Showing papers by "Dan Lindholm published in 1998"
TL;DR: The results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6‐OHDA induced neurotoxicity.
Abstract: The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity. J. Neurosci. Res. 54:698–706, 1998. © 1998 Wiley-Liss, Inc.
97 citations
TL;DR: Increase in the BDNF mRNA levels by kainic acid was not blocked by the protein synthesis inhibitor cycloheximide demonstrating that BDNF is regulated as an immediate early gene in hippocampal neurons.
Abstract: Neuronal activity increases synthesis of brain-derived neurotrophic factor (BDNF) mRNA in vivo and in vitro. We have investigated the pathways through which neuronal activity stimulated by kainic acid regulates BDNF mRNA levels in cultured hippocampal neurons and transgenic mice. Kainic acid induced the transcription of BDNF mRNA without influencing the mRNA stability. Interestingly, the half-life of the 4.2 kb BDNF transcript was much shorter than that of the 1.6 kb transcript (23 +/- 4 min. vs. 132 +/- 30 min). Increase in the BDNF mRNA levels by kainic acid was not blocked by the protein synthesis inhibitor cycloheximide demonstrating that BDNF is regulated as an immediate early gene in hippocampal neurons. Although calmodulin antagonists are known to abolish the effect of kainic acid on BDNF mRNA, this effect was very similar in Ca(+2)-calmodulin-dependent protein kinase II alpha knock-out mice and in wild-type mice. Surprisingly, even high doses of kainic acid failed to increase nerve growth factor (NGF) mRNA in mouse hippocampus although elevation in rat brain has been consistently observed.
81 citations
TL;DR: The present results show that PACAP acts as a trophic factor for DRG neurons and that it is able to modulate the expression of another neuropeptide in the ganglia and suggests thatPACAP acts in a autocrine/paracrine manner possibly in conjunction with other neurotrophic factors such as nerve growth factor.
Abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a recently discovered neuropeptide which is present both in the central and peripheral nervous system of adult rats. Here we show that PACAP is also expressed by dorsal root ganglion sensory neurons of embryonic and newborn rats. To characterize the effects of PACAP on dorsal root ganglion (DRG) neurons, dissociated cultures were established and incubated in the absence or presence of this neuropeptide. The results show that PACAP increases the survival of cultured DRG neurons, and the effect was comparable to that of nerve growth factor (NGF). In DRG explants, PACAP induces the immunoreactivity for the neuropeptide calcitonin gene-related peptide (CGRP). PACAP also promoted the outgrowth of neurites in the DRG cultures. The present results show that PACAP acts as a trophic factor for DRG neurons and that it is able to modulate the expression of another neuropeptide in the ganglia. The presence of PACAP in normal DRG and after nerve lesions suggests that PACAP acts in a autocrine/paracrine manner possibly in conjunction with other neurotrophic factors such as nerve growth factor. J. Neurosci. Res. 51:243-256, 1998. © 1998 Wiley-Liss, Inc.
69 citations
TL;DR: Experimental results that indicate the presence of PACAP and its receptor in the developing nervous system, together with the observed neuropeptide activity on various populations of neurons, support the view that PACAP exhibits important neurotrophic activities comparable to those of the classical neurotrophic factors.
Abstract: To function as a trophic factor PACAP and PACAP-R must be expressed in the nervous system during early development. We report here on the distribution of PACAP mRNA in the developing nervous system of the rat and compare its expression with that of PACAP-R. We discuss primary neuron culture experiments that study the neurotrophic activity of PACAP. Experimental results that indicate the presence of PACAP and its receptor in the developing nervous system, together with the observed neuropeptide activity on various populations of neurons, support the view that PACAP exhibits important neurotrophic activities comparable to those of the classical neurotrophic factors.
57 citations
TL;DR: The present results show that BDNF can be detected in human CSF and that the levels increase following hypoxic-ischemic brain injury, as suggested by animal studies, which might counteract neuronal damage observed in patients following asphyxia.
50 citations
TL;DR: The data suggest that NGF, which is expressed at increased levels in the brain and spinal cord after lesions, may be involved in scar formation in the injured CNS.
Abstract: Nerve growth factor (NGF) induces the differentiation and supports the survival of subpopulations of neurons in the PNS and CNS. Here we report that meningeal cells in the pia mater express immunoreactivity and mRNA for both known NGF receptors, the low-affinity receptor p75 and the tyrosine kinase receptor trkA. NGF induces rapid tyrosine phosphorylation of trkA in meningeal cells in vitro. NGF does not stimulate proliferation of primary meningeal cells but induces process outgrowth. p75- and trkA-immunoreactive meningeal cells with long processes, resembling NGF-treated cells in vitro, are abundant in the scar tissue that forms at spinal cord lesions in rat and cat. These data suggest that NGF, which is expressed at increased levels in the brain and spinal cord after lesions, may be involved in scar formation in the injured CNS.
41 citations
TL;DR: The normal serum levels of nerve growth factor and brain-derived neurotrophic factor together and previously reported low levels of the factor in cerebrospinal fluid indicate that the latter may reflect low levels in the central nervous system.
Abstract: Rett syndrome is now considered to be a neurodevelopmental disease. Its cause is unknown, but it has been suggested that neuronal growth factors and neurotransmitters play important roles. We measured levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid, and nerve growth factor and brain-derived neurotrophic factor in serum in child and adolescent patients with Rett syndrome. Levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in cerebrospinal fluid were below the limit of sensitivity of the methods used. Serum levels of nerve growth factor and brain-derived neurotrophic factor did not differ from control values. In Rett syndrome, the normal serum levels of nerve growth factor together and previously reported low levels of the factor in cerebrospinal fluid indicate that the latter may reflect low levels of nerve growth factor in the central nervous system.
37 citations
Journal Article•
2 citations