Vesicular glutamate transporter and cognition in stroke: a case-control autopsy study.

Abstract

OBJECTIVES:

Vascular dementia (VaD) accounts for approximately 15%-20% of all dementias, but the relationship of progressive cognitive impairment to neurochemical changes is poorly understood. We have therefore investigated glutamatergic synaptic markers in VaD.

METHODS:

We used homogenates prepared from gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and Western blotting to determine the concentrations of key components of the glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1) and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular disease with and without dementia, 10 patients with AD, and 15 controls-in a case-control design.

RESULTS:

VGLUT1 concentrations in BA 20 and BA 9 were correlated with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27). VGLUT1 concentration in BA 9 differed between the different dementia groups and the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and Bonferroni p < 0.01 in each case), with subjects with stroke who did not develop dementia exhibiting the highest mean value for VGLUT1.

CONCLUSIONS:

These data suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer disease but the preservation of synapses, in particular glutamatergic synapses, in the frontal cortex against the temporal cortex plays a role in sustaining cognition and protecting against dementia following a stroke.

• Authors: S L Kirvell, M S Elliott, R N Kalaria, T Hortobágyi, C G Ballard, P T Francis
• Journal: Neurology (Neurology) Vol. 75 Issue 20 Pg. 1803-9 (Nov 16 2010) ISSN: 1526-632X [Electronic] United States
• PMID: 21079182 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SLC17A7 protein, human
• Vesicular Glutamate Transport Protein 1

Topics

• Aged
• Aged, 80 and over
• Autopsy
• Case-Control Studies
• Cognition Disorders (etiology, metabolism, pathology)
• Dementia, Vascular (etiology, metabolism, pathology)
• Disease Progression
• Female
• Frontal Lobe (metabolism, pathology)
• Humans
• Male
• Presynaptic Terminals (metabolism, pathology)
• Stroke (complications, metabolism, pathology)
• Vesicular Glutamate Transport Protein 1 (biosynthesis, metabolism)