Defective cerebral gamma-aminobutyric acid-A receptor density in patients with systemic lupus erythematosus and central nervous system involvement. An observational study.
Gamma-aminobutyric acid-A (GABA-A) receptors play a crucial role in regulating neuronal excitability and cognitive functions. Single-photon emission computerized tomography (SPECT) analysis of GABA-A receptors binding by (123)I-labelled Iomazenil ((123)I-IMZ) has been applied in some neuropsychiatric disorders to investigate conditions where GABA-A receptor density can be detected in several pathophysiological conditions. In this study we investigate cerebral GABA-A receptor density in a small series of patients with systemic lupus erythematosus (SLE) and cognitive impairment characterized by recurrent, episodic memory loss. Nine female patients with SLE and cognitive alterations underwent to a clinical neuropsychiatric evaluation including digital video-EEG, brain MRI, (99m)Tc-ECD brain SPECT and (123)I-IMZ brain SPECT. All patients tested showed diffuse or focal GABA-A receptor density reduction. This is, to our knowledge, the first report on GABA-A receptor density abnormalities associated with cognitive defects in SLE patients. We hypothesize that in our series a decrease in GABA-A receptor density might be related to the neurological manifestations. Further studies are needed to clarify this aspect and the possible mechanisms. GABA-A receptor density impairment might be due to the SLE-related cerebral vasculopathy, or to neuronal-reacting auto-antibodies or drugs which could interfere with GABA-A receptors expression/binding. This study may support the concept that cognitive impairment in systemic lupus erythematosus could be the outcome of fine-tuned neurotransmission alterations.
Mathieu
A
A
Chair and AOU Unit of Rheumatology, University of Cagliari, Italy. mathieu@medicina.unica.it
Vacca
A
A
Serra
A
A
Cauli
A
A
Piga
M
M
Porru
G
G
Marrosu
F
F
Sanna
G
G
Piga
M
M
D000328:Adult; D002490:Central Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology; D004569:Electroencephalography; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011247:Pregnancy; D019275:Radiopharmaceuticals / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil