Previous studies in rat models of neurodegenerative disorders have show n disregulation of striatal synaptotagmin7 mRNA. Here w e explored the expression of synaptotagmin7 mRNA in the brains of rats w ith seizures triggered by the glutamatergic agonist kainate (10 mg/kg) or by the muscarinic agonist pilocarpine (30 mg/kg) in LiCl (3 mEq/kg) pre- treated (24 h) rats, in a time-course experiment (30 min-1 day). After kainate-induced seizures, synaptotagmin7 mRNA levels w ere transiently and uniformly increased throughout the dorsal and ventral striatum (accumbens) at 8 and 12 h, but not at 24 h, follow ed at 24 h by somew hat variable upregulation w ithin different parts of the cerebral cortex, amigdala and thalamic nuclei, the hippocampus and the lateral septum. By contrast, after LiCl/pilocarpine-induced seizures, there w as a more prolonged increase of striatal Synaptotagmin7 mRNA levels (at 8, 12 and 24 h), but only in the ventromedial striatum, w hile in some other of the aforementioned brain regions there w as a decline to below the basal levels. After systemic post-treatment w ith muscarinic antagonist scopolamine in a dose of 2 mg/kg the seizures w ere either extinguished or attenuated. In scopolamine post-treated animals w ith extinguished seizures the striatal synaptotagmin7 mRNA levels (at 12 h after the onset of seizures) w ere not different from the levels in control animals w ithout seizures, w hile in rats w ith attenuated seizures, the upregulation closely resembled kainate seizures-like pattern of striatal upregulation. In the dose of 1 mg/kg, scopolamine did not significantly affect the progression of pilocarpine-induced seizures or pilocarpine seizures-like pattern of striatal upregulation of synaptotagmin7 mRNA. In control experiments, equivalent doses of scopolamine per se did not affect the expression of synaptotagmin7 mRNA. W e conclude that here described differential time course and pattern of synaptotagmin7 mRNA expression imply regional differences of pathophysiological brain activation and plasticity in these two models of seizures.
COBISS.SI-ID: 2564687
Gama-Enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C-terminal end of the molecule. We have investigated the expression and co-localization of Gama-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of gama-enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C-terminally cleaved form of gama-enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of gama-enolase in microglial cells in response to amyloid-ß peptide (Aß) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with gama-enolase proved to be neuroprotective against Aß toxicity, however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of gama-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-ß-related neurodegeneration.
COBISS.SI-ID: 3441265
The study aimed to characterize curcumin (CCM) (fluorescent yellow curry pigment) labeling of neuronal fibrillar tau inclusions (FTIs) in representative cases of 3 main tauopathies: Alzheimer disease(AD), progressivesupranuclear palsy, and Pick disease. After identification of FTIs in hematoxylin and eosin-stained brain sections, sequential labeling and signal colocalization image analysis were used to compare CCM with thioflavineS (ThS), monoclonal antibody AT8 immunofluorescence, and Gallyas silver staining by visualizing the same FTIs. Curcumin preference for specifictau isoforms was tested with 3-repeat tau and 4-repeat tau isoform-specific immunofluorescence. Curcumin proved highly comparable to ThS and Gallyas staining in its detection of FTIs. When comparing CCM with AT8, ThS, andGallyas staining in AD and progressive supranuclear palsy, 3 types of neuronal tau deposits were observed: nonfibrillar intracellular material labeled only with AT8, fibrillar intracellular inclusions labeled byall the methods, and fibrillar extracellular FTIs labeled with CCM, ThS, and Gallyas staining but not with AT8. Although CCM labeling overlapped with both 3-repeattau and 4-repeat tau in AD, it did not label 3-repeat tau FTIs in Pickdisease probably because of their different ultrastructural characteristics. In summary, CCM fluorescence reliably detected neuronal FTIs in AD and progressive supranuclear palsy and surpassed AT8 immunolabeling in visualizing later stages ofFTIs, including ghost tangles. These results provide the basis for potential future applications of CCM binding of tau aggregates in diagnostic pathology and in vivo.
COBISS.SI-ID: 26809305
Sprouting of uninjured nociceptive axons was examined in young adult, middle aged and aged rats. Axon sprouting from the spared sural nerve, both into adjacent denervated skin and into end-to-side coapted nerve graft, was significantly higher in young rats than in aged rats. Cross-transplantations of the end-to-side coapted nerve grafts between young and aged rats demonstrated that axon sprouting from young recipient nerves into aged donor nerve grafts was significantly deteriorated, whereas the axon sprouting from aged recipient nerves into young donor nerve grafts was not statistically significantly affected. The levels of laminin polypeptides in peripheral nerves were 50-100% higher in young adult than in aged rats. However, the levels of peripherin, NGF isoforms and TrkA in skin, peripheral nerves and DRG, respectively, were not significantly reduced in aged rats. Therefore, impaired sprouting of nociceptive axons in aged rats is due rather to the alterations in peripheral neural pathways, than to the limited sprouting capacity of aged sensory neurons. Decreased levels of extracellular matrix components might be important in this respect.
COBISS.SI-ID: 24118745
In rat fast muscles, collagen Q (ColQ) expression is restricted to the neuromuscular junctions. In contrast, it is high also extrajunctionally in the slow soleus muscles. Fast muscles activated by chronic low-frequency electrical stimulation, similar to neural activation of the soleus muscles, did not increase their extrajunctional expression of ColQ. We assumed that the myogenic stem cells (satellite cells) in fast and slow muscles were intrinsically different in regard to the capacity that they convey to their respective muscle fibers to increase the extrajunctional ColQ expression upon innervation. ColQ mRNA levels were determined by quantitative real-time PCR. Extensive neural suppression of the extrajunctional ColQ expression in regenerating fast muscles during maturation is a very slow process requiring 3060 days. If the immature regenerating fast EDL muscles were indirectly or directly electrically stimulated immediately after innervation by chronic low-frequency impulse pattern for 8 days, no significant increase of the extrajunctional ColQ mRNA levels was observed in stimulated regenerates in comparison to non-stimulated ones. In contrast, the extrajunctional ColQ mRNA levels in the regenerates of the soleus muscles, trans-innervated by the EDL nerve at the time of muscle injury, increased 4- to 5- fold after 8 days of the same chronic low-frequency electrical stimulation in comparison to those in the stimulated EDL regenerates. Since both fast and slow muscles completely regenerated only from their own myogenic stem cells and were innervated by the same nerve and later activated by the same tonic pattern of impulses, these results demonstrated that the mechanism causing incapacity of regenerating fast muscles to increase their extrajunctional ColQ expression upon tonic activation is encoded in their satellite cells, which in this respect differ from those in the slow muscles.
COBISS.SI-ID: 30454745