Limits...
Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican.

Howell MD, Gottschall PE - ASN Neuro (2012)

Bottom Line: Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity.In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs.In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

ABSTRACT
DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits.

Show MeSH

Related in: MedlinePlus

Correlation analysis between versican V2 in hippocampal region extracts and RAWM performance for LMC and Ts65Dn miceCorrelation between versican V2 immunoreactivity and the number of errors committed in the final block (block 12) of the RAWM for stratum oriens (A), dentate gyrus (B), and rest of hippocampus (C). Linear regression analysis was performed to determine the significance of the r2 value (see the text).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3275338&req=5

Figure 6: Correlation analysis between versican V2 in hippocampal region extracts and RAWM performance for LMC and Ts65Dn miceCorrelation between versican V2 immunoreactivity and the number of errors committed in the final block (block 12) of the RAWM for stratum oriens (A), dentate gyrus (B), and rest of hippocampus (C). Linear regression analysis was performed to determine the significance of the r2 value (see the text).

Mentions: Since spatial memory as measured in the RAWM is mediated by the hippocampus, and the presence of lecticans is important in synaptic plasticity (Frischknecht et al., 2009), we wanted to examine whether there was a correlation between altered abundance of versican V2 and performance in the RAWM. There was a correlation between increased versican and an increase in the number of errors in the final block (block 12) of the RAWM in the Ts65Dn stratum oriens (P = 0.0044, r2 = 0.9912), but not LMC stratum oriens (Figure 6A). Further, there was no correlation between versican abundance and errors in the final block of the RAWM in the Ts65Dn or LMC dentate gyrus or rest of hippocampus (Figures 6B and 6C).


Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican.

Howell MD, Gottschall PE - ASN Neuro (2012)

Correlation analysis between versican V2 in hippocampal region extracts and RAWM performance for LMC and Ts65Dn miceCorrelation between versican V2 immunoreactivity and the number of errors committed in the final block (block 12) of the RAWM for stratum oriens (A), dentate gyrus (B), and rest of hippocampus (C). Linear regression analysis was performed to determine the significance of the r2 value (see the text).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275338&req=5

Figure 6: Correlation analysis between versican V2 in hippocampal region extracts and RAWM performance for LMC and Ts65Dn miceCorrelation between versican V2 immunoreactivity and the number of errors committed in the final block (block 12) of the RAWM for stratum oriens (A), dentate gyrus (B), and rest of hippocampus (C). Linear regression analysis was performed to determine the significance of the r2 value (see the text).
Mentions: Since spatial memory as measured in the RAWM is mediated by the hippocampus, and the presence of lecticans is important in synaptic plasticity (Frischknecht et al., 2009), we wanted to examine whether there was a correlation between altered abundance of versican V2 and performance in the RAWM. There was a correlation between increased versican and an increase in the number of errors in the final block (block 12) of the RAWM in the Ts65Dn stratum oriens (P = 0.0044, r2 = 0.9912), but not LMC stratum oriens (Figure 6A). Further, there was no correlation between versican abundance and errors in the final block of the RAWM in the Ts65Dn or LMC dentate gyrus or rest of hippocampus (Figures 6B and 6C).

Bottom Line: Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity.In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs.In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

ABSTRACT
DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits.

Show MeSH
Related in: MedlinePlus