessibility Model of Memory is outlined to explain the retrieval of the different degrees of accessibility to autobiographical memories based on different factors.(AU)


Subject(s)
Humans , Male , Female , Amnesia , Mental Health , Forensic Psychology , Mental Recall , Psychology , Crime Victims
10.
Science ; 383(6688): 1172-1175, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38484046

ABSTRACT

The mystery of "infantile amnesia" suggests memory works differently in the developing brain.


Subject(s)
Amnesia , Brain , Child Development , Memory, Long-Term , Humans , Amnesia/physiopathology , Brain/growth & development , Infant , Animals , Mice , Child, Preschool , Rats
11.
Ugeskr Laeger ; 186(9)2024 02 26.
Article in Danish | MEDLINE | ID: mdl-38445321

ABSTRACT

This case report describes a 29-year-old man, who was admitted to a psychiatric hospital due to a severe depressive episode without psychotic symptoms. After two weeks he developed acute retrograde autobiographical amnesia. No organic cause was identified, and the patient was therefore diagnosed with dissociative amnesia. The depressive symptoms ceased as the amnesia developed. After five months of follow-up in the outpatient clinic, his amnesia for the time preceding its outbreak remained unchanged. He patient managed to resume a functional daily life.


Subject(s)
Amnesia , Depressive Disorder , Male , Humans , Adult , Ambulatory Care Facilities , Disease Outbreaks , Hospitalization
12.
Ann Clin Transl Neurol ; 11(5): 1236-1249, 2024 May.
Article in English | MEDLINE | ID: mdl-38553802

ABSTRACT

OBJECTIVES: Mild cognitive impairment presenting with an amnestic syndrome (aMCI) and amyloid positivity is considered due to AD. Many subjects, however, can show an overall very slow progression relevant for differential diagnosis, prognosis, and treatment. This study assessed PET biomarkers, including brain glucose metabolism, tau, and amyloid load, in a series of comparable aMCI at baseline, clinically evaluated at follow-up. METHODS: We included 72 aMCI subjects from Geneva Memory Center (N = 31) and ADNI cohorts (N = 41), selected based on available FDG-PET, tau-PET, amyloid-PET, and clinical follow-up (2.3 years ± 1.2). A data-driven algorithm classified brain metabolic patterns into subtypes that were then compared for clinical and PET biomarker measures and cognitive decline. Voxel-wise comparisons were performed both with FDG-PET and tau-PET data. RESULTS: The algorithm classified three metabolic subtypes, namely "Hippocampal-sparing with cortical hypometabolism" (Type1; N = 27), "Hippocampal and cortical hypometabolism" (Type 2; N = 23), and "Medial temporal hypometabolism" (Type 3; N = 22). Amyloid positivity and tau accumulation in the medial temporal and neocortical regions characterized Type 1 and Type 2, whereas Type 3 showed no significant tau pathology, variable amyloid positivity, and stability at follow-up. All tau-positive patients, independently of the FDG-based subtype, showed faster cognitive decline. INTERPRETATION: aMCI subjects can differ in metabolic patterns, tau and amyloid pathology, and clinical progression. Here, we complemented with PET tau biomarker the specific brain hypometabolic patterns at the individual level in the prodromal phase, contributing to the patient's classification. Tau PET is the most accurate biomarker in supporting or excluding the AD diagnosis in aMCI across metabolic subtypes and also predicting the risk of decline.


Subject(s)
Amnesia , Cognitive Dysfunction , Fluorodeoxyglucose F18 , Positron-Emission Tomography , tau Proteins , Humans , Male , Female , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/diagnosis , Aged , tau Proteins/metabolism , Amnesia/diagnostic imaging , Amnesia/metabolism , Prognosis , Aged, 80 and over , Middle Aged , Disease Progression , Brain/diagnostic imaging , Brain/metabolism , Biomarkers/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Alzheimer Disease/diagnosis , Follow-Up Studies
13.
Cortex ; 173: 283-295, 2024 04.
Article in English | MEDLINE | ID: mdl-38442567

ABSTRACT

Evidence suggests that some patients with isolated hippocampal damage appear to present with selective preservation of unfamiliar face recognition relative to other kinds of visual test stimuli (e.g., words). Bird and Burgess (2008) formulated a review and secondary analysis of a group of 10 cases all tested on a clinical assessment of word and face recognition memory (RMT, Warrington, 1984), which confirmed the key memory dissociation at the group level. The current work provides an updated secondary analysis of such cases with a larger published sample (N = 52). In addition to group-level analyses, we also re-evaluate evidence using a single case statistical approach (Crawford & Garthwaite, 2005), enabling us to determine how many would make criteria for a 'classical dissociation' (Crawford, Garthwaite, & Gray, 2003). Overall, group-level analyses indicated the key pattern of significant differences confined to words was limited to small control sample comparisons. When using the large control sample provided by Bird and Burgess (2008), hippocampal cases as a group were significantly poorer for both classes of items. Furthermore, our single-case approach indicated few had a performance pattern of a relative difference across face > word categories that would meet statistical significance; namely within individual differences across categories that would warrant a significant 'classical dissociation'. Moreover, these analyses also found several cases with a 'classical dissociation' in the reverse direction: namely preserved recognition of words. Such analyses serve to demonstrate the need for a more conservative statistical approach to be undertaken when reporting selective 'preservation' of a category in recognition memory. Whilst material specificity has important implications for understanding the role of the hippocampus in memory, our results highlight the need for statistical methods to be unquestionably rigorous before any claims are made. Lastly, we highlight other methodological issues critical to group analyses and make suggestions for future work.


Subject(s)
Facial Recognition , Humans , Recognition, Psychology , Amnesia , Hippocampus , Individuality , Pattern Recognition, Visual
14.
Behav Brain Res ; 465: 114963, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38499158

ABSTRACT

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Rats , Animals , Lisdexamfetamine Dimesylate/therapeutic use , Dextroamphetamine , Treatment Outcome , Attention Deficit Disorder with Hyperactivity/drug therapy , Amnesia/chemically induced , Central Nervous System Stimulants/pharmacology , Double-Blind Method
15.
Brain Inj ; 38(2): 142-149, 2024 01 28.
Article in English | MEDLINE | ID: mdl-38328966

ABSTRACT

OBJECTIVE: The aim of this scoping review was to identify behavioral disturbances exhibited by patients in post-traumatic amnesia (PTA). While behavioral disturbances are common in PTA, research into their presentation and standardized measures for their assessment are limited. DESIGN: The study protocol was registered with PROSPERO (CRD42021268275). A scoping review of databases was performed according to pre-determined criteria on 29 July 2021 and updated on 13 July 2022. A conventional content analysis was used to examine and categorize behavioral disturbances. RESULTS: Thirty papers met the inclusion criteria, of which 27 reported observations and/or scores obtained on behavioral scales, and 3 on clinician interviews and surveys. None focused exclusively on children. Agitation was the most frequently assessed behavior, and Agitated Behavior Scale was the most used instrument. Content analysis, however, bore eight broad behavioral categories: disinhibition, agitation, aggression, lability, lethargy/low mood, perceptual disturbances/psychotic symptoms, personality change and sleep disturbances. CONCLUSION: Our study revealed that while standardized assessments of behavior of patients in PTA are often limited to agitation, clinical descriptions include a range of behavioral disturbances. Our study highlights a significant gap in the systematic assessment of a wide range of behavioral disturbances observed in PTA.


Subject(s)
Brain Injuries, Traumatic , Problem Behavior , Child , Humans , Amnesia/etiology , Amnesia/diagnosis , Amnesia, Retrograde , Anxiety , Aggression
17.
Metab Brain Dis ; 39(4): 589-609, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38351421

ABSTRACT

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.


Subject(s)
Amnesia , Curcumin , Disease Models, Animal , Nanocapsules , Animals , Curcumin/pharmacology , Curcumin/administration & dosage , Curcumin/therapeutic use , Mice , Male , Amnesia/drug therapy , Amnesia/chemically induced , Oxidative Stress/drug effects , Scopolamine
18.
Brain Res ; 1829: 148791, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38307153

ABSTRACT

BACKGROUND: The onset and pathology of sporadic Alzheimer's disease (sAD) seem to be affected by both sex and genetic mechanisms. Evidence supports that the high prevalence of sAD in women, worldwide, may be attributed to an interplay among aging, sex, and lifestyle, influenced by genetics, metabolic changes, and hormones. Interestingly, epigenetic mechanisms such as microRNAs (miRNAs), known as master regulators of gene expression, may contribute to this observed sexual dimorphism in sAD. OBJECTIVES: To investigate the potential impact of sex-associated miRNAs on processes manifesting sAD pathology, as described by the Tau-driven Adverse Outcome Pathway (AOP) leading to memory loss. METHODS: Using publicly available human miRNA datasets, sex-biased miRNAs, defined as differentially expressed by sex in tissues possibly affected by sAD pathology, were collected. In addition, sex hormone-related miRNAs were also retrieved from the literature. The compiled sex-biased and sex hormone-related miRNAs were further plugged into the dysregulated processes of the Tau-driven AOP for memory loss. RESULTS: Several miRNAs, previously identified as sex-associated, were implicated in dysregulated processes associated with the manifestation of sAD pathology. Importantly, the described pathology processes were not confined to a particular sex. A mechanistic-based approach utilizing miRNAs was adopted in order to elucidate the link between sex and biological processes potentially involved in the development of memory loss. CONCLUSIONS: The identification of sex-associated miRNAs involved in the early processes manifesting memory loss may shed light to the complex molecular mechanisms underlying sAD pathogenesis in a sex-specific manner.


Subject(s)
Alzheimer Disease , MicroRNAs , Male , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Alzheimer Disease/metabolism , Aging , Amnesia , Gonadal Steroid Hormones
19.
J Neurosci ; 44(14)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38351000

ABSTRACT

Research on the role of the hippocampus in memory acquisition has generally focused on active learning. But to understand memory, it is at least as important to understand processes that happen offline, during both wake and sleep. In a study of patients with amnesia, we previously demonstrated that although a functional hippocampus is not necessary for the acquisition of procedural motor memory during training session, it is required for its offline consolidation during sleep. Here, we investigated whether an intact hippocampus is also required for the offline consolidation of procedural motor memory while awake. Patients with amnesia due to hippocampal damage (n = 4, all male) and demographically matched controls (n = 10, 8 males) trained on the finger tapping motor sequence task. Learning was measured as gains in typing speed and was divided into online (during task execution) and offline (during interleaved 30 s breaks) components. Amnesic patients and controls showed comparable total learning, but differed in the pattern of performance improvement. Unlike younger adults, who gain speed across breaks, both groups gained speed only while typing. Only controls retained these gains over the breaks; amnesic patients slowed down and compensated for these losses during subsequent typing. In summary, unlike their peers, whose motor performance remained stable across brief breaks in typing, amnesic patients showed evidence of impaired access to motor procedural memory. We conclude that in addition to being necessary for the offline consolidation of motor memories during sleep, the hippocampus maintains access to motor memory across brief offline periods during wake.


Subject(s)
Memory Consolidation , Psychomotor Performance , Adult , Humans , Male , Motor Skills , Memory , Sleep , Amnesia , Hippocampus
20.
J Neurosci ; 44(8)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38228367

ABSTRACT

Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.


Subject(s)
Amnesia , Memory , Male , Mice , Female , Animals , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Memory/physiology , Neuronal Plasticity/physiology , Hippocampus/physiology , Mice, Transgenic
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