Glycosaminoglycan levels and proteoglycan expression are altered in the hippocampus of patients with mesial temporal lobe epilepsy.
Extracellular matrix proteoglycans (PGs) and glycosaminoglycans (GAGs) play a crucial role in cell differentiation and synaptogenesis by modulating neurite outgrowth. The chondroitin sulfate (CS)-rich PG, the receptor protein tyrosine phosphatase zeta/beta (RPTP zeta/beta), has been related to neural morphogenesis and axon guidance. Hippocampal sclerosis is the most frequent pathologic finding in patients with intractable mesial temporal lobe epilepsy (MTLE), which is associated with neuron loss, reactive gliosis, and mossy fiber sprouting. In the present study, we investigated the concentration of CS, heparan sulfate (HS) and hyaluronic acid (HA) in the hippocampus and temporal neocortex as well as RPTP zeta/beta expression in the hippocampus of patients with MTLE. Compared to autopsy control tissue, epileptic hippocampi showed a significantly increased concentration of CS (224%; p=0.0109) and HA (146%; p=0.039). HS was instead similar to control values. No differences were found in the concentration of CS, HS, or HA in the temporal neocortex of epileptic patients when compared to control values. In contrast, RPTP zeta/beta immunoreactivity was induced in astrocytes of the inner molecular layer of the dentate gyrus of the sclerotic hippocampus. Because matrix compounds have been associated with tissue injury and repair, the present findings suggest that changes in PGs and GAGs might be related to damage-induced gliosis and neuronal reorganization in the hippocampus of MTLE patients.
Perosa
S R
SR
Department of Neurology, UNIFESP-EPM, SP, São Paulo, Brazil.
Porcionatto
M A
MA
Cukiert
A
A
Martins
J R M
JR
Passeroti
C C
CC
Amado
D
D
Matas
S L A
SL
Nader
H B
HB
Cavalheiro
E A
EA
Leite
J P
JP
Naffah-Mazzacoratti
M G
MG
D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D012598:Sclerosis
D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D009419:Nerve Tissue Proteins; D017027:Protein Tyrosine Phosphatases; D011509:Proteoglycans; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; C516895:PTPRZ1 protein, human