Biomedical subjects

F C Zhou

Publications and source records attributed to F C Zhou.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Mesolimbic dopamine system in alcohol-preferring rats.

The mesolimbic dopamine system of the brain, in particular the nucleus accumbens (Acb), is long known to be involved in reward behavior. When compared with the alcohol-nonpreferring NP rats, the alcohol-preferring P rats exhibit lower dopamine (DA) levels in the Acb as well as in other forebrain areas (20). In the present study, the DA innervation density, as determined by tyrosine hydroxylase (TH) immunostaining, was found lower in the selective cingulum cortex and the shell of the Acb of the P compared with that of NP rats. These structures cluster in the medial aspect of the mesolimbic system. There were no differences in other major DA mesolimbic brain regions. The subpopulation of DA neurons in the ventral tegmental area (VTA) projecting to the Acb was found to be smaller in the P than in the NP rats, as shown by horseradish peroxidase tracing and TH immunocytochemistry double staining. However, the total number of the DA neurons in the VTA, the major mesolimbic DA center, was found to be similar in the P and NP rats. These results indicate a selective reduction of catecholaminergic innervation in the dopaminergic medial mesolimbic system in the P rats and suggest that the P and NP rat lines should be a useful model for the investigation of DA involvement in alcohol drinking as well as other reinforced behaviors.

Alcohol Drinking↗

PubMedDate not supplied

Immunostained serotonergic fibers are decreased in selected brain regions of alcohol-preferring rats.

The levels of serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) are decreased in the hippocampus, nucleus accumbens, and cortex of selectively bred alcohol-preferring (P) rats, compared with the alcohol-nonpreferring (NP) rats. In this study, we have confirmed these findings by immunocytochemistry and quantitative image analysis which indicates that there is a reduction of 5-HT immunostained fibers in several brain areas of alcohol-naive P rats. Three major areas possibly related to alcohol drinking, hippocampus, accumbens, and cortex, were examined. Pathways to these areas were also examined. The 5-HT fiber bundles had the same pattern in P and NP rats. However, in the terminal regions of the ventral hippocampus, the amount of 5-HT fibers was reduced in P rats as compared with NP rats. The 5-HT fibers in the hilus and CA4 of the dentate gyrus were also significantly decreased in the P rats. No differences in fiber density were seen in the anterior nucleus accumbens, but a significant decrease was seen in the middle medial and posterior accumbens of P rats. In the cortical regions examined, decreases in 5-HT fibers were observed in the posterior cingulum and anterior frontal cortex, but not in the insular frontal cortex of P rats. These observations indicate that there are quantitative decreases in 5-HT innervations or that the 5-HT in some 5-HT fibers is reduced to a level undetectable by immunocytochemistry in the brains of P rats when compared with that of NP rats.

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PubMedDate not supplied

Long-term nonpassaged EGF-responsive neural precursor cells are stem cells.

We have screened lines of nonpassaged epidermal growth factor-responsive neurospheres from embryonic striatum and brainstem. They have been maintained in defined medium with epidermal growth factor over a period of 2 years and remained in an undifferentiated state to this date. Since isolation from the brain 2 years ago, these nonpassaged epidermal growth factor responsive neurospheres have shown active proliferation and self-renewal capacity. When subplated on a poly-D-lysine coated surface, they resumed differentiation within 24 hours. The differentiation process of the nonpassaged epidermal growth factor responsive neurosphere appeared to recapitulate the neural development in the brain. Many cells migrated, extending radial processes while expressing nestin and S100 in the early 7-day subplating culture. They continued to differentiate into major neural types in 14-day subplating culture, including fibrous and cytoplasmic astrocytes, oligodendrocytes, and serotonin, gamma-aminobutyric acid, and a small number of tyrosine hydroxylase-positive neurons. The nonpassaged epidermal growth factor-responsive neurospheres in many ways resemble hemopoietic cells. Both are proliferative, possess the potential of indefinite self-renewal, yet multipotent, and are capable of resuming the differential pathway. The nonpassaged epidermal growth factor responsive neurospheres meet the criteria of stem cells and have been found to be a useful model to study the development in vitro.

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PubMedDate not supplied

Excitochemical-induced trophic bridging directs axonal growth of transplanted neurons to distal target.

Brain grafts directly placed in their target regions often lack proper connections and normal regulation. When brain grafts are placed in their ontogenetic normal area, the axonal outgrowth of grafts to distal target regions is a major obstacle. We previously demonstrated that directional axonal growth of grafts can be facilitated by laminin. In this study we demonstrated that excitochemicals induced trophic environment can be strategically used as a bridge to guide transplanted neurons to innervate a distal target of millimeter distance, and has a unique effect on fiber expansion in the target region. To distinguish dopamine (DA) growth from that of transplants, 6-hydroxydopamine was unilaterally injected into medial forebrain bundle to remove dopamine innervation to the striatum. Ibotenic acid (IB), kainic acid (KA), or phosphate buffer (vehicle) were microinjected through a glass-pipet to make a 7 mm long tract between the substantia nigra and the striatum in Sprague-Dawley rats. Gestational 14-15 days brainstem slurry was transplanted either in the same or a separate tract into nigra at the bottom of the bridge. All transplants survived with abundant serotonin (5-HT) and DA neurons. Traceable DA fibers formed distinct bundles from grafts along the length of IB/KA tracts. Upon arrival at their major target regions, fibers from bundles were capable of leaving the tracts, and reinnervating the DA-vacated striatum. The 5-HT fibers formed bundles similar to DA fibers but left the tract earlier upon arrival at their major target the globus pallidus and when arriving at the striatum and cortex. Fibers from grafts with vehicle tracts grew randomly and not into the tract. These results indicate that the trophic effects of chemical lesioning serves as a remarkably effective axonal guidance for more than one type of fetal neuron to innervate distal brain regions. This method has great potential in directing fibers in many transplant models.

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PubMedDate not supplied

Morphological differentiation of astroglial progenitor cells from EGF-responsive neurospheres in response to fetal calf serum, basic fibroblast growth factor, and retinol.

Procurement of multipotential neuroglial stem cells is possible with the addition of epidermal growth factor (EGF). Stem cells will differentiate into neurons and glia upon the removal of EGF from the culture medium. We have previously characterized the neuronal differentiation of stem cells derived from long-term cultured nonpassage neurospheres. In the current study, we (1) characterize the morphological differentiation of the astroglial progenitor cell from 3-mo-old neurospheres, (2) examine whether the astroglial progenitor cells from neurospheres of different brain areas exhibit different differentiation responses to the same exogenous signals, and (3) test the effects of basic fibroblast growth factor (bFGF) and retinol on differentiation. Cerebral cortex, striatum, and mesencephalon cells were obtained from Embryonic Day 14 (E-14) rat fetuses and were dissociated for the procurement of neurospheres in chemically defined medium supplemented with EGF. After 3 mo in culture, the neurospheres, derived from each of the three brain areas, were subcultured into three groups on chamber slides: (1) basal medium, (2) the basal medium plus 20 ng/mL bFGF, and (3) the basal medium plus 10 muM retinol. Phenotypic expression of astroglial cells was examined after 14 days subculture. Our findings indicate that the 3-mo-old cultured nonpassage neurospheres contained numerous multipotential stem cells that stained positive with nestin, and that environmental factors played an important role in influencing the differentiation of astroglial progenitor cells. As detected by glial fibrillary acid protein (GFAP), astroglial progenitor cells turned into protoplasmic astrocytes in the FCS-containing basal medium, fibrous astrocytes in the presence of bFGF, and spindle-shaped astrocytes in the presence of retinol. There were no noticeable differences in differentiation among astroglial progenitor cells of the various brain region-derived neurospheres in any of the three medium conditions. Peculiar varicosity-and growth cone-like structures on the long slender GFAP-positive processes suggest that neuroblasts and glioblast may share common morphologies, features, or common progenitor cells during initial differentiation in vitro.

Animals↗

PubMedDate not supplied

Laminin facilitates and guides fiber growth of transplanted neurons in adult brain.

Laminin has been shown in vitro to act as a surface adhesive molecule for neuronal process elongation. To test whether laminin has a similar role in the brain, we sequentially injected laminin and transplanted fetal neurons into various brain regions to determine if the fetal neurons would preferentially grow along a laminin injection tract. In the fetal brain, the raphe area of the rostral rhombencephalon is rich in serotonergic (5-HT) neurons; the rostral ventral mesencephalon is rich in dopamine (DA) neurons, while the lateral rhombencephalon is rich in norepinephrinergic (NE) neurons. These three areas were transplanted to the motor cortex, neostriatum or hippocampus of adult animals. The tract used for microinjection of cell suspension was then immediately filled with laminin in a suspension media or a laminin-collagen (type IV) mixture. In other animals, laminin or control solution was injected in a separate needle tract displaced 0.3-1 mm from the transplant injection tract. Straight and thick 5-HT, DA or NE immunoreactive (IR) fibers (stained with anti-5-HT or anti-tyrosine hydroxylase antiserum) were predominant within the laminin-treated tracts, or were directed toward the laminin-treated parallel tracts when it was positioned less than 0.5 mm from the transplant site. The density of 5-HT-, DA- and NE-IR fibers in the injection tracts in all three brain areas was much higher for laminin and laminin-collagen mixture than control media. Thin axonal fibers of fetal 5-HT and NE neurons were observed surrounding the laminin-treated tracts, but not around vehicle-injected tracts. In addition, a number of transplanted 5-HT, DA and NE neuronal cell bodies were seen within the laminin-treated tracts, but not in vehicle-treated tracts. Finally, laminin injection to the hippocampus, motor cortex or neostriatum of the adult brain did not stimulate sprouting of undamaged adult 5-HT or NE fibers. These results suggest that purified laminin can facilitate and guide process outgrowth of 5-HT, DA and NE neurons during early developmental stage, but does not induce sprouting on these same fiber types in the adult brain.

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