However, immunosuppressive therapy failed to improve her
condition. When her 17-year-old sister (patient 2) also developed epilepsy, an intensified search for metabolic diseases led to the diagnosis. On electron microscopy mitochondrial abnormalities mainly affecting neurons were detected in the brain biopsy of patient 1, including an increase in number and size, structural changes and globoid inclusions. In patient Bafilomycin A1 2, light and electron microscopy on a muscle biopsy confirmed a mitochondrial myopathy, also revealing an increase in mitochondrial size and number, as well as globoid inclusions. Neurons may be the primary target of mitochondrial dysfunction in brains of patients with Alpers disease related to POLG1 mutations. During early disease stages, brain histopathology may be misleading,
showing reactive inflammatory changes. “
“S. Montori, S. Dos_Anjos, A. Poole, M. M. Regueiro-Purriños, I. L. Llorente, M. G. Darlison, A. Fernández-López and B. Martínez-Villayandre (2012) Neuropathology and Applied Neurobiology38, 710–722 Differential effect of transient global ischaemia on the levels of γ-aminobutyric acid type A (GABAA) receptor subunit mRNAs in young and older rats Aims: This study has investigated how global brain ischaemia/reperfusion (I/R) modifies levels of mRNAs encoding γ-aminobutyric acid type A (GABAA) receptor α1, β2 and γ2 subunits and glutamic acid decarboxylase 65 (GAD65) in an age- and structure-dependent manner. Gene expression in response to treatment with the anti-inflammatory agent meloxicam was also investigated. Methods: Global ischaemia was Smoothened Agonist solubility dmso induced in 3- and 18-month-old male Sprague–Dawley rats. CA1, CA3, and dentate gyrus (DG) hippocampal areas, cerebral cortex (CC) and caudate putamen (C-Pu) from sham-operated and I/R-injured animals were excised 48 h after the insult and prepared for quantitative (-)-p-Bromotetramisole Oxalate polymerase chain reaction assays. Following I/R, meloxicam treatment was also carried out on young
animals. Results: Data revealed significant decreases in the levels of all GABAA receptor subunit transcripts in the hippocampus of both young and older injured animals compared with sham-operated ones. In contrast, there was either an increase or no change in GAD65 mRNA levels. GABAA receptor subunit transcript decreases were also observed in the CC and C-Pu in young injured animals but not in the CC of the older injured ones; interestingly, significant increases were observed in the C-Pu of older injured animals compared with controls. Meloxicam treatment following the insult resulted in a diminution of the previously described I/R response. Conclusions: The data indicate that I/R results in the modification of the levels of several gene transcripts involved in GABAergic signalling in both the pre- and postsynaptic components, of this neurotransmitter system, in an age- and structure-dependent manner.