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1.
Exp Neurol ; 359: 114260, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36404463

RESUMO

Traumatically injured brain functional connectivity (FC) is altered in a region-dependent manner with some regions functionally disconnected while others are hyperconnected after experimental TBI. Remote, homotopic cortical regions become hyperexcitable after injury, and we hypothesize that this results in increased trans-hemispheric cortical inhibition, preventing reorganization of the primary injured hemisphere. Previously we have shown that temporary silencing the contralesional cortex at 1wk normalizes affected forelimb behavioral use, but not at 4wks. To investigate the potential mechanism for this and to determine whether this occurs due to restoration of afferent pathway FC, and/or reorganization of brain circuits, we probed forelimb circuit function with sensorimotor task-evoked-fMRI, resting state fMRI seed-based analysis, and exploratory structural equation modelling (SEM) of directed causal connections due to forelimb task at 1 and 4wks post-injury after temporary, contralateral silencing with intraparenchymal injection of muscimol versus vehicle, as well as from sham rats. As predicted, silencing at 1wk and 4wks post-injury decimated the contralesional cortical forelimb map evoked by stimulation of the opposite, unaffected forelimb compared to vehicle-injected injured rats indicating the success of the intervention. Surprisingly however, this also resulted in activation of the pericontused cortex ipsilateral to the stimulated forelimb at 1wk, yet this same region could not be activated by directly stimulating the opposite, injury-affected forelimb. Underpinning this were significant increases in interhemispheric FC at the level of the cortex but decreases within subcortical regions. Causal SEM analysis confirmed increased corticothalamic connectivity and suggested changes from and to bilateral thalamus are important for the effect. At 4wks post-injury only cortical increases in FC were found in response to silencing indicating a less flexible brain, and ipsilesional cortex evoked activity was mostly absent. The absence of a reinstatement of ipsilesional evoked activity through normal pathways by temporary neuromodulation despite prior data showing behavioral improvements under the same conditions, indicates that while the pericontused cortex does retain function initially after injury, it is too functionally disconnected to be controlled by normal afferent input. More significant alterations in cross-brain FC during neuromodulation at 1wk compared to 4wk post-injury, suggest that more distributed brain activity accounts for prior behavior improvements in sensorimotor function, and that hemispheric imbalance in function is causally involved in early loss of sensorimotor function in this TBI model.


Assuntos
Membro Anterior , Extremidade Superior , Animais , Ratos , Encéfalo , Vias Aferentes , Muscimol
2.
Artigo em Inglês | MEDLINE | ID: mdl-36418179

RESUMO

BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 × 10-5) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Estudo de Associação Genômica Ampla , Vitamina D , Encéfalo , Fatores de Risco
3.
Bioorg Chem ; 130: 106261, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399866

RESUMO

In this work, we have investigated the one pot strategy for the Cu(I)-mediated synthesis of new triazoles bearing nitroindazole moieties using different copper catalysts. The biological activity of newly synthesized nitroindazolyltriazoles towards Alzheimer's disease-related targets, namely cholinesterases, monoamine oxidases, and amyloid aggregation, were investigated. Predictions of target affinity, physicochemical parameters, gastrointestinal absorption and brain penetration were achieved by means of in silico tools.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Proteínas Amiloidogênicas , Colinesterases , Encéfalo , Monoaminoxidase
4.
Life Sci Alliance ; 6(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36450447

RESUMO

We recently developed a "Build and Retrieve" cryo-electron microscopy (cryo-EM) methodology, which is capable of simultaneously producing near-atomic resolution cryo-EM maps for several individual proteins from a heterogeneous, multiprotein sample. Here we report the use of "Build and Retrieve" to define the composition of a raw human brain microsomal lysate. From this sample, we simultaneously identify and solve cryo-EM structures of five different brain enzymes whose functions affect neurotransmitter recycling, iron metabolism, glycolysis, axonal development, energy homeostasis, and retinoic acid biosynthesis. Interestingly, malfunction of these important proteins has been directly linked to several neurodegenerative disorders, such as Alzheimer's, Huntington's, and Parkinson's diseases. Our work underscores the importance of cryo-EM in facilitating tissue and organ proteomics at the atomic level.


Assuntos
Elétrons , Microssomos , Humanos , Microscopia Crioeletrônica , Encéfalo , Proteômica
5.
Gene ; 851: 147026, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36332837

RESUMO

Overfeeding (OF) and obesity increase the risk for brain aging and neurodegenerative diseases due to increased oxidative stress and neuroinflammation, which likely contribute to cellular dysfunction. In contrast, caloric restriction (CR) is an intervention known for its effects on extending both life- and health-span. In the current study, the effects on the aging brain of two short-term feeding regimens, OF and CR, were investigated. We applied these diets for 12 weeks to both young and aged zebrafish. We performed protein and mRNA level analysis to examine diet-mediated effects on any potential age-related alterations in the brain. Markers implicated in the regulation of brain aging, cell cycle, proliferation, inflammation, and cytoskeleton were analyzed. The most prominent result observed was a downregulation in the expression levels of the stem cell marker, Sox2, in CR-fed animals as compared to OF-fed fish. Furthermore, our data highlighted significant age-related downregulations in Tp53, Myca, and L-plastin levels. The multivariate analyses of all datasets suggested that as opposed to OF, the adaptive mechanisms increasing lifespan via CR are likely exerting their effects by reinforcing the stem cell pool and downregulating inflammation. The data reveal important therapeutic targets with respect to the state of nutrient uptake for the slowing down of the detrimental effects of aging, resulting in a healthy and extended lifespan, as well as lowering the risk for neurodegenerative disease.


Assuntos
Restrição Calórica , Doenças Neurodegenerativas , Animais , Doenças Neurodegenerativas/metabolismo , Peixe-Zebra/metabolismo , Encéfalo/metabolismo , Envelhecimento/metabolismo , Biomarcadores/metabolismo , Inflamação/metabolismo , Células-Tronco/metabolismo , Proliferação de Células
6.
Neurosci Lett ; 792: 136938, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341925

RESUMO

BACKGROUND: Research on the peptide phoenixin has increased in recent years and greatly widened the known scope of its functions since its discovery in 2013. Involvement of phoenixin has since been shown in anxiety, food intake, reproduction as well as emotional and immunological stress. To further evaluate its involvement in stress reactions, this study aims to investigate the effects of abdominal surgery, a well-established physical stressor, on the activity of phoenixin-immunoreactive brain nuclei. METHODS: Male Sprague-Dawley rats (n = 6/group) were subjected to either an abdominal surgery stress protocol or a sham operation. Animals in the verum group were anesthetized, the abdominal cavity opened and the cecum palpated, followed by closing of the abdomen and recovery. Sham operated animals only received inhalation anesthesia and time for recovery. All animals were subsequently sacrificed and brains processed and evaluated for c-Fos activity as well as phoenixin density. RESULTS: Compared to control, abdominal surgery significantly increased c-Fos activity in the paraventricular nucleus (PVN, 6.4-fold, p < 0.001), the medial part of the nucleus of the solitary tract (mNTS, 3.8-fold, p < 0.001), raphe pallidus (RPa, 3.6-fold, p < 0.001), supraoptic nucleus (SON, 3.2-fold, p < 0.001), ventrolateral medulla (VLM, also called A1C1, 3.0-fold, p < 0.001), dorsal motor nucleus of vagus (DMN, 2.9-fold, p < 0.001), locus coeruleus (LC, 1.8-fold, p < 0.01) and Edinger-Westphal nucleus (EW, 1.6-fold, p < 0.05), while not significantly altering c-Fos activity in the amygdala (CeM, 1.3-fold, p > 0.05). Phoenixin immunoreactivity was not significantly affected by abdominal surgery (p > 0.05). CONCLUSION: The observed abdominal surgery-related increase in activity in phoenixin immunoreactive nuclei compared to sham surgery controls supports the hypothesis of an involvement of phoenixin in stress reactions. Interestingly, various psychological and physical stressors lead to specific changes in activity and immunoreactivity in phoenixin-containing nuclei, giving rise to a stressor-specific involvement of phoenixin.


Assuntos
Núcleo Hipotalâmico Paraventricular , Núcleo Supraóptico , Animais , Ratos , Masculino , Ratos Sprague-Dawley , Núcleo Supraóptico/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Encéfalo/metabolismo
7.
Environ Res ; 216(Pt 2): 114595, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257450

RESUMO

BACKGROUND: Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. OBJECTIVES: To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. METHODS: We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants' home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9-12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. RESULTS: Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). DISCUSSION: APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Alzheimer , Apolipoproteína E4 , Criança , Feminino , Humanos , Gravidez , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Encéfalo , Fatores de Risco , Herança Multifatorial
8.
Magn Reson Med ; 89(2): 665-677, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36253953

RESUMO

PURPOSE: To explore the properties of short-T2 signals in human brain, investigate the impact of various experimental procedures on these properties and evaluate the performance of three-component analysis. METHODS: Eight samples of non-pathological human brain tissue were subjected to different combinations of experimental procedures including D2 O exchange and frozen storage. Short-T2 imaging techniques were employed to acquire multi-TE (33-2067 µs) data, to which a three-component complex model was fitted in two steps to recover the properties of the underlying signal components and produce amplitude maps of each component. For validation of the component amplitude maps, the samples underwent immunohistochemical myelin staining. RESULTS: The signal component representing the myelin bilayer exhibited super-exponential decay with T2,min of 5.48 µs and a chemical shift of 1.07 ppm, and its amplitude could be successfully mapped in both white and gray matter in all samples. These myelin maps corresponded well to myelin-stained tissue sections. Gray matter signals exhibited somewhat different components than white matter signals, but both tissue types were well represented by the signal model. Frozen tissue storage did not alter the signal components but influenced component amplitudes. D2 O exchange was necessary to characterize the non-aqueous signal components, but component amplitude mapping could be reliably performed also in the presence of H2 O signals. CONCLUSIONS: The myelin mapping approach explored here produced reasonable and stable results for all samples. The extensive tissue and methodological investigations performed in this work form a basis for signal interpretation in future studies both ex vivo and in vivo.


Assuntos
Bainha de Mielina , Substância Branca , Humanos , Bainha de Mielina/química , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
9.
Magn Reson Med ; 89(2): 620-635, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36253943

RESUMO

PURPOSE: Design an efficient CEST scheme for exchange-dependent images with high contrast-to-noise ratio. THEORY: Reassembled saturation transfer (REST) signals were defined as Δ $$ \Delta $$ r.Z = r.Zref - r.ZCEST and the reassembled exchange-dependen magnetization transfer ratio r.MTRRex  = r.1/Zref - r.1/ZCEST , utilizing the averages over loosely sampled reference frequency offsets as Zref and over densely sampled target offsets as ZCEST . Using r.MTRRex measured under 2 B1,sat values, exchange rate could be estimated. METHODS: The REST approach was optimized and assessed quantitatively by simulations for various exchange rates, pool concentration, and water T1 . In vivo evaluation was performed on ischemic rat brains at 7 Tesla and human brains at 3 Tesla, in comparison with conventional asymmetrical analysis, Lorentzian difference (LD), an MTRRex_ LD. RESULTS: For a broad choice of Δ ω ref $$ \Delta {\omega}_{ref} $$ ranges and numbers, Δr.Z and r.MTRRex exhibited comparable quantification features with conventional LD and MTRRex _LD, respectively, when B1,sat  ≤ 1 µT. The subtraction of 2 REST values under distinct B1,sat values showed linear relationships with exchange rate and obtained immunity to field inhomogeneity and variation in MT and water T1 . For both rat and human studies, REST images exhibited similar contrast distribution to MTRRex _LD, with superiority in contrast-to-noise ratio and acquisition efficiency. Compared with MTRRex _LD, 2-B1,sat subtraction REST images displayed better resistance to B1 inhomogeneity, with more specific enhanced regions. They also showed higher signals for amide than for nuclear Overhauser enhancement effect in human brain, presumably reflecting the higher increment from faster-exchanging species as B1,sat increased. CONCLUSION: Featuring high contrast-to-noise ratio efficiency, REST could be a practical exchange-dependent approach readily applicable to either retrospective Z-spectra analysis or perspective 6-offset acquisition.


Assuntos
Amidas , Imageamento por Ressonância Magnética , Animais , Humanos , Ratos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Encéfalo/diagnóstico por imagem , Água
12.
Methods Mol Biol ; 2576: 181-188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152186

RESUMO

Autoradiography of radiolabeled GTPγS ([35S]GTPγS) binding is a relevant technique to study the function of G protein-coupled receptors (GPCRs) ex vivo. Here, we describe the protocol for such a method, suitable for investigating CB1 receptor functionality in tissue slices from rodent brains.


Assuntos
Encéfalo , Receptores Acoplados a Proteínas G , Autorradiografia , Encéfalo/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Radioisótopos de Enxofre/metabolismo
13.
Methods Mol Biol ; 2576: 241-247, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152192

RESUMO

Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological effects of this lipid mediator. The final products of AEA cleavage are arachidonic acid and ethanolamine. In the method described herein, FAAH activity is measured through the use of the radioactive substrate [14C-ethanolamine]-AEA and subsequent quantification of the reaction product [14C]-ethanolamine.


Assuntos
Amidoidrolases , Endocanabinoides , Amidoidrolases/metabolismo , Ácido Araquidônico , Encéfalo/metabolismo , Etanolamina , Etanolaminas , Hidrólise
14.
Methods Mol Biol ; 2576: 407-424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152206

RESUMO

Conventional techniques to reveal the neuroanatomical distribution of type 1 cannabinoid receptor (CB1) in the brain, at the cellular and subcellular level, are mainly represented by light, confocal, and electron microscopy. By using immunoperoxidase and immunofluorescence methods, it is possible to reveal CB1 distribution and localization in the brain and its changes under pathological conditions. Moreover, by using electron microscopy, we can define the ultrastructural localization at the level of subcellular structures and organelles. Here, we describe immunoperoxidase, immunofluorescence, and electron microscopy protocols used to get information about CB1 spatial distribution and localization in the brain. Preparation of reagents, resin embedding, preparation for an endogenous activity-blocking step, and background counterstaining and revelation of CB1 by using specific labeled secondary antibodies will be presented. The methods here discussed are highly sensitive and specific multistep processes, where each step is critical to finally obtain an optimum signal.


Assuntos
Encéfalo , Encéfalo/metabolismo , Imunofluorescência , Técnicas Imunoenzimáticas , Microscopia Confocal , Microscopia Eletrônica , Receptores de Canabinoides/metabolismo
15.
Behav Brain Res ; 436: 114060, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-35987307

RESUMO

Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.


Assuntos
Depressão , Pupila , Adolescente , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Colina , Colinérgicos , Depressão/diagnóstico por imagem , Ácido Glutâmico , Giro do Cíngulo/diagnóstico por imagem , Humanos , Projetos Piloto , Pupila/fisiologia , Ácido gama-Aminobutírico
16.
Behav Brain Res ; 436: 114085, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36057380

RESUMO

Due to the low cost of production and the strong evolutionary preference for sweet taste in humans, sugar is added to many food products. This leads to often involuntary overconsumption of high amounts of sugar. Yet, growing evidence indicates that high-sugar diets impact brain function and impair cognitive ability. It may be due to physiological changes in specific regions of the brain or/and maladaptive changes in dopamine signalling similar to those observed in the etiology of addiction. In our study, rats from the experimental group were kept on a feeding protocol involving intermittent access to sucrose solution for eight weeks. Then, the animals underwent a spontaneous exploration test in an experimental arena divided into three zones where stationary and movable objects were placed. Studying the rats' exploratory behaviour allowed us to assess the impact of the sucrose diet on a broad spectrum of behaviours related to the general functioning of the organism in its environment. Analyses showed differences in reaction to novelty between different diet groups which had been placed in different experimental setups. Rats from the sugar-fed group responded to change with more pronounced exploratory behaviours directed at the source of the novel stimuli and the surrounding environment. These results may indicate a lower reward value of novelty resulting from diminished responsiveness of the reward system in the sugar-diet group. We have not found evidence for memory and/or learning impairments in rats on the sugar-rich diet.


Assuntos
Comportamento Exploratório , Sacarose , Animais , Encéfalo , Dopamina , Humanos , Ratos , Recompensa
17.
Behav Brain Res ; 436: 114102, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36089101

RESUMO

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that presents sex differences in the severity and presentation of symptoms, whose neurobiological basis is still unknown. Both Growth-associated Protein 43 (GAP-43) and Sonic hedgehog (Shh) are considered essential proteins for the appropriate brain development, but their participation in ADHD neurobiology have not been investigated yet. In this study, we hypothesized that alterations in these proteins could be related to behavioral traits to ADHD phenotype. Thus, both sexes of infant Spontaneously hypertensive rats (SHR, used as ADHD animal model) were evaluated for developmental milestones, locomotor activity, olfactory and recognition memory. Both GAP-43 and Shh were assessed in the olfactory bulb, frontal cortex and hippocampus in early and late infancy. During early infancy, SHR reached three developmental milestones later, and females showed olfactory memory impairment accompanied by increased levels of Shh in the olfactory bulb. In later infancy, hyperlocomotion, impaired recognition memory, and decreased Shh in the hippocampus were observed in SHR from both sexes. While in early infancy GAP-43 was not altered, it was decreased in the frontal cortex and hippocampus of female SHR in late infancy. Therefore, both Shh and GAP-43 are involved in the sex-dependent behavioral alterations showed by infant SHR. Despite the disorder's complexity and heterogeneity, our findings reveal important developmental parameters during SHR development and also emphasizes the relevance of studying sex differences in the ADHD context.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Proteínas Hedgehog , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Proteína GAP-43/metabolismo , Proteínas Hedgehog/metabolismo , Masculino , Transtornos da Memória/metabolismo , Odorantes , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Caracteres Sexuais
18.
Behav Brain Res ; 436: 114088, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36100008

RESUMO

To understand the processes underpinning social decision-making, we need to determine how internal states respond to information gathered from the social environment. Brain monoamine neurotransmitters are key in the appraisal of the social environment and can reflect the internal state underlying behavioural responses to social stimuli. Here we determined the effects of conspecific partner cooperativeness during predator inspection on brain monoamine metabolic activity in Trinidadian guppies (Poecilia reticulata). We quantified the concentration of dopamine, serotonin and their metabolites across brain sections sampled immediately after ostensibly experiencing cooperation or defection from social partners whilst inspecting a predator model, using a familiar object as a control condition. Our results indicate dopaminergic and serotonergic activity differs with the cooperativeness experienced; these different neurotransmission profiles are likely to affect the expression and regulation of downstream behaviours that ultimately contribute to the patterning of cooperative interactions among individuals in a population.


Assuntos
Poecilia , Animais , Encéfalo , Comportamento Cooperativo , Dopamina , Feminino , Humanos , Poecilia/fisiologia , Serotonina
19.
Adv Neurobiol ; 29: 255-280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255678

RESUMO

O-GlcNAc is the attachment of ß-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. It is generally not further elongated but exists as a monosaccharide that can be rapidly added or removed. Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer's disease. In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system.


Assuntos
Acetilglucosamina , Encéfalo , Acetilglucosamina/metabolismo , Encéfalo/metabolismo , Fenótipo , Serina , Monossacarídeos , Treonina
20.
Methods Mol Biol ; 2571: 133-142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152157

RESUMO

Metabolomics continues to progress, but obstacles remain. The preservation of metabolites in the target tissue and gathering information on the current metabolic state of the organism of interest proves challenging. Robustness, reproducibility, and reliable quantification are necessary for confident metabolite identification and should always be considered for effective biomarker discovery. Recent advancements in analytical platforms, techniques, and data analysis make metabolomics a promising omics for significant research. However, there is no single approach to effectively capturing the metabolome. Coupling separation techniques may improve the power of the analysis and facilitate confident metabolite identification, especially when performing untargeted metabolomics. In this chapter, we will present an untargeted metabolomic analysis of brain tissue from C57BL/6 mice using two UHPLC-MS methods based on reversed-phase and HILIC chromatography.


Assuntos
Metaboloma , Metabolômica , Animais , Biomarcadores , Encéfalo , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes
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