The d2 glutamate receptors are prominently expressed in Pur- kinje cells and are thought to play ... more The d2 glutamate receptors are prominently expressed in Pur- kinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of d receptors in rat cerebellar cortex was investi- gated with sensitive and high-resolution immunogold proce- dures. After postembedding incubation with an antibody raised to a C-terminal peptide of
Proceedings of the National Academy of Sciences, 2003
The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astr... more The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to α-syntrophin, an adapter protein associated with dystrophin. To test functions of the perivascular AQP4 pool, we studied mice homozygous for targeted disruption of the gene encoding α-syntrophin (α- Syn −/− ). These animals show a marked loss of AQP4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial end-feet were swollen in brains of α- Syn −/− mice compared to WT mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in α- Syn −/− mice, indicative of reduced water influx. Surprisingly, AQP4 wa...
Proceedings of the National Academy of Sciences, 2006
The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critical... more The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because such changes would determine the time course of edema formation. Here we demonstrate by quantitative immunogold cytochemistry that the ischemic striatum and neocortex show distinct patterns of AQP4 expression in the reperfusion phase after 90 min of middle cerebral artery occlusion. The striatal core displays a loss of perivascular AQP4 at 24 hr of reperfusion with no sign of subsequent recovery. The most affected part of the cortex also exhibits loss of perivascular AQP4. This loss is of magnitude similar to that of the striatal core, but it shows a partial recovery toward 72 hr of reperfusion. By freeze fracture we show that the...
Proceedings of the National Academy of Sciences, 2005
An abnormal accumulation of extracellular K + in the brain has been implicated in the generation ... more An abnormal accumulation of extracellular K + in the brain has been implicated in the generation of seizures in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Experimental studies have shown that clearance of extracellular K + is compromised by removal of the perivascular pool of the water channel aquaporin 4 (AQP4), suggesting that an efficient clearance of K + depends on a concomitant water flux through astrocyte membranes. Therefore, we hypothesized that loss of perivascular AQP4 might be involved in the pathogenesis of MTLE. Whereas Western blot analysis showed an overall increase in AQP4 levels in MTLE compared with non-MTLE hippocampi, quantitative ImmunoGold electron microscopy revealed that the density of AQP4 along the perivascular membrane domain of astrocytes was reduced by 44% in area CA1 of MTLE vs. non-MTLE hippocampi. There was no difference in the density of AQP4 on the astrocyte membrane facing the neuropil. Because anchoring of AQP4 t...
Light-and electronmicroscopic distribution of taurine, an organic osmolyte, in rat renal tubule c... more Light-and electronmicroscopic distribution of taurine, an organic osmolyte, in rat renal tubule cells. Several lines of evidence suggest that taurine acts as an organic osmolyte in the kidney. We investigated the cellular and subcellular distribution of this amino acid in rat ...
The d2 glutamate receptors are prominently expressed in Pur- kinje cells and are thought to play ... more The d2 glutamate receptors are prominently expressed in Pur- kinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of d receptors in rat cerebellar cortex was investi- gated with sensitive and high-resolution immunogold proce- dures. After postembedding incubation with an antibody raised to a C-terminal peptide of
Proceedings of the National Academy of Sciences, 2003
The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astr... more The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to α-syntrophin, an adapter protein associated with dystrophin. To test functions of the perivascular AQP4 pool, we studied mice homozygous for targeted disruption of the gene encoding α-syntrophin (α- Syn −/− ). These animals show a marked loss of AQP4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial end-feet were swollen in brains of α- Syn −/− mice compared to WT mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in α- Syn −/− mice, indicative of reduced water influx. Surprisingly, AQP4 wa...
Proceedings of the National Academy of Sciences, 2006
The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critical... more The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because such changes would determine the time course of edema formation. Here we demonstrate by quantitative immunogold cytochemistry that the ischemic striatum and neocortex show distinct patterns of AQP4 expression in the reperfusion phase after 90 min of middle cerebral artery occlusion. The striatal core displays a loss of perivascular AQP4 at 24 hr of reperfusion with no sign of subsequent recovery. The most affected part of the cortex also exhibits loss of perivascular AQP4. This loss is of magnitude similar to that of the striatal core, but it shows a partial recovery toward 72 hr of reperfusion. By freeze fracture we show that the...
Proceedings of the National Academy of Sciences, 2005
An abnormal accumulation of extracellular K + in the brain has been implicated in the generation ... more An abnormal accumulation of extracellular K + in the brain has been implicated in the generation of seizures in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Experimental studies have shown that clearance of extracellular K + is compromised by removal of the perivascular pool of the water channel aquaporin 4 (AQP4), suggesting that an efficient clearance of K + depends on a concomitant water flux through astrocyte membranes. Therefore, we hypothesized that loss of perivascular AQP4 might be involved in the pathogenesis of MTLE. Whereas Western blot analysis showed an overall increase in AQP4 levels in MTLE compared with non-MTLE hippocampi, quantitative ImmunoGold electron microscopy revealed that the density of AQP4 along the perivascular membrane domain of astrocytes was reduced by 44% in area CA1 of MTLE vs. non-MTLE hippocampi. There was no difference in the density of AQP4 on the astrocyte membrane facing the neuropil. Because anchoring of AQP4 t...
Light-and electronmicroscopic distribution of taurine, an organic osmolyte, in rat renal tubule c... more Light-and electronmicroscopic distribution of taurine, an organic osmolyte, in rat renal tubule cells. Several lines of evidence suggest that taurine acts as an organic osmolyte in the kidney. We investigated the cellular and subcellular distribution of this amino acid in rat ...
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