LIVIVO - Search results -

Search results

Result 1 - 10 of total 65

Search options

Article ; Online: The intracellular domain of major histocompatibility class-I proteins is essential for maintaining excitatory spine density and synaptic ultrastructure in the brain.

Lazarczyk, Maciej J / Eyford, Brett A / Varghese, Merina / Arora, Hitesh / Munro, Lonna / Warda, Tahia / Pfeifer, Cheryl G / Sowa, Allison / Dickstein, Daniel R / Rumbell, Timothy / Jefferies, Wilfred A / Dickstein, Dara L

Scientific reports

2023 Volume 13, Issue 1, Page(s) 6448

Abstract: Major histocompatibility complex class I (MHC-I) proteins are expressed in neurons, where they regulate synaptic plasticity. However, the mechanisms by which MHC-I functions in the CNS remains unknown. Here we describe the first structural analysis of a ... ...

Abstract	Major histocompatibility complex class I (MHC-I) proteins are expressed in neurons, where they regulate synaptic plasticity. However, the mechanisms by which MHC-I functions in the CNS remains unknown. Here we describe the first structural analysis of a MHC-I protein, to resolve underlying mechanisms that explains its function in the brain. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine-based endocytosis motif YXXΦ in MHC-I affects spine density and synaptic structure without affecting neuronal complexity in the hippocampus, a region of the brain intimately involved in learning and memory. Furthermore, the impact of the Y321F substitution phenocopies MHC-I knock-out (null) animals, demonstrating that reverse, outside-in signalling events sensing the external environment is the major mechanism that conveys this information to the neuron and this has a previously undescribed yet essential role in the regulation of synaptic plasticity.
MeSH term(s)	Animals ; Brain/metabolism ; Neurons/metabolism ; Neuronal Plasticity/physiology ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Signal Transduction ; Hippocampus/metabolism
Chemical Substances	Histocompatibility Antigens Class I
Language	English
Publishing date	2023-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30054-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.

Eyford, Brett A / Lazarczyk, Maciej J / Choi, Kyung Bok / Varghese, Merina / Arora, Hitesh / Kari, Suresh / Munro, Lonna / Pfeifer, Cheryl G / Sowa, Allison / Dickstein, Daniel R / Dickstein, Dara L / Jefferies, Wilfred A

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13079

Abstract: The interplay between AMPA-type glutamate receptors (AMPARs) and major histocompatibility complex class I (MHC-I) proteins in regulating synaptic signaling is a crucial aspect of central nervous system (CNS) function. In this study, we investigate the ... ...

Abstract	The interplay between AMPA-type glutamate receptors (AMPARs) and major histocompatibility complex class I (MHC-I) proteins in regulating synaptic signaling is a crucial aspect of central nervous system (CNS) function. In this study, we investigate the significance of the cytoplasmic tail of MHC-I in synaptic signaling within the CNS and its impact on the modulation of synaptic glutamate receptor expression. Specifically, we focus on the Y321 to F substitution (Y321F) within the conserved cytoplasmic tyrosine YXXΦ motif, known for its dual role in endocytosis and cellular signaling of MHC-I. Our findings reveal that the Y321F substitution influences the expression of AMPAR subunits GluA2/3 and leads to alterations in the phosphorylation of key kinases, including Fyn, Lyn, p38, ERK1/2, JNK1/2/3, and p70 S6 kinase. These data illuminate the crucial role of MHC-I in AMPAR function and present a novel mechanism by which MHC-I integrates extracellular cues to modulate synaptic plasticity in neurons, which ultimately underpins learning and memory.
MeSH term(s)	Glutamic Acid/metabolism ; Signal Transduction ; Receptors, Glutamate/genetics ; Receptors, Glutamate/metabolism ; Neurons/metabolism ; Receptors, AMPA/metabolism ; Major Histocompatibility Complex
Chemical Substances	Glutamic Acid (3KX376GY7L) ; Receptors, Glutamate ; Receptors, AMPA
Language	English
Publishing date	2023-08-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38663-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Galactic cosmic radiation exposure causes multifaceted neurocognitive impairments.

Alaghband, Yasaman / Klein, Peter M / Kramár, Eniko A / Cranston, Michael N / Perry, Bayley C / Shelerud, Lukas M / Kane, Alice E / Doan, Ngoc-Lien / Ru, Ning / Acharya, Munjal M / Wood, Marcelo A / Sinclair, David A / Dickstein, Dara L / Soltesz, Ivan / Limoli, Charles L / Baulch, Janet E

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 1, Page(s) 29

Abstract: Technological advancements have facilitated the implementation of realistic, terrestrial-based complex 33-beam galactic cosmic radiation simulations (GCR Sim) to now probe central nervous system functionality. This work expands considerably on prior, ... ...

Abstract	Technological advancements have facilitated the implementation of realistic, terrestrial-based complex 33-beam galactic cosmic radiation simulations (GCR Sim) to now probe central nervous system functionality. This work expands considerably on prior, simplified GCR simulations, yielding new insights into responses of male and female mice exposed to 40-50 cGy acute or chronic radiations relevant to deep space travel. Results of the object in updated location task suggested that exposure to acute or chronic GCR Sim induced persistent impairments in hippocampus-dependent memory formation and reconsolidation in female mice that did not manifest robustly in irradiated male mice. Interestingly, irradiated male mice, but not females, were impaired in novel object recognition and chronically irradiated males exhibited increased aggressive behavior on the tube dominance test. Electrophysiology studies used to evaluate synaptic plasticity in the hippocampal CA1 region revealed significant reductions in long-term potentiation after each irradiation paradigm in both sexes. Interestingly, network-level disruptions did not translate to altered intrinsic electrophysiological properties of CA1 pyramidal cells, whereas acute exposures caused modest drops in excitatory synaptic signaling in males. Ultrastructural analyses of CA1 synapses found smaller postsynaptic densities in larger spines of chronically exposed mice compared to controls and acutely exposed mice. Myelination was also affected by GCR Sim with acutely exposed mice exhibiting an increase in the percent of myelinated axons; however, the myelin sheathes on small calibur (< 0.3 mm) and larger (> 0.5 mm) axons were thinner when compared to controls. Present findings might have been predicted based on previous studies using single and mixed beam exposures and provide further evidence that space-relevant radiation exposures disrupt critical cognitive processes and underlying neuronal network-level plasticity, albeit not to the extent that might have been previously predicted.
MeSH term(s)	Female ; Mice ; Male ; Animals ; Hippocampus ; Synapses ; Long-Term Potentiation ; Neuronal Plasticity ; Radiation Exposure
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04666-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 195: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats.

Krishnan, Balaji / Natarajan, Chandramouli / Bourne, Krystyn Z / Alikhani, Leila / Wang, Juan / Sowa, Allison / Groen, Katherine / Perry, Bayley / Dickstein, Dara L / Baulch, Janet E / Limoli, Charles L / Britten, Richard A

International journal of molecular sciences

2021 Volume 22, Issue 7

Abstract: The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/ ... ...

Abstract	The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.
MeSH term(s)	Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; CA1 Region, Hippocampal/metabolism ; CA1 Region, Hippocampal/radiation effects ; Cosmic Radiation/adverse effects ; Dendrites/radiation effects ; Disks Large Homolog 4 Protein/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/radiation effects ; Neutrons/adverse effects ; Prefrontal Cortex/radiation effects ; Rats ; Rats, Wistar
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD68 protein, mouse ; Disks Large Homolog 4 Protein ; Dlg4 protein, mouse
Language	English
Publishing date	2021-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22073668
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats

Balaji Krishnan / Chandramouli Natarajan / Krystyn Z. Bourne / Leila Alikhani / Juan Wang / Allison Sowa / Katherine Groen / Bayley Perry / Dara L. Dickstein / Janet E. Baulch / Charles L. Limoli / Richard A. Britten

International Journal of Molecular Sciences, Vol 22, Iss 3668, p

2021 Volume 3668

Abstract	The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.
Keywords	space radiation ; neutrons ; charged particles ; dendritic spines ; myelin ; synapses ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Galactic cosmic radiation exposure causes multifaceted neurocognitive impairments

Alaghband, Yasaman / Klein, Peter M. / Kramár, Eniko A. / Cranston, Michael N. / Perry, Bayley C. / Shelerud, Lukas M. / Kane, Alice E. / Doan, Ngoc-Lien / Ru, Ning / Acharya, Munjal M. / Wood, Marcelo A. / Sinclair, David A. / Dickstein, Dara L. / Soltesz, Ivan / Limoli, Charles L. / Baulch, Janet E.

Cell. Mol. Life Sci.. 2023 Jan., v. 80, no. 1 p.29-29

2023

Abstract	Technological advancements have facilitated the implementation of realistic, terrestrial-based complex 33-beam galactic cosmic radiation simulations (GCR Sim) to now probe central nervous system functionality. This work expands considerably on prior, simplified GCR simulations, yielding new insights into responses of male and female mice exposed to 40-50 cGy acute or chronic radiations relevant to deep space travel. Results of the object in updated location task suggested that exposure to acute or chronic GCR Sim induced persistent impairments in hippocampus-dependent memory formation and reconsolidation in female mice that did not manifest robustly in irradiated male mice. Interestingly, irradiated male mice, but not females, were impaired in novel object recognition and chronically irradiated males exhibited increased aggressive behavior on the tube dominance test. Electrophysiology studies used to evaluate synaptic plasticity in the hippocampal CA1 region revealed significant reductions in long-term potentiation after each irradiation paradigm in both sexes. Interestingly, network-level disruptions did not translate to altered intrinsic electrophysiological properties of CA1 pyramidal cells, whereas acute exposures caused modest drops in excitatory synaptic signaling in males. Ultrastructural analyses of CA1 synapses found smaller postsynaptic densities in larger spines of chronically exposed mice compared to controls and acutely exposed mice. Myelination was also affected by GCR Sim with acutely exposed mice exhibiting an increase in the percent of myelinated axons; however, the myelin sheathes on small calibur (< 0.3 mm) and larger (> 0.5 mm) axons were thinner when compared to controls. Present findings might have been predicted based on previous studies using single and mixed beam exposures and provide further evidence that space-relevant radiation exposures disrupt critical cognitive processes and underlying neuronal network-level plasticity, albeit not to the extent that might have been previously predicted.
Keywords	aggression ; central nervous system ; chronic exposure ; cognition ; electrophysiology ; females ; irradiation ; males ; memory ; myelin sheath ; myelination ; neurons ; neuroplasticity ; plasticity ; travel
Language	English
Dates of publication	2023-01
Size	p. 29.
Publishing place	Springer International Publishing
Document type	Article ; Online
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04666-8
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 47/14: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast.

Perez Garcia, Georgina / De Gasperi, Rita / Gama Sosa, Miguel A / Perez, Gissel M / Otero-Pagan, Alena / Pryor, Dylan / Abutarboush, Rania / Kawoos, Usmah / Hof, Patrick R / Dickstein, Dara L / Cook, David G / Gandy, Sam / Ahlers, Stephen T / Elder, Gregory A

Acta neuropathologica communications

2021 Volume 9, Issue 1, Page(s) 33

Abstract: Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a ... ...

Abstract	Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a neurodegenerative basis. Rats exposed to repetitive low-level blast exhibit chronic neurobehavioral traits and accumulate tau phosphorylated at threonine 181 (Thr181). Using data previously reported in separate studies we tested the hypothesis that region-specific patterns of Thr181 phosphorylation correlate with behavioral measures also previously determined and reported in the same animals. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization. There were no correlations with levels in amygdala or posterior neocortical regions. Particularly striking were asymmetrical effects on the right and left hippocampus. No systematic variation in head orientation toward the blast wave seems to explain the laterality. Levels did not correlate with behavioral measures of hyperarousal. Results were specific to Thr181 in that no correlations were observed for three other phospho-acceptor sites (threonine 231, serine 396, and serine 404). No consistent correlations were linked with total tau. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and the hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself. They also suggest an association linking blast injury with tauopathy, which has implications for understanding the relationship of chronic blast-related neurobehavioral syndromes in humans to neurodegenerative diseases.
MeSH term(s)	Animals ; Anxiety/pathology ; Anxiety/psychology ; Behavior, Animal ; Blast Injuries/complications ; Blast Injuries/pathology ; Blast Injuries/psychology ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/pathology ; Brain Injuries, Traumatic/psychology ; Disease Models, Animal ; Fear ; Functional Laterality ; Hippocampus/metabolism ; Hippocampus/pathology ; Male ; Phosphorylation ; Rats ; Rats, Long-Evans ; Stress Disorders, Post-Traumatic/complications ; Stress Disorders, Post-Traumatic/pathology ; Stress Disorders, Post-Traumatic/psychology ; tau Proteins/metabolism
Chemical Substances	tau Proteins
Language	English
Publishing date	2021-03-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-021-01128-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes.

Sharma, Rupali / Cramer, Nathan P / Perry, Bayley / Adahman, Zahra / Murphy, Erin K / Xu, Xiufen / Dardzinski, Bernard J / Galdzicki, Zygmunt / Perl, Daniel P / Dickstein, Dara L / Iacono, Diego

Scientific reports

2019 Volume 9, Issue 1, Page(s) 16406

Abstract: Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In ... ...

Abstract	Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain. Specifically, we found decreased levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, post synaptic density-95 (PSD-95) (p < 0.05), growth associated protein 43 (GAP43) (p < 0.05), glial fibrillary acidic protein (GFAP) (p < 0.05) in the cerebellum, and SYP (p < 0.05) and PSD-95 (p < 0.05) in the brainstem. Ultrastructural analyses of synaptic density and morphology in the hippocampus did not reveal any differences in CEHA mice compared to SL mice. Our data are novel and suggest that CEHA exposure leads to cognitive impairment in conjunction with neuroanatomically-based molecular changes in synaptic protein levels and astroglial cell marker in a region specific manner. We hypothesize that these new findings are part of highly complex molecular and neuroplasticity mechanisms underlying neuroadaptation response that occurs in brains when chronically exposed to HA.
MeSH term(s)	Altitude ; Animals ; Astrocytes/physiology ; Brain/physiology ; Chromosome Pairing ; Environmental Exposure/adverse effects ; Hippocampus/physiology ; Memory ; Mice ; Neuronal Plasticity
Language	English
Publishing date	2019-11-11
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-52563-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Adolescent exposure to Δ

Miller, Michael L / Chadwick, Benjamin / Dickstein, Dara L / Purushothaman, Immanuel / Egervari, Gabor / Rahman, Tanni / Tessereau, Chloe / Hof, Patrick R / Roussos, Panos / Shen, Li / Baxter, Mark G / Hurd, Yasmin L

Molecular psychiatry

2018 Volume 24, Issue 4, Page(s) 588–600

Abstract: Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in ... ...

Abstract	Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in humans has been linked to subsequent vulnerability to psychiatric disorders such as addiction and schizophrenia. Here, we investigated in a rat model the effects of adolescent exposure to Δ
MeSH term(s)	Age Factors ; Animals ; Dendrites/drug effects ; Dendritic Spines/physiology ; Dronabinol/adverse effects ; Dronabinol/metabolism ; Male ; Neuronal Plasticity/drug effects ; Neurons/drug effects ; Prefrontal Cortex/drug effects ; Prefrontal Cortex/metabolism ; Pyramidal Cells/drug effects ; Rats ; Rats, Long-Evans
Chemical Substances	Dronabinol (7J8897W37S)
Language	English
Publishing date	2018-10-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-018-0243-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4812: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats.

Jacot-Descombes, Sarah / Keshav, Neha U / Dickstein, Dara L / Wicinski, Bridget / Janssen, William G M / Hiester, Liam L / Sarfo, Edward K / Warda, Tahia / Fam, Matthew M / Harony-Nicolas, Hala / Buxbaum, Joseph D / Hof, Patrick R / Varghese, Merina

Molecular autism

2020 Volume 11, Issue 1, Page(s) 89

Abstract: Background: Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites ... ...

Abstract	Background: Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites and spines in the hippocampus, cerebellum, and striatum have been associated with behavioral impairments in Shank3-deficient animal models. Given the attentional deficit in these animals, our study explored whether deficiency of Shank3 in a rat model alters neuron morphology and synaptic ultrastructure in the medial prefrontal cortex (mPFC). Methods: We assessed dendrite and spine morphology and spine density in mPFC layer III neurons in Shank3-homozygous knockout (Shank3-KO), heterozygous (Shank3-Het), and wild-type (WT) rats. We used electron microscopy to determine the density of asymmetric synapses in mPFC layer III excitatory neurons in these rats. We measured postsynaptic density (PSD) length, PSD area, and head diameter (HD) of spines at these synapses. Results: Basal dendritic morphology was similar among the three genotypes. Spine density and morphology were comparable, but more thin and mushroom spines had larger head volumes in Shank3-Het compared to WT and Shank3-KO. All three groups had comparable synapse density and PSD length. Spine HD of total and non-perforated synapses in Shank3-Het rats, but not Shank3-KO rats, was significantly larger than in WT rats. The total and non-perforated PSD area was significantly larger in Shank3-Het rats compared to Shank3-KO rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the mPFC of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan-McDermid syndrome. Limitations: The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and would only model the effect of mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, the ultrastructural study focused only on synaptic structure in male Shank3-deficient rats. Conclusions: We observed increased HD and PSD area in Shank3-Het rats. These observations suggest the occurrence of altered synaptic ultrastructure in this animal model, further pointing to a key role of defective expression of the Shank3 protein in ASD and Phelan-McDermid syndrome.
MeSH term(s)	Animals ; Dendritic Spines/ultrastructure ; Female ; Heterozygote ; Male ; Nerve Tissue Proteins/deficiency ; Nerve Tissue Proteins/metabolism ; Post-Synaptic Density/metabolism ; Prefrontal Cortex/pathology ; Rats ; Synapses/ultrastructure
Chemical Substances	Nerve Tissue Proteins ; Shank3 protein, rat
Keywords	covid19
Language	English
Publishing date	2020-11-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2540930-X
ISSN	2040-2392 ; 2040-2392
ISSN (online)	2040-2392
ISSN	2040-2392
DOI	10.1186/s13229-020-00393-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito