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1.
J Chem Neuroanat ; 119: 102043, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808256

RESUMO

The purpose of this study was to highlight the possible effects on the hippocampus of the electromagnetic field (EMF) emitted by mobile phones, and to investigate whether these potential effects can be reduced using various antioxidant substances. Twenty-seven female Wistar albino rats were divided into nine equal groups, each containing three pregnant rats aged 8-10 weeks and weighing 200-250 gr. The EMF groups were exposed to 900 Megahertz (MHz) EMF for 1 h (hr) a day for 21 days. No EMF exposure was applied to the Cont and also the groups given only Garcinia kola (GK), Momordica charantia (MC), and thymoquinone (TQ). The Sham group was kept in the polycarbonate EMF exposure system, but was not exposed to EMF. Four weeks after birth, rat pups were subjected to behavioural tests. Brain tissue samples were evaluated using histological, stereological, functional, and immunohistochemical methods. The numbers of pyramidal neurons in the rat cornu ammonis (CA) were determined using the optical fractionator method. Superoxide dismutase (SOD) and catalase (CAT) enzyme activities in the blood samples were also evaluated. The analysis data indicated that total pyramidal neuron numbers were decreased significantly in the CA of the EMF (1 hr) group (p < 0.01). Our results also showed that the protective effect of MC was more potent than that of the other antioxidant substances (p < 0.01). A 900 MHz EMF can cause deleterious changes in the brain. It can also be suggested that GK, MC and TQ are capable of reducing these adverse effects.


Assuntos
Telefone Celular , Campos Eletromagnéticos , Animais , Campos Eletromagnéticos/efeitos adversos , Feminino , Hipocampo/patologia , Gravidez , Células Piramidais , Ratos , Ratos Wistar
2.
Alzheimers Res Ther ; 14(1): 122, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057586

RESUMO

BACKGROUND: Subjective cognitive decline (SCD) is a putative Alzheimer's disease (AD) precursor without objective neuropsychological deficits. The hippocampus plays an important role in cognitive function and emotional responses and is generally aberrant in SCD. However, previous studies have mainly focused on static functional connectivity (sFC) by resting-state functional magnetic resonance imaging (fMRI) in SCD individuals, and it remains unclear whether hippocampal dynamic functional connectivity (dFC) changes exist in SCD and whether those changes are associated with subtle changes in cognitive function or affect. METHODS: Seventy SCD patients and 65 healthy controls were recruited. Demographic data, comprehensive neuropsychology assessments, and resting-state fMRI data were collected. The bilateral anterior and posterior hippocampi were selected as seeds to investigate the static and dynamic functional connectivity alterations in SCD. RESULTS: Compared to healthy controls, subjects with SCD exhibited: (1) decreased sFC between the left caudal hippocampus and left precuneus; (2) decreased dFC variability between the bilateral caudal hippocampus and precuneus; (3) increased dFC variability between the bilateral rostral hippocampus and caudate nucleus; and (4) increased dFC variability between the left rostral hippocampus and left olfactory cortex. Additionally, the attention scores were positively correlated with dFC variability between the left posterior hippocampus and left precuneus, and the dFC variability between the bilateral anterior hippocampus and caudate nucleus was positively correlated with depression scores and negatively correlated with global cognition scores. CONCLUSION: SCD individuals exhibited abnormal sFC and dFC in the anterior-posterior hippocampus, and abnormal dFC was more widespread than abnormal sFC. A combination of sFC and dFC provides a new perspective for exploring the brain pathophysiological mechanisms in SCD and offers potential neuroimaging biomarkers for the early diagnosis and intervention of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Encéfalo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Testes Neuropsicológicos
3.
Acta Neuropathol Commun ; 10(1): 133, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068646

RESUMO

The pathological hallmarks of Parkinson's disease (PD) are α-synuclein (αSYN)-positive inclusions referred to as Lewy bodies and Lewy neurites, collectively referred to as Lewy-related pathology (LRP). LRP is thought to propagate in an ascending manner throughout the brain as the disease progresses. LRP is visible with histologic methods and is thought to represent a later stage of the disease process, while αSYN oligomers, which are not visible with routine histologic methods, are considered earlier. There is increasing evidence to suggest that αSYN oligomers may be more toxic than visible LRP. Detecting αSYN oligomers requires special techniques, and their distribution and association with clinical features are important research objectives. In this report, we describe the distribution of αSYN oligomers in multiple cortical and subcortical regions of PD using a proximity ligation assay (PLA). We observe widespread distribution of αSYN oligomers with PLA and more restricted distribution of LRP with αSYN immunohistochemistry. The distribution of αSYN oligomers differed from LRP in that αSYN oligomer burden was significantly greater in the neocortex, while LRP was greater in vulnerable subcortical regions, including the brainstem. We also found that cognitive impairment was associated with αSYN oligomers in the hippocampus. These results suggest that αSYN oligomers may be widely distributed in PD early in the disease process and that they may contribute to cognitive impairment in PD.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Hipocampo/patologia , Humanos , Corpos de Lewy/metabolismo , Neurônios/metabolismo , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo
4.
Transl Psychiatry ; 12(1): 388, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114184

RESUMO

Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies.Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Esquizofrenia , Adulto , Estudos Transversais , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Tamanho do Órgão , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
5.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35955450

RESUMO

Adolescence is a developmental epoch characterized by massive neural circuit remodeling; thus, the brain is particularly vulnerable to environmental influences during this period. Excessive high-fat diet (HFD) consumption, which is very common among adolescents, has long been recognized as a potent risk factor for multiple mood disorders, including depression and anxiety. However, the precise mechanisms underlying the influences of HFD consumption in adolescence on emotional health are far from clear. In the present study, C57BL/6 mice were fed a control diet (CD) or HFD for about 4 weeks from postnatal day (P) 28 to P60, spanning most of the adolescence period, and then subjected to behavioral assessments and histological examinations. HFD mice exhibited elevated levels of depression and anxiety, decreased hippocampal neurogenesis, and excessive microglial activation in the ventral hippocampus. Furthermore, in HFD-fed mice, microglia showed increased DCX+ inclusions, suggesting aberrant microglial engulfment of newborn neurons in HFD-fed adolescents. To our knowledge, this is the first observation suggesting that the negative effects of HFD consumption in adolescence on emotion and neuroplasticity may be attributed at least in part to aberrant microglial engulfment of nascent neurons, extending our understanding of the mechanism underlying HFD-related affective disorders in young people.


Assuntos
Dieta Hiperlipídica , Microglia , Animais , Dieta Hiperlipídica/efeitos adversos , Emoções , Hipocampo/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Neurogênese/fisiologia
6.
Handb Clin Neurol ; 187: 407-427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35964985

RESUMO

Neuropathological examination of the temporal lobe provides a better understanding and management of a wide spectrum of diseases. We focused on inflammatory diseases, epilepsy, and neurodegenerative diseases, and highlighted how the temporal lobe is particularly involved in those conditions. Although all these diseases are not specific or restricted to the temporal lobe, the temporal lobe is a key structure to understand their pathophysiology. The main histological lesions, immunohistochemical markers, and molecular alterations relevant for the neuropathological diagnostic reasoning are presented in relation to epidemiology, clinical presentation, and radiological findings. The inflammatory diseases section addressed infectious encephalitides and auto-immune encephalitides. The epilepsy section addressed (i) susceptibility of the temporal lobe to epileptogenesis, (ii) epilepsy-associated hippocampal sclerosis, (iii) malformations of cortical development, (iv) changes secondary to epilepsy, (v) long-term epilepsy-associated tumors, (vi) vascular malformations, and (vii) the absence of histological lesion in some epilepsy surgery samples. The neurodegenerative diseases section addressed (i) Alzheimer's disease, (ii) the spectrum of frontotemporal lobar degeneration, (iii) limbic-predominant age-related TDP-43 encephalopathy, and (iv) α-synucleinopathies. Finally, inflammatory diseases, epilepsy, and neurodegenerative diseases are considered as interdependent as some pathophysiological processes cross the boundaries of this classification.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Doenças Neurodegenerativas , Epilepsia/epidemiologia , Epilepsia/patologia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Humanos , Lobo Temporal/patologia
7.
Crit Rev Eukaryot Gene Expr ; 32(5): 11-20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35993941

RESUMO

MicroRNAs are reported to correlate with synaptic plasticity and exert functions in Alzheimer's disease (AD) pathogenesis. miR-369-5p is identified to be upregulated in AD mice. This study explores miR-369-5p roles in synaptic plasticity in hippocampal cells and in an AD mouse model. Wild-type C57BL/6J mice (6 months) were trained in a well-established object memory task. Two identical objects were presented to mice for 10 min. miR-369-5p expression in hippocampus, cortex, and striatum, and in hippocampal cells was measured by reverse transcription quantitative polymerase chain reaction. Then, 0.2 mM glycine and 100 nM amyloid-beta oligomers were used to treat primary hippocampal cells. The levels of plasticity-related proteins in hippocampal cells and hippocampus were evaluated by Western blotting. Object location memory (OLM) of 3xTg-AD mice was tested in an OLM protocol at 13 months of age. In this study, learning increased miR-369-5p level in the hippocampus. The increased levels of plasticity-related proteins induced by chemical long-term potentiation were inhibited by miR-369-5p inhibitors in hippocampal cultures. miR-369-5p upregulation rescued the Aßo-induced suppression in the levels of plasticity-related proteins in hippocampal cultures. miR-369-5p elevation increased GluA1 and GluA2 protein levels and rescued OLM impairment in an AD mouse model. In conclusion, miR-369-5p positively regulates the levels of plasticity-related proteins in hippocampal cultures and in an AD mice model.


Assuntos
Doença de Alzheimer , MicroRNAs , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo
8.
Hippocampus ; 32(9): 660-678, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35916343

RESUMO

Pathological changes in the medial temporal lobe (MTL) are found in the early stages of Alzheimer's disease (AD) and aging. The earliest pathological accumulation of tau colocalizes with the areas of the MTL involved in object processing as part of a wider anterolateral network. Here, we sought to assess the diagnostic potential of memory for object locations in iVR environments in individuals at high risk of AD dementia (amnestic mild cognitive impairment [aMCI] n = 23) as compared to age-related cognitive decline. Consistent with our primary hypothesis that early AD would be associated with impaired object location, aMCI patients exhibited impaired spatial feature binding. Compared to both older (n = 24) and younger (n = 53) controls, aMCI patients, recalled object locations with significantly less accuracy (p < .001), with a trend toward an impaired identification of the object's correct context (p = .05). Importantly, these findings were not explained by deficits in object recognition (p = .6). These deficits differentiated aMCI from controls with greater accuracy (AUC = 0.89) than the standard neuropsychological tests. Within the aMCI group, 16 had CSF biomarkers indicative of their likely AD status (MCI+ n = 9 vs. MCI- n = 7). MCI+ showed lower accuracy in the object-context association than MCI- (p = .03) suggesting a selective deficit in object-context binding postulated to be associated with anterior-temporal areas. MRI volumetric analysis across healthy older participants and aMCI revealed that test performance positively correlates with lateral entorhinal cortex volumes (p < .05) and hippocampus volumes (p < .01), consistent with their hypothesized role in binding contextual and spatial information with object identity. Our results indicate that tests relying on the anterolateral object processing stream, and in particular requiring successful binding of an object with spatial information, may aid detection of pre-dementia AD due to the underlying early spread of tau pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico por imagem , Demência/complicações , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos
9.
Eur Radiol ; 32(10): 6965-6976, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35999372

RESUMO

OBJECTIVES: Hippocampal radiomic features (HRFs) can serve as biomarkers in Alzheimer's disease (AD). However, how different hippocampal segmentation methods affect HRFs in AD is still unknown. The aim of the study was to investigate how different segmentation methods affect HRF accuracy in AD analysis. METHODS: A total of 1650 subjects were identified from the Alzheimer's Disease Neuroimaging Initiative database (ADNI). The mini-mental state examination (MMSE) and Alzheimer's disease assessment scale (ADAS-cog13) were also adopted. After calculating the HRFs of intensity, shape, and textural features from each side of the hippocampus in structural magnetic resonance imaging (sMRI), the consistency of HRFs calculated from 7 different hippocampal segmentation methods was validated, and the performance of machine learning-based classification of AD vs. normal control (NC) adopting the different HRFs was also examined. Additional 571 subjects from the European DTI Study on Dementia database (EDSD) were to validate the consistency of results. RESULTS: Between different segmentations, HRFs showed a high measurement consistency (R > 0.7), a high significant consistency between NC, mild cognitive impairment (MCI), and AD (T-value plot, R > 0.8), and consistent significant correlations between HRFs and MMSE/ADAS-cog13 (p < 0.05). The best NC vs. AD classification was obtained when the hippocampus was sufficiently segmented by primitive majority voting (threshold = 0.2). High consistent results were reproduced from independent EDSD cohort. CONCLUSIONS: HRFs exhibited high consistency across different hippocampal segmentation methods, and the best performance in AD classification was obtained when HRFs were extracted by the naïve majority voting method with a more sufficient segmentation and relatively low hippocampus segmentation accuracy. KEY POINTS: • The hippocampal radiomic features exhibited high measurement/statistical/clinical consistency across different hippocampal segmentation methods. • The best performance in AD classification was obtained when hippocampal radiomics were extracted by the naïve majority voting method with a more sufficient segmentation and relatively low hippocampus segmentation accuracy.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos
10.
Exp Gerontol ; 166: 111890, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35843348

RESUMO

OBJECTIVE: There is a shred of growing evidence demonstrating that diabetic patients are at higher risk of developing Alzheimer's disease compared to the general population. The previous investigation showed the protective effect of metformin for delaying dementia in diabetic patients. However, there are limited data on the effect of metformin on structural changes. This study aims to investigate the effect of metformin on hippocampal and cortical volumes in non-demented diabetic individuals. METHOD: We entered 157 non-demented diabetic subjects including 89 mild cognitive impairment (MCI), and 68 cognitively healthy individuals from Alzheimer's disease Neuroimaging Initiative (ADNI) which were then categorized as metformin users and non-users. We used the ANCOVA model for measuring the association between metformin use and hippocampal and cortical volumes. RESULTS: Among 157 subjects with a mean age of 71.8 (±7.7) included in this study, 76 individuals were stratified as metformin users. Results of the univariate model indicate that metformin users had a higher right (p = 0.003) and left parietal lobe volume (p = 0.004). Moreover, the volume of left cingulate was higher in those who used metformin compared to those not used it (p = 0.027). Our results were also significant for the right frontal lobe and indicated that metformin users had higher volume (p = 0.035). There were no significant differences in the hippocampus, occipital, and temporal regions. CONCLUSION: Our findings showed the protective effects of metformin on brain volumes in non-demented elderly individuals with diabetes. Comparing the groups show strong enough results regarding the lower atrophy in metformin users.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus , Metformina , Idoso , Doença de Alzheimer/patologia , Atrofia/patologia , Encéfalo/patologia , Diabetes Mellitus/tratamento farmacológico , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Metformina/uso terapêutico
11.
J Affect Disord ; 314: 325-332, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878837

RESUMO

BACKGROUND: Bipolar disorder (BD) is a strongly familial psychiatric disorder associated with white matter (WM) brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about WM trajectories in those at increased genetic risk. METHODS: Diffusion magnetic resonance imaging (dMRI) data were acquired at baseline and after two years in 91 unaffected individuals with a first-degree relative with bipolar disorder (HR), and 85 individuals with no family history of mental illness (CON). All participants were aged between 12 and 30 years at baseline. We examined longitudinal change in Fractional Anisotropy (FA) using tract-based spatial statistics (TBSS). RESULTS: Compared to the CON group, HR participants showed a significant increase in FA in the right cingulum (hippocampus) (CGH) over a two-year period (p < .05, FDR corrected). This effect was more pronounced in HR individuals without a lifetime diagnosis of a mood disorder than those with a mood disorder. LIMITATIONS: While our study is well powered to achieve the primary objectives, our sub-group analyses were under powered. CONCLUSIONS: In one of the very few longitudinal neuroimaging studies of young people at high risk for BD, this study reports novel evidence of atypical white matter development in HR individuals in a key cortico-limbic tract involved in emotion regulation. Our findings also suggest that this different white matter developmental trajectory may be stronger in HR individuals without affective psychopathology. As such, increases in FA in the right CGH of HR participants may be a biomarker of resilience to mood disorders.


Assuntos
Transtorno Bipolar , Substância Branca , Adolescente , Adulto , Anisotropia , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/genética , Criança , Imagem de Tensor de Difusão/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Rede Nervosa/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
12.
Nature ; 607(7919): 527-533, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794479

RESUMO

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.


Assuntos
Envelhecimento , Hipocampo , Longevidade , Neurogênese , Neurônios , Adulto , Envelhecimento/genética , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Proliferação de Células , Giro Denteado/citologia , Giro Denteado/patologia , Perfilação da Expressão Gênica , Hipocampo/citologia , Hipocampo/patologia , Humanos , Longevidade/genética , Aprendizado de Máquina , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Análise de Célula Única , Transcrição Genética
13.
Twin Res Hum Genet ; 25(3): 129-139, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35791873

RESUMO

The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%-72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%-77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%-16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).


Assuntos
Hipocampo , Imageamento por Ressonância Magnética , Irmãos , Gêmeos , Adulto , Encéfalo , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Gêmeos/genética , Adulto Jovem
14.
PLoS One ; 17(7): e0272365, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35905135

RESUMO

This study investigates visuospatial memory in patients with unilateral lesions of the temporal lobe and the hippocampus resulting from surgery to treat drug-resistant epilepsy. To detect impairments of visuospatial memory in these individuals, a memory test should be specific to episodic memory, the type of memory in which the hippocampus is crucially involved. However, most known visuospatial memory tests do not focus on episodic memory. We hypothesized that a new sequential visuospatial memory test, which has been previously developed and applied only in healthy subjects, might be suitable to fill this gap. The test requires the subject to reproduce a memorized sequence of target locations in ordered recall by typing on a blank graphics tablet. The length of the memorized sequence extended successively after repeated presentation of a sequence of 20 target positions. The test was done twice on day one and again after one week. Visual working memory was tested with the Corsi block-tapping task. The performance in the new test was also related to the performance of the patients in the standard test battery of the neuropsychological examination in the clinical context. Thirteen patients and 14 controls participated. Patients showed reduced learning speed in the new sequential visuospatial memory task. Right-sided lesions induced stronger impairments than left-sided lesions. After one week, retention was reduced in the patients with left-sided lesions. The performance of the patients in commonly used tests of the neuropsychological standard battery did not differ compared to healthy subjects, whereas the new test allowed discrimination between patients and controls at a high correct-decision rate of 0.89. The Corsi block-span of the patients was slightly shorter than that of the controls. The results suggest that the new test provides a specific investigation of episodic visuospatial memory. Hemispheric asymmetries were consistent with the general hypothesis of right hemispheric dominance in visuospatial processing.


Assuntos
Epilepsia do Lobo Temporal , Lobo Temporal , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Humanos , Memória de Curto Prazo , Testes Neuropsicológicos , Lobo Temporal/patologia
15.
PLoS One ; 17(7): e0270795, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35830443

RESUMO

Hippocampal subfield atrophy is a prime structural change in the brain, associated with cognitive aging and neurodegenerative diseases such as Alzheimer's disease. Recent developments in genome-wide association studies (GWAS) have identified genetic loci that characterize the risk of hippocampal volume loss based on the processes of normal and abnormal aging. Polygenic risk scores are the genetic proxies mimicking the genetic role of the pre-existing vulnerabilities of the underlying mechanisms influencing these changes. Discriminating the genetic predispositions of hippocampal subfield atrophy between cognitive aging and neurodegenerative diseases will be helpful in understanding the disease etiology. In this study, we evaluated the polygenic risk of Alzheimer's disease (AD PGRS) for hippocampal subfield atrophy in 1,086 individuals (319 cognitively normal (CN), 591 mild cognitively impaired (MCI), and 176 Alzheimer's disease dementia (ADD)). Our results showed a stronger association of AD PGRS effect on the left hemisphere than on the right hemisphere for all the hippocampal subfield volumes in a mixed clinical population (CN+MCI+ADD). The subfields CA1, CA4, hippocampal tail, subiculum, presubiculum, molecular layer, GC-ML-DG, and HATA showed stronger AD PGRS associations with the MCI+ADD group than with the CN group. The subfields CA3, parasubiculum, and fimbria showed moderately higher AD PGRS associations with the MCI+ADD group than with the CN group. Our findings suggest that the eight subfield regions, which were strongly associated with AD PGRS are likely involved in the early stage ADD and a specific focus on the left hemisphere could enhance the early prediction of ADD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Atrofia/genética , Atrofia/patologia , Estudo de Associação Genômica Ampla , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética
16.
Acta Neurobiol Exp (Wars) ; 82(2): 170-178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35833816

RESUMO

Acetaminophen is one of the most widely used over­the­counter drugs worldwide for the treatment of pain and fever. Although acetaminophen use is known to impair hippocampus­related learning and memory, its effect on anxiety is not clear. Insulin­like growth factor­1 (IGF­1) and matrix metalloproteinase­2 (MMP2) are important for cellular survival, maintenance and tissue integrity. The aim of this study was to investigate the dose­dependent effects of acetaminophen on anxiety levels as well as on hippocampus, prefrontal cortex and liver tissue. Doses of 100, 200 and 400 mg/kg acetaminophen were administered to male Sprague Dawley rats for 11 days and anxiety tests were conducted on the last day. Twenty­four hours after the last acetaminophen administration, all animals were sacrificed and hippocampus, prefrontal cortex and liver tissues were removed for analyses. Hippocampal IGF­1 and MMP2 levels were shown to decrease only at the highest dose of acetaminophen, which was accompanied by pathological changes in histology. The prefrontal cortex was not affected. Behavioral analyses also did not indicate changes in anxiety levels in the rats. Liver IGF­1 and MMP2 levels decreased in all experimental groups. Serum alanine aminotransferase and aspartate aminotransferase levels increased in the 200 mg/kg and 400 mg/kg acetaminophen groups. Our findings showed that varying doses of acetaminophen did not affect the prefrontal cortex or anxiety levels. Further research is needed to elucidate the hippocampal and hepatic protective roles of IGF­1 and MMP2 in acetaminophen toxicity and their potential use in therapeutic approaches.


Assuntos
Acetaminofen , Hipocampo , Metaloproteinase 2 da Matriz , Acetaminofen/toxicidade , Alanina Transaminase , Animais , Ansiedade/tratamento farmacológico , Aspartato Aminotransferases , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Fator de Crescimento Insulin-Like I , Masculino , Ratos , Ratos Sprague-Dawley
17.
Neuropsychologia ; 174: 108311, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810880

RESUMO

Social network size has been associated with complex socio-cognitive processes (e.g., memory, perspective taking). Supporting this idea, recent neuroimaging studies in healthy adults have reported a relationship between social network size and brain volumes in regions related to memory and social cognition (e.g., hippocampus, amygdala). Lesion-deficit studies in neurological patients are rare and have been inconclusive due to differences in participant sampling and measurement. The present study uses a multiple case study approach. We investigated patients with focal damage to the hippocampus and/or amygdala (two neural structures thought to be critical for social networks), and examined the patients' social network size, loneliness, and life satisfaction relative to a non-injured comparison group. Patients with amygdalar damage had smaller social networks and reported higher levels of loneliness and lower life satisfaction, on average, than comparison participants. Patients with damage to the hippocampus reported more friends than the comparison participants, but did not differ in their ratings of loneliness or life satisfaction. This lesion study offers new evidence that the amygdala is critical for social networks, life satisfaction, and reduced loneliness.


Assuntos
Tonsila do Cerebelo , Hipocampo , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Rede Social
18.
Sci Rep ; 12(1): 12008, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835801

RESUMO

Several studies have highlighted the value of diffusion tensor imaging (DTI) with strong diffusion weighting to reveal white matter microstructural lesions, but data in gray matter (GM) remains scarce. Herein, the effects of b-values combined with different numbers of diffusion-encoding directions (NDIRs) on DTI metrics to capture the normal hippocampal microstructure and its early alterations were investigated in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis [EAE]). Two initial DTI datasets (B2700-43Dir acquired with b = 2700 s.mm-2 and NDIR = 43; B1000-22Dir acquired with b = 1000 s.mm-2 and NDIR = 22) were collected from 18 normal and 18 EAE mice at 4.7 T. Three additional datasets (B2700-22Dir, B2700-12Dir and B1000-12Dir) were extracted from the initial datasets. In healthy mice, we found a significant influence of b-values and NDIR on all DTI metrics. Confronting unsupervised hippocampal layers classification to the true anatomical classification highlighted the remarkable discrimination of the molecular layer with B2700-43Dir compared with the other datasets. Only DTI from the B2700 datasets captured the dendritic loss occurring in the molecular layer of EAE mice. Our findings stress the needs for both high b-values and sufficient NDIR to achieve a GM DTI with more biologically meaningful correlations, though DTI-metrics should be interpreted with caution in these settings.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Substância Branca , Animais , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão/métodos , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/diagnóstico por imagem , Encefalomielite Autoimune Experimental/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Camundongos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
19.
Neurol Sci ; 43(10): 5951-5958, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35849197

RESUMO

INTRODUCTION: Transient global amnesia (TGA) is defined as a sudden and transient episode of memory loss and accompanied by temporal disorientation. However, the mechanism by which time distortion occurs is not clearly elucidated yet. METHODS: Between March 2019 and November 2020, we subjected 30 TGA patients to several time perception tasks and analyzed their magnetic resonance image (MRI) scans and compared the results with age- and sex-matched control group. RESULTS: Among the 60 recruited subjects (64.5 ± 6.3 years), 70% were women. Fourteen patients had only anterograde amnesia. Furthermore, 46% of the patients with TGA (n = 14) had a history of Valsalva maneuver, and 70% of the patients (n = 21) had a pre-attack stress factor. The MRI scans of 14 patients (46.67%) showed hippocampal hyperintensity. With regard to the time production task, patients with TGA exhibited shorter times in all trials compared with their counterparts (5 s, 4.90 ± 1.16 vs. 5.53 ± 0.87; p value = 0.02: 15 s, 12.18 ± 4.55 vs. 14.42 ± 2.54; p value = 0.021). For the time comparison task, the number of correct answers given by patients with TGA was significantly lesser than that given by the control group (6.07 ± 1.23 vs. 6.90 ± 1.24; p value = 0.006). CONCLUSIONS: This is the first study to invesgating an altered time perception in patients with TGA. Although the exact neurophysiological mechanism remains unclear, our findings could aid in the elucidation of brain function across specific time frames.


Assuntos
Amnésia Global Transitória , Percepção do Tempo , Amnésia , Amnésia Global Transitória/diagnóstico por imagem , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino
20.
Brain Behav ; 12(8): e32723, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35861689

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease. Progressive depletion of the brain and spinal cord tissue appears at the onset of the disease. Several studies have shown the increased size of the ventricles of the brain and decreases in the area of the corpus callosum and the width of the brain. Other important symptoms of this disease are cognitive, learning, and memory disorders. AIM: The aim of this study was to compare morphometric, histological, and functional changes in the demyelination model in both sexes. MATERIALS AND METHODS: In this experimental study, male and female Wistar rats were studied in four experimental groups. Demyelination was induced by the injection of ethidium bromide in the ventricular region. The chronic effect of demyelination on spatial memory, movement, and coordination was investigated using the Morris Water Maze (MWM), and clinical and balance beam tests, respectively. Myelin degradation, cell death and neurogenesis were estimated using Luxol Fast Blue staining and immunohistochemistry (Caspase-3 and Nestin markers). In addition, morphometric findings were recorded for the brain and hippocampus (weight, volume, length, width). RESULT: Demyelination increased the time and distance index and decreased the residence time in the target quarter in the water maze test (p < .001). It also increases the neuromuscular and modified neurological severity score (p < .01). Demyelination increases caspase-3 (p < .05) expression and decreases Nestin expression (p < .001), which are directly related to the extent of damage. CONCLUSION: This study showed an interaction between hippocampal structural and functional networks in explaining spatial learning and memory in the early stages of MS.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Animais , Caspase 3 , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Feminino , Hipocampo/patologia , Masculino , Esclerose Múltipla/patologia , Nestina , Ratos , Ratos Wistar , Memória Espacial
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