The protective effect of myo-inositol on hippocamal cell loss and structural alterations in neurons and synapses triggered by kainic acid-induced status epilepticus.

It is known that myo-inositol pretreatment attenuates the seizure severity and several biochemical changes provoked by experimentally induced status epilepticus. However, it remains unidentified whether such properties of myo-inositol influence the structure of epileptic brain. In the present light and electron microscopic research we elucidate if pretreatment with myo-inositol has positive effect on hippocampal cell loss, and cell and synapses damage provoked by kainic acid-induced status epilepticus. Adult male Wistar rats were treated with (i) saline, (ii) saline + kainic acid, (iii) myo-inositol + kainic acid. Assessment of cell loss at 2, 14, and 30 days after treatment demonstrate cytoprotective effect of myo-inositol in CA1 and CA3 areas. It was strongly expressed in pyramidal layer of CA1, radial and oriental layers of CA3 and in less degree-in other layers of both fields. Ultrastructural alterations were described in CA1, 14 days after treatment. The structure of neurons, synapses, and porosomes are well preserved in the rats pretreated with myo-inositol in comparing with rats treated with only kainic acid.

Hypokinetic stress and neuronal porosome complex in the rat brain: the electron microscopic study.

Porosomes are the universal secretory machinery in cells, where membrane-bound secretory vesicles transiently dock and fuse to release intravesicular contents to the outside of the cell during cell secretion. Studies using atomic force microscopy, electron microscopy, electron density and 3D contour mapping, provided rich nanoscale information on the structure and assembly of proteins within the neuronal porosome complex in normal brain. However it remains uncertain whether pathological conditions that alter process of neurotransmission, provoke alterations in the porosome structure also. To determine if porosomes are altered in disease states, the current study was undertaken for first time using high resolution electron microscope. One of pathologies that produce subtle alteration at the presynaptic terminals has been demonstrated to be hypokinetic stress. The central nucleus of amygdale is the brain region, where such alterations are mostly expressed. We have examined the width and depth of the neuronal porosome complex and their alterations provoked by chronic hypokinetic stress in above mentioned limbic region. Specifically, we have demonstrated that despite alterations in the presynaptic terminals and synaptic transmission provoked by this pathological condition in this region, the final step/structure in neurosecretion--the porosome--remains unaffected: the morphometric analysis of the depth and diameter of this cup-shaped structure at the presynaptic membrane point out to the heterogeneity of porosome dimensions, but with unchanged fluctuation in norm and pathology.

Remodeling of heterochromatin induced by heavy metals in extreme old age.

The levels of chromosome instability and heat absorption of chromatin have been studied in cultured lymphocytes derived from blood of 80-93- and 18-30-year-old individuals, under the effect of heavy metal Cu(II) and Cd(II) salts. The analysis of the results obtained indicates that 50 µM Cu(II) induced a significantly higher level of cells with chromosome aberrations in old donors (13.8 ± 1.5% vs control, 3.8 ± 1.7%), whereas treatment with 100 µM Cd(II) did not induce any changes in the background index. Analysis of the lymphocyte melting curves showed that Cu(II) ions caused more effective condensation of heterochromatin in old healthy individuals compared with young donors, which was expressed by the increase of the T (m) of elderly chromatin by ~3°C compared with the norm. Treatment of lymphocyte chromatin of old individuals with 100 µM Cd(II) caused decondensation (deheterochromatinization) of both the facultative and constitutive domains of heterochromatin. The deheterochromatinization T (m) was decreased by ~3-3.5°C compared with the T (m) observed for young individuals. Thus, the chromatin of cultured lymphocytes from the old-aged individuals underwent modification under the influence of copper and cadmium salts. Cu(II) caused additional heterochromatinization of heterochromatin, and Cd(II) caused deheterochromatinization of facultative and constitutive heterochromatin. Our data may be important as new information on the remodeling of constitutive and facultative heterochromatin induced by heavy metals in aging, aging pathology, and pathology linked with metal ions.

Glial cells are born with synapses.

In postnatal rodent brain, certain NG2-expressing oligodendroglial precursor cells (OPCs) are contacted by synaptic terminals from local neurons. However, it has remained elusive whether and when NG2(+) cells are integrated into neuronal circuits. Here we use patch-clamp recordings from mitotic cells in murine brain slices to show that, unlike any other cell in the central nervous system (CNS), cortical NG2(+) cells divide and relocate while being linked to synaptic junctions. Together with bromodeoxyuridine (BrdU) labeling, our recordings imply that cellular processes that bear synaptic junctions are surprisingly kept during cytokinesis and are inherited by the daughter cells. Cell cycle time (78 h) and relocation speed (5 microm/day) are slowed, and NG2(+) cells largely divide symmetrically. Inheritance of synapses enables newborn glial cells to establish synaptic connections much faster than newborn neurons and ensures that the entire population of NG2(+) cells is exposed to synaptic signals from local axons. The results suggest that synapses do not only transmit neuronal activity but also act as environmental cues for the development of glial cells. Inheritance of synapses allows for the direct transfer of environmental interactions to clonal descendants of OPCs, which might be important for effective colonization and myelination of the developing brain.