Enikő Račeková

The Number of Proliferating Cells in the Rostral Migratory Stream of Rat During the First Postnatal Month

SUMMARYThe objective of this study was to analyze neurogenesis in the rat rostral migratory stream (RMS) during the first postnatal month.1. During the early postnatal development some morphological changes, concerning the RMS thickness, shape, and the olfactory ventricle persistence at P0 were observed.2. Bromodeoxyuridine (BrdU) immunohistochemistry and subsequent quantification of proliferating cells showed significant age-dependent changes. The highest number of proliferating cells was found at P3 and significant decrease of BrdU-positive cells at P7 rats. At P28, the number of proliferating cells reached the level of P0 rats.

Effects of short-duration electromagnetic radiation on early postnatal neurogenesis in rats: Fos and NADPH-d histochemical studies.

The immediate effects of whole body electromagnetic radiation (EMR) were used to study postnatal neurogenesis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of Wistar rats of both sexes. Newborn postnatal day 7 (P7) and young adult rats (P28) were exposed to pulsed electromagnetic fields (EMF) at a frequency of 2.45 GHz and mean power density of 2.8 mW/cm(2) for 2 h. Post-irradiation changes were studied using immunohistochemical localization of Fos and NADPH-d. We found that short-duration exposure induces increased Fos immunoreactivity selectively in cells of the SVZ of P7 and P28 rats. There were no Fos positive cells visible within the RMS of irradiated rats. These findings indicate that some differences exist in prerequisites of proliferating cells between the SVZ and RMS regardless of the age of the rats. Short-duration exposure also caused praecox maturation of NADPH-d positive cells within the RMS of P7 rats. The NADPH-d positive cells appeared several days earlier than in age-matched controls, and their number and morphology showed characteristics of adult rats. On the other hand, in the young adult P28 rats, EMR induced morphological signs typical of early postnatal age. These findings indicate that EMR causes age-related changes in the production of nitric oxide (NO), which may lead to different courses of the proliferation cascade in newborn and young adult neurogenesis.

Peripheral nerve injury influences the disinhibition induced by focal ischaemia in the rat motor cortex.

Photothrombotic lesions were produced in the rat primary motor cortex, and the brain excitability was assessed in a paired-pulse stimulation protocol by transcranial recording, in parallel at 16 points of the frontal cortex, including the insulted and the surrounding areas. The cortical lesion reduced the inhibition in the extended frontal cortex, with a delay of a few minutes. Unilateral facial nerve transection, however, accelerated the widespread disinhibition. Although the mechanism is not clear in detail, both peripheral and central injury-induced disinhibition may have a significant impact on the recovery of the function.

Odor enrichment influences neurogenesis in the rostral migratory stream of young rats

The olfactory bulb is one of a few brain structures characterized by high plasticity due to the fact that new neurons are continually integrated into the olfactory bulb circuit throughout life. The new cells originate from the subventricular zone of the forebrain and migrate through the rostral migratory stream (RMS) to the olfactory bulb that also represents the first synaptic relay of the olfactory system. Data accumulating in recent years have confirmed that sensory inputs can influence the level of postnatal neurogenesis in the olfactory bulb. In this study, we studied neurogenesis in the rostral migratory stream of Wistar albino rat pups after exposure to an odor-enriched environment. The rats were olfactory stimulated twice daily with different odorants from the day of their birth up to 1, 2 or 3 weeks, respectively. Using bromodeoxyuridine, a marker of cell proliferation, we found an increased number of proliferating cells in the rostral migratory stream of rat pups submitted to olfactory stimulation. Conversely, the number of dying cells, labeled with the fluorescent dye Fluoro Jade-C, was down-regulated in groups of rats exposed to an odor-enriched environment.

Immunohistochemical evidence for the presence of synaptic connections of nitrergic neurons in the rat rostral migratory stream.

The rostral migratory stream (RMS) is a migration route for neuroblasts originating in the richest neurogenic niche of the adult mammalian brain—the subventricular zone. Most studies are focused on cellular dynamics of migrating neuroblasts and interactions between neuroblasts and astrocytes which both represent the major cellular component of the RMS. Our previous experiments have brought evidence about the existence of a small population of mature neurons in the adult rat RMS with capacity to produce nitric oxide (NO). In order to further support functional significance of nitrergic cells, the aim of the present study was to determine whether NO producing neurons could form synapses. Sagittal sections from the adult rat brain were processed for simultaneous immunohistochemical detection of neuronal nitric oxide synthase (nNOS), the enzyme present in NO producing cells and synaptophysin, a glycoprotein found in synaptic vesicles. Synaptophysin positivity in the RMS was significantly lower in comparison with other brain areas, but its colocalization with nNOS-positive neurons was obvious. Our results suggest that nitrergic neurons in the RMS could be involved in a neuronal circuitry with potential impact on regulation of neurogenesis in the RMS.

Diverse effect of different odor stimuli on behavior and Fos protein production in the olfactory system neurogenic region of adult rats.

Previously it has been demonstrated that processes of postnatal neurogenesis in the olfactory system neurogenic region-the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB) can be significantly altered by different factors of an environment. However, the mechanisms involved in regulation of neurogenesis by exogenous factors in the olfactory system remain unclear. The purpose of the present study was to contribute to the understanding of these mechanisms by immunohistochemical assessment of Fos protein induction in areas of adult neurogenesis. To evaluate the coordinate activation of Fos production in neurons of the olfactory system neurogenic region, a brief exposure to artificial odor (eau de Cologne) or naturalistic odor (cat odor) has been used in alert rats. Our results revealed that the effects of these odors are easily distinguishable at both the behavioral and the morphological level. Cat odor induced greater changes in anxiety level, and produced typical pattern of Fos activation in the accessory olfactory bulb (AOB), a brain region associated with defensive behavior. An important finding is, that next to distinct Fos expression in the OB and the AOB, Fos positive cells have been found also within the SVZ/RMS of the odor stimulated rats. Interestingly, Fos expression in the RMS was detected only after exposure to artificial odor stimulus. These results provide new evidence that some SVZ/RMS cells have complete prerequisites necessary for the Fos signal transduction cascade.

Early stress affects neurogenesis in the rat rostral migratory stream

Stressful experience during the early postnatal period may influence processes associated with neurogenesis (i.e. proliferation, cell death, appearance of astrocytes or cell differentiation) in the neonatal rat rostral migratory stream (RMS). To induce stress, pups were subjected to maternal deprivation daily for three hours, starting from the first postnatal day till the seventh postnatal day. Immunohistochemical methods were used to visualize proliferating cells and astrocytes; dying cells and nitrergic cells were visualized using histochemical staining. Quantitative analysis showed that maternal deprivation decreased the number of proliferating cells and significantly increased the number of dying cells in the RMS. Maternal deprivation did not influence the appearance of astrocytes in the RMS, but caused premature differentiation of nitrergic cells. In control rats, nitrergic cells can be observed in the RMS as early as the tenth postnatal day. In maternally deprived pups, these cells were detected as early as the seventh postnatal day. The observed earlier appearance of nitrergic cells in the RMS was associated with altered proliferation and increased cell dying and this observation supports the hypothesis that nitric oxide has an anti-proliferative role in the RMS. Our study demonstrates that maternal deprivation represents a stressful condition with a profound impact on early postnatal neurogenesis.

Analysis of Fos expression in the rat olfactory neurogenic regionfollowing single exposure to maternal separation during differentneonatal stages

Accumulating evidence confirms that the exposure of neonatal rats to maternal separation can significantly alter individual processes of postnatal neurogenesis in the olfactory neurogenic region - the subventricular zone (SVZ) and the rostral migratory stream (RMS). To establish the stressful influence of MS on postnatal neurogenesis we have investigated whether altered olfactory environment caused by short-term MS induces expression of Fos protein in the SVZ/RMS and in the olfactory cortical area - anterior olfactory nucleus (AON) of neonatal rats. Pups were separated from mothers for 2 hours at the postnatal days 7, 14 and 21. Immunohistochemically labeled Fos protein was assessed. Our results revealed that single exposure to MS is a stressful event that selectively and in age-dependent manner stimulates cellular activity in the SVZ and AON. A few Fos+ cells were found in the SVZ of P21 control animals and MS significantly increased their number. This suggests that some SVZ cells are included in the circuitry, which is activated by MS and that these cells have complete equipment for the Fos signal transduction. MS significantly increased the number of Fos+ cells in the AON in all age stages examined suggesting that its effect is mediated by olfaction.