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1.
Mol Cell Endocrinol ; 554: 111711, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35803447

RESUMO

Androgens play an important role in the regulation of hippocampal synaptic plasticity. While the classical molecular mechanism of androgen's genomic activity is their binding to intracellular androgen receptors (iARs), they can also induce rapid non-genomic effects through specific membrane androgen receptors (mARs). In this study, we aimed to localize and characterize these mARs in primary rat hippocampal neurons. Specific punctate fluorescent signals on the cell surface, observed by testosterone-fetal bovine serum albumin conjugated fluorescein isothiocyanate (T-BSA-FITC), indicated the presence of mARs in hippocampal neurons. T-BSA-FITC binding to the cell membrane was incompletely blocked by the iAR-antagonist flutamide, and mAR binding site was competitively bound by free testosterone (T). Most neurons expressing androgen membrane binding sites are glutamatergic (excitatory), although several are γ-aminobutyric acid (GABA)ergic (inhibitory). Confocal microscopy and live-cell imaging techniques were used to observe the real-time rapid effects of androgens on hippocampal dendritic spine morphology. Immunofluorescence cell staining was used to observe their effects on the postsynaptic density protein 95 (PSD95) and synapsin (SYN) synaptic markers. While androgens did not cause a short-term increase in dendritic spine density of rat primary hippocampal neurons, they promoted the transformation of dendritic spines from thin to mushroom, promoted dendritic spine maturation, increased dendritic spine surface area, and rapidly increased PSD95 and SYN expression in the primary hippocampal neurons. Hippocampal synaptosomes were prepared using the Optiprep and Percoll density gradient two-step centrifuge methods, and the gene expression profiles of the synaptosomes and hippocampus were compared using a gene chip; PSD95 mRNA expression was detected by reverse transcription-polymerase chain reaction. Several mRNAs were detected at the synaptic site, including PSD95. Finally, the Venus-PSD95 plasmid was constructed and transfected into HT22 cells, which is a mouse hippocampal neuronal cell line. The real-time effect of androgen on synaptic protein PSD95 was observed by fluorescence recovery after photobleaching experiments, which involved the translation process of PSD95 mRNA. In conclusion, our findings increased our understanding of how androgens exert the neuroprotective mechanisms on synaptic plasticity.


Assuntos
Androgênios , Receptores Androgênicos , Androgênios/metabolismo , Androgênios/farmacologia , Animais , Espinhas Dendríticas/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/farmacologia , Hipocampo/metabolismo , Camundongos , Plasticidade Neuronal , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Ratos , Receptores Androgênicos/metabolismo , Testosterona/farmacologia
2.
Mol Cell Neurosci ; 121: 103755, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35850447

RESUMO

Dendritic spines are small, ratchet-like protrusions on neuronal dendrites that form synapses for receiving neuronal messages. Dendritic spine morphology is associated with synapse function. If neurons degrade or are damaged, the spine morphology of neurons changes. Given that most commercially available spine analysis software is expensive and complex, this study investigated a semi-automated spine analysis software, CTSpine, and used previously published data to verify the accuracy of the analysis results of this software. We also applied CTSpine to understand whether aging causes alterations in the hippocampal spine morphology and whether physical exercise can impede dendritic spine changes in 20 male Sprague Dawley rats. The spines of pyramidal cells in the hippocampal Cornu Ammonis 1 (CA1) region in the aging group were more enriched in filopodium type pattern than those in the control group, whereas the spines of the exercised aging group showed a similar pattern to that of the control. No significant changes were observed in neuronal dendritic spines in other hippocampal regions. However, long-term hippocampal memory was considerably decreased in the aging group, which was reversed to some extent in the exercised aging group. CTSpine, a self-developed semi-automatic spine analysis software, showed results similar to those noted in published data and can be effectively applied to the study of dendritic patterns, including neurodevelopment and disease.


Assuntos
Espinhas Dendríticas , Natação , Envelhecimento , Animais , Espinhas Dendríticas/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley , Software
3.
J Gen Physiol ; 154(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35819365

RESUMO

Dendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling step during postsynaptic activation and is a determinant of synaptic weight change. Dendritic spines also come in a variety of sizes and shapes. To probe the relationship between calcium dynamics and spine morphology, we used a stochastic reaction-diffusion model of calcium dynamics in idealized and realistic geometries. We show that despite the stochastic nature of the various calcium channels, receptors, and pumps, spine size and shape can modulate calcium dynamics and subsequently synaptic weight updates in a deterministic manner. Through a series of exhaustive simulations and analyses, we found that the calcium dynamics and synaptic weight change depend on the volume-to-surface area of the spine. The relationships between calcium dynamics and spine morphology identified in idealized geometries also hold in realistic geometries, suggesting that there are geometrically determined deterministic relationships that may modulate synaptic weight change.


Assuntos
Cálcio , Espinhas Dendríticas , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Espinhas Dendríticas/metabolismo , Difusão
4.
Sci Rep ; 12(1): 12405, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35859092

RESUMO

Live fluorescence imaging has demonstrated the dynamic nature of dendritic spines, with changes in shape occurring both during development and in response to activity. The structure of a dendritic spine correlates with its functional efficacy. Learning and memory studies have shown that a great deal of the information stored by a neuron is contained in the synapses. High precision tracking of synaptic structures can give hints about the dynamic nature of memory and help us understand how memories evolve both in biological and artificial neural networks. Experiments that aim to investigate the dynamics behind the structural changes of dendritic spines require the collection and analysis of large time-series datasets. In this paper, we present an open-source software called SpineS for automatic longitudinal structural analysis of dendritic spines with additional features for manual intervention to ensure optimal analysis. We have tested the algorithm on in-vitro, in-vivo, and simulated datasets to demonstrate its performance in a wide range of possible experimental scenarios.


Assuntos
Espinhas Dendríticas , Software , Algoritmos , Espinhas Dendríticas/fisiologia , Sinapses/fisiologia , Fatores de Tempo
5.
Dis Model Mech ; 15(7)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35781563

RESUMO

Bisphenol-A (BPA) is a representative endocrine disruptor, widely used in a variety of products including plastics, medical equipment and receipts. Hence, most people are exposed to BPA via the skin, digestive system or inhalation in everyday life. Furthermore, BPA crosses the blood-brain barrier and is linked to multiple neurological dysfunctions found in neurodegenerative and neuropsychological disorders. However, the mechanisms underlying BPA-associated neurological dysfunctions remain poorly understood. Here, we report that BPA exposure alters synapse morphology and function in the cerebral cortex. Cortical pyramidal neurons treated with BPA showed reduced size and number of dendrites and spines. The density of excitatory synapses was also decreased by BPA treatment. More importantly, we found that BPA disrupted normal synaptic transmission and cognitive behavior. RGS4 and its downstream BDNF/NTRK2 pathway appeared to mediate the effect of BPA on synaptic and neurological function. Our findings provide molecular mechanistic insights into anatomical and physiological neurotoxic consequences related to a potent endocrine modifier.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Disruptores Endócrinos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Espinhas Dendríticas/metabolismo , Disruptores Endócrinos/farmacologia , Disruptores Endócrinos/toxicidade , Humanos , Células Piramidais/metabolismo
6.
Neurosci Lett ; 784: 136744, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35718239

RESUMO

Synaptic dysfunction is the prominent feature of many neuropsychiatric and neurological diseases, in which glycogen synthase kinase 3ß (GSK-3ß) has been shown to play a role. Overexpression of constitutively active form of GSK-3ß (GSK-3ß[S9A]) in mice recapitulates the cognitive and structural brain deficits characteristic for manic phase of bipolar disorder (BD). Yet, the mechanisms underlying GSK-3ß-induced synaptic dysfunction have not been fully elucidated. The aim of the present study was to dissect the effect of GSK-3ß overactivity on synaptic function in adolescent (3-week-old) mice. We found that overactivity of GSK-3ß in adolescent transgenic mice leads to an alteration in dendritic spines morphology of granule cells in dentate gyrus (DG) without changes in overall spine density. There was an increase in the number of thin, presumably immature dendritic spines in GSK-3ß[S9A] mice. Subsequent electrophysiological analysis showed changes in excitatory synaptic transmission manifested by an increase of inter-event intervals of miniature excitatory postsynaptic currents (mEPSCs) in DG granule cells and an increase in the number of silent (unfunctional) synapses at the perforant path-DG pathway in GSK-3ß[S9A] mice. Altogether, our data indicate that GSK-3ß overactivity leads to synaptic deficits in adolescent, GSK-3ß[S9A] mice. These data might provide potential mechanisms underlying GSK-3ß-induced synaptic dysfunction in psychiatric disorders.


Assuntos
Espinhas Dendríticas , Glicogênio Sintase Quinase 3 beta , Neurônios , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Sinapses
7.
Int J Mol Sci ; 23(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35743082

RESUMO

Evidence indicates that inhalative anesthetics enhance the ß-site amyloid precursor protein (APP)-cleaving enzyme (BACE) activity, increase amyloid beta 1-42 (Aß1-42) aggregation, and modulate dendritic spine dynamics. However, the mechanisms of inhalative anesthetics on hippocampal dendritic spine plasticity and BACE-dependent APP processing remain unclear. In this study, hippocampal slices were incubated with equipotent isoflurane (iso), sevoflurane (sevo), or xenon (Xe) with/without pretreatment of the BACE inhibitor LY2886721 (LY). Thereafter, CA1 dendritic spine density, APP processing-related molecule expressions, nectin-3 levels, and long-term potentiation (LTP) were tested. The nectin-3 downregulation on LTP and dendritic spines were evaluated. Sevo treatment increased hippocampal mouse Aß1-42 (mAß1-42), abolished CA1-LTP, and decreased spine density and nectin-3 expressions in the CA1 region. Furthermore, CA1-nectin-3 knockdown blocked LTP and reduced spine density. Iso treatment decreased spine density and attenuated LTP. Although Xe blocked LTP, it did not affect spine density, mAß1-42, or nectin-3. Finally, antagonizing BACE activity partly restored sevo-induced deficits. Taken together, our study suggests that sevo partly elevates BACE activity and interferes with synaptic remodeling, whereas iso mildly modulates synaptic changes in the CA1 region of the hippocampus. On the other hand, Xe does not alternate dendritic spine remodeling.


Assuntos
Precursor de Proteína beta-Amiloide , Anestésicos , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Anestésicos/farmacologia , Animais , Espinhas Dendríticas/metabolismo , Hipocampo/metabolismo , Camundongos , Nectinas/metabolismo , Plasticidade Neuronal , Sevoflurano/farmacologia , Xenônio/metabolismo , Xenônio/farmacologia
8.
Nat Neurosci ; 25(6): 726-737, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35654957

RESUMO

Learning induces the formation of new excitatory synapses in the form of dendritic spines, but their functional properties remain unknown. Here, using longitudinal in vivo two-photon imaging and correlated electron microscopy of dendritic spines in the motor cortex of mice during motor learning, we describe a framework for the formation, survival and resulting function of new, learning-related spines. Specifically, our data indicate that the formation of new spines during learning is guided by the potentiation of functionally clustered preexisting spines exhibiting task-related activity during earlier sessions of learning. We present evidence that this clustered potentiation induces the local outgrowth of multiple filopodia from the nearby dendrite, locally sampling the adjacent neuropil for potential axonal partners, likely via targeting preexisting presynaptic boutons. Successful connections are then selected for survival based on co-activity with nearby task-related spines, ensuring that the new spine preserves functional clustering. The resulting locally coherent activity of new spines signals the learned movement. Furthermore, we found that a majority of new spines synapse with axons previously unrepresented in these dendritic domains. Thus, learning involves the binding of new information streams into functional synaptic clusters to subserve learned behaviors.


Assuntos
Aprendizagem , Sinapses , Animais , Axônios , Espinhas Dendríticas , Camundongos , Neurópilo , Terminações Pré-Sinápticas , Sinapses/metabolismo
10.
J Vis Exp ; (179)2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35687674

RESUMO

ARTICLES DISCUSSED: Pekarek, B. T., Hunt, P. J., Belfort, B. D. W., Liu, G., Arenkiel, B. R. Imaging and quantification of intact neuronal dendrites via CLARITY tissue clearing. Journal of Visualized Experiments: JoVE. (170), e62532 (2021). Frankfurt, M., Bowman, R. Rapid Golgi stain for dendritic spine visualization in hippocampus and prefrontal cortex. Journal of Visualized Experiments: JoVE. (178), e63404 (2021). Sliwinska, M. A., Caly, A., Szymanski, J., Radwanska, K. Serial Block-Face Scanning Electron Microscopy (SBEM) for the study of dendritic spines. Journal of Visualized Experiments: JoVE. (176), e62712 (2021). Chan, U., Gautam, D., West, A. E. Utilizing in vivo postnatal electroporation to study cerebellar granule neuron morphology and synapse development. Journal of Visualized Experiments: JoVE. (172), e62568 (2021). Cuentas-Condori, A., Miller III, D. M. Imaging dendritic spines in Caenorhabditis elegans. Journal of Visualized Experiments: JoVE. (175), e62676 (2021).


Assuntos
Dendritos , Sinapses , Dendritos/fisiologia , Espinhas Dendríticas , Complexo de Golgi , Hipocampo/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
11.
eNeuro ; 9(3)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35610025

RESUMO

Dendritic spines have diverse morphologies, with a wide range of head and neck sizes, and these morphologic differences likely generate different functional properties. To explore how this morphologic diversity differs across species and ages we analyzed 3D confocal reconstructions of ∼8000 human spines and ∼1700 mouse spines, labeled by intracellular injections in fixed tissue. Using unsupervised algorithms, we computationally separated spine heads and necks and systematically measured morphologic features of spines in apical and basal dendrites from cortical pyramidal cells. Human spines had unimodal distributions of parameters, without any evidence of morphologic subtypes. Their spine necks were longer and thinner in apical than in basal spines, and spine head volumes of an 85-year-old individual were larger than those of a 40-year-old individual. Human spines had longer and thicker necks and larger head volumes than mouse spines. Our results indicate that human spines form part of a continuum, are larger and longer than those of mice, and become larger with increasing adult age. These morphologic differences in spines across species could generate functional differences in biochemical and electrical spine compartmentalization, or in synaptic properties, across species and ages.


Assuntos
Espinhas Dendríticas , Células Piramidais , Animais , Dendritos , Humanos , Camundongos
12.
J Neurochem ; 162(2): 166-189, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35621027

RESUMO

The nucleus accumbens (NAc) is the key area of the reward circuit, but its heterogeneity has been poorly studied. Using single-cell RNA sequencing, we revealed a subcluster of GABAergic neurons characterized by cell division cycle 20 (Cdc20) mRNA expression in the NAc of adult rats. We studied the coexpression of Cdc20 and Gad1 mRNA in the NAc neurons of adult rats and assessed Cdc20 protein expression in the NAc during rat development. Moreover, we microinjected AAV2/9-hSyn-Cdc20 with or without the dual-AAV system into the bilateral NAc for sparse labeling to observe changes in the synaptic morphology of mature neurons and assessed rat behaviors in open field and elevated plus maze tests. Furthermore, we performed the experiments with a Cdc20 inhibitor, Cdc20 over-expression AAV vector, and Cdc20 conditional knockout primary striatal neurons to understand the ubiquitination-dependent degradation of fragile X mental retardation protein (FMRP) in vitro and in vivo. We confirmed the mRNA expression of Cdc20 in the NAc GABAergic neurons of adult rats, and its protein level was decreased significantly 3 weeks post-birth. Up-regulated Cdc20 expression in the bilateral NAc decreased the dendritic spine density in mature neurons and induced anxiety-like behavior in rats. Cdc20-APC triggered FMRP degradation through K48-linked polyubiquitination in Neuro-2a cells and primary striatal neurons and down-regulated FMRP expression in the NAc of adult rats. These data revealed that up-regulation of Cdc20 in the bilateral NAc reduced dendritic spine density and led to anxiety-like behaviors, possibly by enhancing FMRP degradation via K48-linked polyubiquitination.


Assuntos
Proteínas Cdc20 , Espinhas Dendríticas , Proteína do X Frágil de Retardo Mental , Animais , Proteínas Cdc20/genética , Ciclo Celular , Espinhas Dendríticas/metabolismo , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ubiquitinação , Regulação para Cima
13.
Phys Biol ; 19(4)2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35508164

RESUMO

Effective treatments that prevent or reduce drug relapse vulnerability should be developed to relieve the high burden of drug addiction on society. This will only be possible by enhancing the understanding of the molecular mechanisms underlying the neurobiology of addiction. Recent experimental data have shown that dendritic spines, small protrusions from the dendrites that receive excitatory input, of spiny neurons in the nucleus accumbens exhibit morphological changes during drug exposure and withdrawal. Moreover, these changes relate to the characteristic drug-seeking behavior of addiction. However, due to the complexity of dendritic spines, we do not yet fully understand the processes underlying their structural changes in response to different inputs. We propose that biophysical models can enhance the current understanding of these processes by incorporating different, and sometimes, discrepant experimental data to identify the shared underlying mechanisms and generate experimentally testable hypotheses. This review aims to give an up-to-date report on biophysical models of dendritic spines, focusing on those models that describe their shape changes, which are well-known to relate to learning and memory. Moreover, it examines how these models can enhance our understanding of the effect of the drugs and the synaptic changes during withdrawal, as well as during neurodegenerative disease progression such as Alzheimer's disease.


Assuntos
Espinhas Dendríticas , Doenças Neurodegenerativas , Espinhas Dendríticas/fisiologia , Humanos , Plasticidade Neuronal , Neurônios/fisiologia
14.
Dev Biol ; 488: 68-73, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35580729

RESUMO

The morphogenesis and plasticity of dendritic spines are associated with synaptic strength, learning, and memory. Dendritic spines are highly compartmentalized structures, which makes proteins involved in cellular polarization and membrane compartmentalization likely candidates regulating their formation and maintenance. Indeed, recent studies suggest polarity proteins help form and maintain dendritic spines by compartmentalizing the spine neck and head. Here, we review emerging evidence that polarity proteins regulate dendritic spine plasticity and stability through the cytoskeleton, scaffolding molecules, and signaling molecules. We specifically analyze various polarity complexes known to contribute to different forms of cell polarization processes and examine the essential conceptual context linking these groups of polarity proteins to dendritic spine morphogenesis, plasticity, and cognitive functions.


Assuntos
Espinhas Dendríticas , Plasticidade Neuronal , Citoesqueleto , Espinhas Dendríticas/metabolismo , Morfogênese , Plasticidade Neuronal/fisiologia , Transdução de Sinais , Sinapses/metabolismo
15.
Neurobiol Dis ; 170: 105772, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35605760

RESUMO

Schizophrenia is a psychiatric disorder that affects over 20 million people globally. Notably, schizophrenia is associated with decreased density of dendritic spines and decreased levels of d-serine, a co-agonist required for opening of the N-methyl-d-aspartate receptor (NMDAR). We hypothesized that lowered d-serine levels associated with schizophrenia would enhance ion flux-independent signaling by the NMDAR, driving destabilization and loss of dendritic spines. We tested our hypothesis using the serine racemase knockout (SRKO) mouse model, which lacks the enzyme for d-serine production. We show that activity-dependent spine growth is impaired in SRKO mice, but can be acutely rescued by exogenous d-serine. Moreover, we find a significant bias of synaptic plasticity toward spine shrinkage in the SRKO mice as compared to wild-type littermates. Notably, we demonstrate that enhanced ion flux-independent signaling through the NMDAR contributes to this bias toward spine destabilization, which is exacerbated by an increase in synaptic NMDARs in hippocampal synapses of SRKO mice. Our results support a model in which lowered d-serine levels associated with schizophrenia enhance ion flux-independent NMDAR signaling and bias toward spine shrinkage and destabilization.


Assuntos
Receptores de N-Metil-D-Aspartato , Esquizofrenia , Animais , Espinhas Dendríticas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Plasticidade Neuronal , Serina
16.
Cell Mol Life Sci ; 79(5): 278, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35505150

RESUMO

Alterations in social behavior are core symptoms of major developmental neuropsychiatric diseases such as autism spectrum disorders or schizophrenia. Hence, understanding their molecular and cellular underpinnings constitutes the major research task. Dysregulation of the global gene expression program in the developing brain leads to modifications in a number of neuronal connections, synaptic strength and shape, causing unbalanced neuronal plasticity, which may be important substrate in the pathogenesis of neurodevelopmental disorders, contributing to their clinical outcome. Serum response factor (SRF) is a major transcription factor in the brain. The behavioral influence of SRF deletion during neuronal differentiation and maturation has never been studied because previous attempts to knock-out the gene caused premature death. Herein, we generated mice that lacked SRF from early postnatal development to precisely investigate the role of SRF starting in the specific time window before maturation of excitatory synapses that are located on dendritic spine occurs. We show that the time-controlled loss of SRF in neurons alters specific aspects of social behaviors in SRF knock-out mice, and causes deficits in developmental spine maturation at both the structural and functional levels, including downregulated expression of the AMPARs subunits GluA1 and GluA2, and increases the percentage of filopodial/immature dendritic spines. In aggregate, our study uncovers the consequences of postnatal SRF elimination for spine maturation and social interactions revealing novel mechanisms underlying developmental neuropsychiatric diseases.


Assuntos
Fator de Resposta Sérica/metabolismo , Interação Social , Animais , Espinhas Dendríticas/fisiologia , Camundongos , Plasticidade Neuronal , Fator de Resposta Sérica/genética , Sinapses/metabolismo
17.
Cells ; 11(10)2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35626653

RESUMO

The interaction of Rabphilin-3A (Rph3A) with the NMDA receptor (NMDAR) in hippocampal neurons plays a pivotal role in the synaptic retention of this receptor. The formation of a Rph3A/NMDAR complex is needed for the induction of long-term potentiation and NMDAR-dependent hippocampal behaviors, such as spatial learning. Moreover, Rph3A can also interact with AMPA receptors (AMPARs) through the formation of a complex with myosin Va. Here, we used a confocal imaging approach to show that Rph3A overexpression in primary hippocampal neuronal cultures is sufficient to promote increased dendritic spine density. This morphological event is correlated with an increase in GluN2A-containing NMDARs at synaptic membranes and a decrease in the surface levels of GluA1-containing AMPARs. These molecular and morphological modifications of dendritic spines are sufficient to occlude the spine formation induced by long-term potentiation, but do not prevent the spine loss induced by long-term depression. Overall, our results demonstrate a key role for Rph3A in the modulation of structural synaptic plasticity at hippocampal synapses that correlates with its interactions with both NMDARs and AMPARs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Espinhas Dendríticas , Proteínas do Tecido Nervoso , Proteínas de Transporte Vesicular , Animais , Espinhas Dendríticas/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Ratos , Receptores de AMPA , Proteínas de Transporte Vesicular/metabolismo
18.
Neurosci Lett ; 782: 136688, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35595189

RESUMO

Nearly one-third of persons infected with HIV-1 (PWH) develop HIV-associated neurocognitive disorders (HAND), which can be exacerbated by exposure to opioids. The impact of opioids on HIV-induced alterations in neuronal plasticity is less well understood. Both morphine exposure and HIV have been shown to disrupt synaptic growth and stability in the hippocampus suggesting a potential site of convergence for their deleterious effects. In the present study, we examined the density of dendritic spines in CA1 and CA3 pyramidal neurons, and granule neurons within the dentate gyrus representing the hippocampal trisynaptic pathway after short-term exposure to the HIV transactivator of transcription (Tat) protein and morphine. We exposed inducible male, HIV-1 Tat transgenic mice to escalating doses of morphine (10-40 mg/kg, b.i.d.) and examined synaptodendritic structure in Golgi-impregnated hippocampal neurons. HIV-1 Tat, but not morphine, systematically reduced the density of apical, but not basilar, dendrites of CA1 and CA3 pyramidal neurons, and granule neuronal apical dendrites, suggesting the coordinated loss of specific synaptic interconnections throughout the hippocampal trisynaptic pathway.


Assuntos
Espinhas Dendríticas , HIV-1 , Analgésicos Opioides/farmacologia , Animais , Dendritos/metabolismo , Hipocampo , Masculino , Camundongos , Camundongos Transgênicos , Morfina/metabolismo , Morfina/farmacologia
19.
Curr Opin Neurobiol ; 74: 102534, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35398661

RESUMO

Induction of long-term synaptic potentiation (LTP) in excitatory neurons triggers a transient enlargement of dendritic spines followed by decay to sustained size expansion, a process termed structural LTP which contributes to the cellular basis of learning and memory. The activity-induced structural changes in dendritic spines involve spatiotemporal coordination of actin cytoskeleton reorganization, membrane trafficking and membrane remodeling. In this review, we discuss recent progresses in understanding the complex mechanisms underlying structural LTP, with an emphasis on the interplay between the spine plasma membrane and the actin cytoskeleton. We also highlight open questions and challenges to further understand this interesting cell neurobiological phenomenon.


Assuntos
Espinhas Dendríticas , Plasticidade Neuronal , Citoesqueleto de Actina/metabolismo , Espinhas Dendríticas/fisiologia , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Transdução de Sinais , Sinapses/fisiologia
20.
Neural Plast ; 2022: 7251460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465396

RESUMO

Objective: The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods: In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results: Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats (p < 0.001). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) (p < 0.001). Conclusions: Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat's brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.


Assuntos
Espinhas Dendríticas , Córtex Somatossensorial , Animais , Modelos Animais de Doenças , Eletroencefalografia , Privação Materna , Células Piramidais , Ratos , Ratos Wistar
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