Hilar interneuron vulnerability distinguishes aged rats with memory impairment

Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.     

Long‐term course of substantia nigra hyperechogenicity in Parkinson's disease

A hyperechogenicity of the (SN+) in transcranial sonography corroborates the diagnosis of idiopathic Parkinson's disease (iPD). Although it is thought to represent a biomarker of the disease that is independent of disease severity and progression, differing results have been reported describing a positive correlation of the size and advancing clinical stage. In 50 parkinsonian patients, transcranial ultrasound and clinical examination was performed twice with a mean time interval of 6.4 years. SN+ did not change in size significantly between the first and second examination, whereas clinical parkinsonian symptoms—as determined by the motor part of the UPDRS—significantly worsened (P < 0.001). We found a highly significant intraindividual correlation in SN+ sizes between both examinations (P < 0.001). The size of SN+ did not correlate with the UPDRS part III at the time of first or second ultrasound examination. Progression of motor symptoms between the first and second investigation did not correlate with the size of SN+ at baseline. Furthermore, even in the subgroup of patients with an interval of ≥8 years between examinations, there was no significant change in SN+ size. SN+ represents a largely stable biomarker in iPD and does not reflect disease progression. The size of SN+ does not predict the further course of the disease. © 2012 Movement Disorder Society     

The intracellular sites of early replication and budding of SARS-coronavirus

In this study, we analyzed the replication and budding sites of severe acute respiratory syndrome coronavirus (SARS-CoV) at early time points of infection. We detected cytoplasmic accumulations containing the viral nucleocapsid protein, viral RNA and the non-structural protein nsp3. Using EM techniques, we found that these putative viral replication sites were associated with characteristic membrane tubules and double membrane vesicles that most probably originated from ER cisternae. In addition to its presence at the replication sites, N also accumulated in the Golgi region and colocalized with the viral spike protein. Immuno-EM revealed that budding occurred at membranes of the ERGIC (ER-Golgi intermediate compartment) and the Golgi region as early as 3 h post infection, demonstrating that SARS-CoV replicates surprisingly fast. Our data suggest that SARS-CoV establishes replication complexes at ER-derived membranes. Later on, viral nucleocapsids have to be transported to the budding sites in the Golgi region where the viral glycoproteins accumulate and particle formation occurs.