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To determine the clinical significance of the Raji cell radioimmunoassay as a laboratory marker of activity, four patients with systemic lupus erythematosus (SLE) were followed for a period of 30 to 90 months. These sequential analyses did not show a correlation between circulating immune complexes, determined by Raji cell radioimmunoassay, and signs and symptoms in these lupus patients over a period of several years. We believe that the Raji cell test offers no advantage over other well known immunologic parameters used in SLE (antibodies to native DNA, complement factors C3 and C4 or CH50). In the management of SLE patients, laboratory data should not serve as a key by which to adjust treatment with prednisone or immunosuppressive drugs; clinical data are of outstanding importance in this respect.

New olfactory bulb granule cells (GCs) are GABAergic interneurons continuously arising from neuronal progenitors and integrating into preexisting bulbar circuits. They receive both GABAergic and glutamatergic synaptic inputs from olfactory bulb intrinsic neurons and centrifugal afferents. Here, we investigated the spatiotemporal dynamic of newborn GC synaptogenesis in adult mouse olfactory bulb. First, we established that GABAergic synapses onto mature GC dendrites contain the GABAAreceptor α2 subunit along with the postsynaptic scaffolding protein gephyrin. Next, we characterized morphologically and electrophysiologically the development of GABAergic and glutamatergic inputs onto newborn GCs labeled with eGFP (enhanced green fluorescent protein) using lentiviral vectors. Already when reaching the GC layer (GCL), at 3 d post-vector injection (dpi), newborn GCs exhibited tiny voltage-dependent sodium currents and received functional GABAergic and glutamatergic synapses, recognized immunohistochemically by apposition of specific presynaptic and postsynaptic markers. Thereafter, GABAergic and glutamatergic synaptic contacts increased differentially in the GCL, and at 7 dpi, PSD-95 clusters outnumbered gephyrin clusters. Thus, the weight of GABAergic input was predominant at early stages of GC maturation, but not later. Newborn GC dendrites first reached the external plexiform layer at 4 dpi, where they received functional GABAergic contacts at 5 dpi. Reciprocal synapses initially were formed on GC dendritic shafts, where they might contribute to spine formation. Their presence was confirmed ultrastructurally at 7 dpi. Together, our findings unravel rapid synaptic integration of newborn GCs in adult mouse olfactory bulb, with GABAergic and glutamatergic influences being established proximally before formation of output synapses by apical GC dendrites onto mitral/tufted cells.

The pharmacological properties of gamma-aminobutyric acidA (GABA(A)) receptors are altered by prolonged exposure to ethanol both in vivo and in vitro. We have shown previously that prolonged ethanol exposure elicits selective alterations in various GABA(A) receptor subunit mRNA levels in rat cerebral cortex. Some of these effects are rapidly reversed during ethanol withdrawal. The present study was conducted to determine the effects of prolonged ethanol exposure (dependence) and ethanol withdrawal on cerebral cortical peptide expression for several subunits. GABA(A) receptor alpha1 subunit peptide levels were decreased by nearly 40%, whereas alpha4 subunit peptide levels were increased by 27% in both ethanol-dependent and withdrawn rats. These changes correlate well with observed alterations in mRNA levels following prolonged ethanol exposure in dependent rats, but do not match the effects on mRNA levels during ethanol withdrawal. Beta2/3 subunit peptide levels increased by approximately 32% in both ethanol-dependent rats and rats undergoing ethanol withdrawal. We observed a 30-60% increase in gamma1 subunit peptide levels in both dependent rats and those undergoing withdrawal, also correlating with the previous report on ethanol-induced alterations in mRNA levels. Peptide levels for gamma2 subunits did not differ from control values in either condition. These findings show that specific alterations in GABA(A) receptor subunit peptide levels are associated with ethanol dependence in rats. GABA(A) receptor subunit peptide expression is more stable than mRNA expression, and mRNA levels are not representative of peptide expression during ethanol withdrawal. These findings are consistent with the suggestion that alterations in GABA(A) receptor gene expression underlie the functional properties of GABA(A) receptors in ethanol-dependent rats and those undergoing ethanol withdrawal.

Temporal lobe epilepsy (TLE) is associated with impaired inhibitory neurotransmission. Studies in animal models suggest that GABAAreceptor dysfunction contributes to epileptogenesis. To understand the mechanisms underlying TLE in humans, it is fundamental to determine whether and how GABAAreceptor subtypes are altered. Furthermore, identifying novel receptor targets is a prerequisite for developing selective antiepileptic drugs. We have therefore analyzed subunit composition and distribution of the three major GABAAreceptor subtypes immunohistochemically with subunit-specific antibodies (α1, α2, α3, β2,3, and γ2) in surgical specimens from TLE patients with hippocampal sclerosis (n= 16). Profound alterations in GABAAreceptor subtype expression were observed when compared with control hippocampi (n= 10). Although decreased GABAAreceptor subunit staining, reflecting cell loss, was observed in CA1, CA3, and hilus, the distinct neuron-specific expression pattern of the α-subunit variants observed in controls was markedly changed in surviving neurons. In granule cells, prominent upregulation mainly of the α2-subunit was seen on somata and apical dendrites with reduced labeling on basal dendrites. In CA2, differential rearrangement of all three α-subunits occurred. Moreover, there was layer-specific loss of α1-subunit-immunoreactive interneurons in hippocampus proper, whereas surviving interneurons exhibited extensive changes in dendritic morphology. Throughout, expression patterns of β2,3- and γ2-subunits largely followed those of α-subunit variants. These results demonstrate unique subtype-specific expression of GABAAreceptors in human hippocampus. The significant reorganization of distinct receptor subtypes in surviving hippocampal neurons of TLE patients with hippocampal sclerosis underlines the potential for synaptic plasticity in the human GABA system.