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  • 1.
    Berglöf, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Small, Brent J
    School of Aging Studies, University of South Florida, Tampa, Florida 33620.
    Bickford, Paula C
    Department of Neurosurgery and Department of Molecular Pharmacology and Physiology, University of South Florida and James A. Haley VA Medical Center, Tampa, Florida 33620.
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Beneficial effects of antioxidant-enriched diet for tyrosine hydroxylase-positive neurons in ventral mesencephalic tissue in oculo grafts2009In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 515, no 1, p. 72-82Article in journal (Refereed)
    Abstract [en]

    Supplementation of antioxidants to the diet has been proved to be beneficial in aging and after brain injury. Furthermore, it has been postulated that the locus coeruleus promotes survival of dopamine neurons. Thus, this study was performed to elucidate the effects of a blueberry-enriched diet on fetal ventral mesencephalic tissue in the presence or absence of locus coeruleus utilizing the in oculo grafting method. Sprague-Dawley rats were given control diet or diet supplemented with 2% blueberries, and solid tissue pieces of fetal locus coeruleus and ventral mesencephalon were implanted as single and co-grafts. The results revealed that the presence of locus coeruleus tissue or the addition of blueberries enhanced the survival of ventral mesencephalic tyrosine hydroxylase (TH)-positive neurons, whereas no additive effects were observed for the two treatments. The density of TH-positive nerve fibers in ventral mesencephalic tissue was significantly elevated when it was attached to the locus coeruleus or by blueberry treatment, whereas the innervation of dopamine-beta-hydroxylase-positive nerve fibers was not altered. The presence of locus coeruleus tissue or bluberry supplementation reduced the number of Iba-1-positive microglia in the ventral mesencephalic portion of single and co-grafts, respectively, whereas almost no OX6 immunoreactivity was found. Furthermore, neither the attachment of ventral mesencephalic tissue nor the addition of blueberries improved the survival of TH-positive neurons in the locus coerulean grafts. To conclude, locus coeruleus and blueberries are beneficial for the survival of fetal ventral mesencephalic tissue, findings that could be useful when grafting tissue in Parkinson's disease.

  • 2.
    Novikova, Liudmila N
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellerth, J O
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats2000In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 428, no 4, p. 671-680Article in journal (Refereed)
    Abstract [en]

    Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have previously been shown to support survival and axonal regeneration in various types of neurons. Also, synergistic neuroprotective effects of these neurotrophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons of Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neurons had been lost, and the remaining cells exhibited marked atrophy. Microglial activity was significantly increased in CN of the operated side. Intrathecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell survival and a reduction in cell atrophy, but did not reduce microglial activity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffective. Furthermore, when a combination of BDNF and NT-3 was administered, the neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection obtained by a combination of neurotrophic factors may be less than that of a single neurotrophin.

  • 3.
    Novikova, Liudmila N
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellerth, Jan-Olof
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Differential effects of neurotrophins on neuronal survival and axonal regeneration after spinal cord injury in adult rats.2002In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 452, no 3, p. 255-63Article in journal (Refereed)
    Abstract [en]

    Spinal cord injury (SCI) induces retrograde cell death in descending pathways, which can be prevented by long-term intrathecal infusion of neurotrophins (Novikova et al. [2000] Eur J Neurosci 12:776-780). The present study investigates whether the same treatment also leads to improved regeneration of the injured tracts. After cervical SCI in adult rats, a peripheral nerve graft was attached to the rostral wall of the lesion cavity. The animals were treated by local application into the cavity of Gelfoam soaked in (1) phosphate buffered saline (untreated controls) or (2) a mixture of the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) (local treatment), or by intrathecal infusion of BDNF + NT-3 for (3) 2 weeks (short-term treatment) or (4) 5-8 weeks (long-term treatment). Despite a very strong survival effect, long-term treatment failed to stimulate ingrowth of descending tracts into the nerve graft. In comparison with untreated controls, the latter treatment also caused 35% reduction in axonal sprouting of descending pathways rostral to the lesion site and 72% reduction in the number of spinal cord neurons extending axons into the nerve graft. Local and short-term treatments neither prevented retrograde cell death nor enhanced regeneration of descending tracts, but induced robust regeneration of spinal cord neurons into the nerve graft. These results indicate that the signal pathways promoting neuronal survival and axonal regeneration, respectively, in descending tracts after SCI respond differently to neurotrophic stimuli and that efficient rescue of axotomized tract neurons is not a sufficient prerequisite for regeneration.

  • 4.
    Vedin, Viktoria
    et al.
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Molander, Marie
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Bohm, Staffan
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Regional differences in olfactory epithelial homeostasis in the adult mouse2009In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 513, no 4, p. 375-384Article in journal (Refereed)
    Abstract [en]

    The olfactory sensory neurons in the nasal cavity of the adult mouse are organized into a few regions that differ in their molecular properties, as several classes of genes show regional expression. Most renowned is the fact that expression of each of hundreds of different odorant receptor genes is limited to one such region, or zone, of the olfactory neuroepithelial sheet. Zone differences are in place at birth, as exemplified here by the expression of neuronal progenitor marker Foxg1. We herein describe that an adult pattern showing regional differences in neurogenesis develops during the first few weeks of postnatal life which, e.g., is reflected in the temporal and regional regulation of the neuronal progenitor marker Ascl1. The most dorsomedial zone shows significantly fewer cells in S-phase in the adult but not in newborn mice by two different measures. Moreover, we show that there are regional differences in the relative differentiation, cell survival, and thickness of the olfactory epithelium. These findings are compatible with the view that zones are inherently distinct and that such differences contribute to generate regional differences in cellular homeostasis that in turn may modulate the capacity of a region to adjust to extrinsic influence.

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