MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning

Minkeviciene, Rimante; Hlushchenko, Iryna; Virenque, Anaïs; Lahti, Lauri; Khanal, Pushpa; Rauramaa, Tuomas; Koistinen, Arto; Leinonen, Ville; Noè, Francesco M.; Hotulainen, Pirta

doi:10.3389/fnmol.2019.00276

Cited by 16 publications

(20 citation statements)

References 36 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent papers identified MIM as an important regulator of DF in Purkinje cells of the cerebellum and cortical neurons (Galbraith et al, 2018;Saarikangas et al, 2015). Although knockdown of MIM in EVL KO neurons strikingly reduced protrusion density in our study, it did not eliminate DF in WT neurons; this is in agreement with observations in MIM KO mouse strains (Galbraith et al, 2018;Minkeviciene et al, 2019;Saarikangas et al, 2015), suggesting possible functional redundancy with other I-BAR proteins. Indeed, IRSp53 is also implicated in dendritic spine formation, synaptic plasticity, and neurodevelopmental disorders (Choi et al, 2005;Chung et al, 2015;Kang et al, 2016).…”

Section: Mim Plays a Critical Role In Supporting Evl Function In Dfsupporting

confidence: 91%

EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons

Grant

et al. 2021

Preprint

View full text Add to dashboard Cite

Dendritic spines are the postsynaptic compartment of a functional neuronal synapse, and are critical for synaptic connectivity and plasticity. The developmental precursor to dendritic spines, dendritic filopodia, are highly motile protrusions that facilitate synapse formation by sampling the environment for suitable axon partners during development and learning. Despite the significance of the actin cytoskeleton in driving these protrusions, the actin remodeling factors involved in this process are not fully characterized. In this work, we identify a critical function for the Ena/VASP protein EVL in the regulation of dendritic filopodia. Amongst the Ena/VASP proteins, EVL is uniquely required for the characteristic morphology and dynamics of dendritic filopodia. Using a combination of genetic and optogenetic manipulations, we demonstrate that EVL promotes protrusive motility through membrane-direct actin polymerization at dendritic filopodia tips. EVL forms a complex at nascent protrusions and dendritic filopodia tips with MIM/MTSS1, an I-BAR protein recently discovered to be important for initiation of dendritic filopodia. We propose a model in which EVL cooperates with MIM to elongate and coalesce branched actin filaments, establishing the dynamic lamellipodia-like architecture of dendritic filopodia in developing neurons.

show abstract

Section: Mim Plays a Critical Role In Supporting Evl Function In Dfsupporting

confidence: 91%

EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons

Grant

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Similar to the iF-BAR domain of SrGAP3, I-BAR bends the membrane outwards resulting in a protrusion from the flat membrane. MIM/Mtss1 is broadly expressed in the mouse brain during early development, but in the adult brain the expression of MIM/Mtss1 is limited to the cerebellum [ 112 ]. Thus, it is expected that MIM/Mtss1 is important for brain development, but later in life, it mainly regulates spine density in the Purkinje neurons of the cerebellum, in which MIM/Mtss1 exhibits the highest expression.…”

Section: Known Mechanisms Of Spine Initiationmentioning

confidence: 99%

“…MIM/MTSS1 overexpression led to increased spine density in vitro and MIM/MTSS1 knockout led to reduced spine density in vitro and in vivo in early development [ 111 ]. The loss of MIM/MTSS1 resulted in defects in motor coordination and reverse learning [ 111 , 112 ]. These defects can be due to alteration in spine initiation, but results are complicated by the fact that loss of MIM/MTSS1, similar to SrGAP3 [ 91 ], leads to enlarged ventricles [ 112 ].…”

Section: Known Mechanisms Of Spine Initiationmentioning

confidence: 99%

“…The loss of MIM/MTSS1 resulted in defects in motor coordination and reverse learning [ 111 , 112 ]. These defects can be due to alteration in spine initiation, but results are complicated by the fact that loss of MIM/MTSS1, similar to SrGAP3 [ 91 ], leads to enlarged ventricles [ 112 ]. Enlarged ventricles cause similar behavioral defects to what are expected to be effects of reduced spine density [ 119 ].…”

Section: Known Mechanisms Of Spine Initiationmentioning

confidence: 99%

See 1 more Smart Citation

Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins

Khanal

Hotulainen

2021

Cells

Self Cite

View full text Add to dashboard Cite

Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain increases rapidly before and after birth achieving the highest density around 2–8 years. Density decreases during adolescence, reaching a stable level in adulthood. The changes in dendritic spines are considered structural correlates for synaptic plasticity as well as the basis of experience-dependent remodeling of neuronal circuits. Alterations in spine density correspond to aberrant brain function observed in various neurodevelopmental and neuropsychiatric disorders. Dendritic spine initiation affects spine density. In this review, we discuss the importance of spine initiation in brain development, learning, and potential complications resulting from altered spine initiation in neurological diseases. Current literature shows that two Bin Amphiphysin Rvs (BAR) domain-containing proteins, MIM/Mtss1 and SrGAP3, are involved in spine initiation. We review existing literature and open databases to discuss whether other BAR-domain proteins could also take part in spine initiation. Finally, we discuss the potential molecular mechanisms on how BAR-domain proteins could regulate spine initiation.

show abstract

“…The maximum force was recorded in gram-force (gf). Three tests were performed on each mouse, and the average score was used for statistical analysis [11].…”

Section: Grip-strength Measurementmentioning

confidence: 99%

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Xiao

Xie

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Anxiety disorder, the most common mental health issue, can cause palpitations, fear, and compulsive behavior, and can severely endanger human health. Most drugs to treat anxiety disorder can cause a variety of side effects, therefore, it is important to seek natural and safe complementary and alternative therapies.Methods: The open field (OF), elevated plus maze (EPM), and light-dark box (LDB) tests were used to confirm the anxiolytic effect of BEO in mice. Further, we constructed a component-target-signaling pathway network and a protein-protein interaction (PPI) network for the regulation of anxiety by BEO through pharmacological network analyses, and performed Gene Ontology (GO) enrichment analyses of BEO targets, and analyzed the active components and targets of BEO through molecular docking.Results: In the OF test, BEO significantly prolonged the time spent by the mice in the central area (p < 0.05), in a dose dependent manner (r = 0.9992), and also significantly increased the number of central area entries (p < 0.01). In the EPM test, BEO significantly increased the time spent in the open arms (p < 0.01) and the number of entries into the open arms (p < 0.01) in a dose-dependent manner (r = 0.9733, r = 0.9669). In the LDB tests, BEO significantly increased the light area duration (p < 0.05) and the transition number (p < 0.01) in a dose-dependent manner (r = 0.9166, r = 0.9572), thus confirming its anxiolytic effect. Network pharmacology results showed that 33 active components in BEO acted on 54 targets, mainly through modulation of neuroactive ligand-receptor interactions, G-protein coupled receptor signaling pathways, and RNA polymerase II transcription factor activity. PPI network analysis identified 48 key proteins, including estrogen receptor 1 (ESR1), androgen receptor (AR), and mitogen-activated protein kinase 8 (MAPK8). Molecular docking results showed that the main active components of BEO are borneol, β-caryophyllene, α-cadinol, limonene, and α- selinene, which act on the key targets CNR2, ADRA2B, and ADORA2A.Conclusion: Our results indicated that BEO has multi-component, multi-target, and multi-pathway characteristics, thus providing a theoretical basis for further research on the mechanism of action of BEO as a potential anxiolytic agent.

show abstract

MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning

Cited by 16 publications

References 36 publications

EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons

EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons

Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Contact Info

Product

Resources

About