Family structure and posttraumatic stress reactions: a longitudinal study using multilevel analyses

<p>Abstract</p> <p>Background</p> <p>There is limited research on the relevance of family structures to the development and maintenance of posttraumatic stress following disasters. We longitudinally studied the effects of marital and parental statuses on posttraumatic stress reactions after the 2004 Southeast Asian tsunami and whether persons in the same households had more shared stress reactions than others.</p> <p>Method</p> <p>The study included a tourist population of 641 Norwegian adult citizens, many of them from families with children. We measured posttraumatic stress symptoms with the Impact of Event Scale-Revised at 6 months and 2 years post-disaster. Analyses included multilevel methods with mixed effects models.</p> <p>Results</p> <p>Results showed that neither marital nor parental status was significantly related to posttraumatic stress. At both assessments, adults living in the same household reported levels of posttraumatic stress that were more similar to one another than adults who were not living together. Between households, disaster experiences were closely related to the variance in posttraumatic stress symptom levels at both assessments. Within households, however, disaster experiences were less related to the variance in symptom level at 2 years than at 6 months.</p> <p>Conclusions</p> <p>These results indicate that adult household members may influence one another's posttraumatic stress reactions as well as their interpretations of the disaster experiences over time. Our findings suggest that multilevel methods may provide important information about family processes after disasters.</p

Axon-terminals expressing EAAT2 (GLT-1; Slc1a2) are common in the forebrain and not limited to the hippocampus

The excitatory amino acid transporter type 2 (EAAT2) represents the major mechanism for removal of extracellular glutamate. In the hippocampus, there is some EAAT2 in axon-terminals, whereas most of the protein is found in astroglia. The functional importance of the neuronal EAAT2 is unknown, and it is debated whether EAAT2-expressing nerve terminals are present in other parts of the brain. Here we selectively deleted the EAAT2 gene in neurons (by crossing EAAT2-flox mice with synapsin 1-Cre mice in the C57B6 background). To reduce interference from astroglial EAAT2, we measured glutamate accumulation in crude tissue homogenates. EAAT2 proteins levels were measured by immunoblotting. Although synapsin 1-Cre mediated gene deletion only reduced the forebrain tissue content of EAAT2 protein to 95.5 ± 3.4% of wild-type (littermate) controls, the glutamate accumulation in homogenates of neocortex, hippocampus, striatum and thalamus were nevertheless diminished to, respectively, 54 ± 4, 46 ± 3, 46 ± 2 and 65 ± 7% of controls (average ± SEM, n = 3 pairs of littermates). GABA uptake was unaffected. After injection of U-13C-glucose, lack of neuronal EAAT2 resulted in higher 13C-labeling of glutamine and GABA in the hippocampus suggesting that neuronal EAAT2 is partly short-circuiting the glutamate-glutamine cycle in wild-type mice. Crossing synapsin 1-Cre mice with Ai9 reporter mice revealed that Cre-mediated excision occurred efficiently in hippocampus CA3, but less efficiently in other regions and hardly at all in the cerebellum. Conclusions: (1) EAAT2 is expressed in nerve terminals in multiple brain regions. (2) The uptake catalyzed by neuronal EAAT2 plays a role in glutamate metabolism, at least in the hippocampus. (3) Synapsin 1-Cre does not delete floxed genes in all neurons, and the contribution of neuronal EAAT2 is therefore likely to be larger than revealed in the present study

Novel aspects of glutamine synthetase in ammonia homeostasis

Elevated blood ammonia (hyperammonemia) is believed to be a major contributor to the neurological sequelae following severe liver disease. Ammonia is cleared via two main mechanisms, the urea cycle pathway and the glutamine synthetase reaction. Recent studies of genetically modified animals confirm the importance of the urea cycle, but also suggest that the glutamine synthetase reaction is more important than previously recognized. While the liver clears about two-thirds of the body's ammonia via the combined action of the urea cycle and glutamine synthetase, extrahepatic tissues do not express all the components required for performing a complete urea cycle and therefore depend on the glutamine synthetase reaction for ammonia clearance. The brain is particularly vulnerable to the effects of hyperammonemia, which include impaired extracellular potassium buffering and brain edema. Moreover, the glutamine synthetase reaction is intimately linked to the metabolism of the excitatory and inhibitory neurotransmitters glutamate and gamma aminobutyric acid (GABA), implicating a key role for this enzyme in neurotransmission. This review discusses the emerging roles of glutamine synthetase in brain pathophysiology, particularly aspects related to ammonia homeostasis and hepatic encephalopathy

Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration

Glutamate-ammonia ligase (glutamine synthetase; Glul) is enriched in astrocytes and serves as the primary enzyme for ammonia detoxification and glutamate inactivation in the brain. Loss of astroglial Glul is reported in hippocampi of epileptic patients, but the mechanism by which Glul deficiency might cause disease remains elusive. Here we created a novel mouse model by selectively deleting Glul in the hippocampus and neocortex. The Glul deficient mice were born without any apparent malformations and behaved unremarkably until postnatal week three. There were reductions in tissue levels of aspartate, glutamate, glutamine and GABA and in mRNA encoding glutamate receptor subunits GRIA1 and GRIN2A as well as in the glutamate transporter proteins EAAT1 and EAAT2. Adult Glul-deficient mice developed progressive neurodegeneration and spontaneous seizures which increased in frequency with age. Importantly, progressive astrogliosis occurred before neurodegeneration and was first noted in astrocytes along cerebral blood vessels. The responses to CO2-provocation were attenuated at four weeks of age and dilated microvessels were observed histologically in sclerotic areas of cKO. Thus, the abnormal glutamate metabolism observed in this model appeared to cause epilepsy by first inducing gliopathy and disrupting the neurovascular coupling

Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus

Emerging evidence points to monocarboxylates as key players in the pathophysiology of temporal lobe epilepsy (TLE) with hippocampal sclerosis (mesial temporal lobe epilepsy, MTLE). Monocarboxylate transporters (MCT) 1 and 2, which are abundantly present on brain endothelial cells and perivascular astrocyte endfeet, respectively, facilitate the transport of monocarboxylates and protons across cell membranes. Recently, we reported that the density of MCT1 protein is reduced on endothelial cells and increased on astrocyte plasma membranes in the hippocampal formation in patients with MTLE and in several animal models of the disorder. Because the perivascular astrocyte endfeet comprise an important part of the neurovascular unit we now assessed the distribution of the MCT2 in hippocampal formations in TLE patients with (MTLE) or without hippocampal sclerosis (non-MTLE). Light microscopic immunohistochemistry revealed significantly less perivascular MCT2 immunoreactivity in the hippocampal formation in MTLE (n=6) than in non-MTLE (n=6) patients, and to a lesser degree in non-MTLE than in non-epilepsy patients (n=4). Immunogold electron microscopy indicated that the loss of MCT2 protein occurred on perivascular astrocyte endfeet. Interestingly, the loss of MCT2 on astrocyte endfeet in MTLE (n=3) was accompanied by an upregulation of the protein on astrocyte membranes facing synapses in the neuropil, when compared with non-MTLE (n=3). We propose that the altered distribution of MCT1 and MCT2 in TLE (especially MTLE) limits the flux of monocarboxylates across the blood brain barrier and enhances the exchange of monocarboxylates within the brain parenchyma