Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment.

Abstract

The effect of intracerebroventricular iqjection of the mitosis inhibitor colchicine on expression of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 was studied in the rat brain with in situ hybridization. Colchicine up-regulates mRNA for NGF and BDNF in many of the neuronal systems normally expressing these factors. In addition, after colchicine treatment NGF and BDNF mRNAs were localized in several brain areas where they normally cannot be detected. Thus, NGF mRNA was present, for example, in many motor nuclei and in the basal forebrain, and BDNF mRNA was seen in many nuclei in the brain stem and in catecholamine neurons, including dopame neurons in the substantia nigra. The latter neurons have recently been shown to be sensitive to BDNF, and the present results show that these neurons can produce this factor themselves. A decrease in mRNA for BDNF and neurotrophin 3 was seen only in the granular-cell layer of the hippocampal formation. A strong hybridization sgnal for BDNF and neurotrophin 3 mRNA was also observed over several myelinated tracts in treated rats, supporting the hypothesis that glial cells as well as neurons can produce these trophic factors.The antimitotic agent colchicine is known to inhibit axonal transport of neuroactive-compounds (1, 2) and to cause accumulation of transmitter-storage vesicles in cell somata (3). Subsequently colchicine has frequently been used in immunohistochemical studies to increase levels of transmitters, peptides, and related substances in cell bodies (4, 5). Colchicine arrests axonal transport due to microtubule disruption (6). However, it has been assumed that protein/ peptide synthesis remains unaffected, leading to accumulation of various compounds in the cell bodies.More recently colchicine has been shown to have a more complex action on neurons. For example, colchicine increases c-Fos levels in many brain areas (7) and causes changes in mRNA levels for a number of peptides, enzymes, and other substances (8). For instance, in the cholinergic basal forebrain system mRNA levels for choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) are lowered, whereas mRNA levels for the peptide galanin are dramatically increased in this and many other systems (8).A similar up-regulation of galanin mRNA levels in basal forebrain neurons occurs after an electrolytic lesion of the hippocampus (9). In other systems it has been proposed that proteins up-regulated after lesions may be needed for restitution and survival and that transmitter-related compounds may be down-regulated (10). For example, the low-affinity 75-kDa nerve growth factor (NGF) receptor is up-regulated in motoneurons after axotomy (11) and after intracerebroventricular injection of colchicine (12).During the last years much interest has been focused on NGF (13), the first member of a family of structurally related neurotrophic factors including brain-derived neurotrophic factor (BDNF) (14, 15), neurotrophin 3 (NT3; also called hippo...

Truncated N-terminal huntingtin fragment with expanded-polyglutamine (htt552-100Q) suppresses brain-derived neurotrophic factor transcription in astrocytes

“…Several studies reported that mhtt decreased the expression of an astroglial glutamate transporter. The consequence of lower astrocytic glutamate uptake might accelerate excitotoxicity and thus contribute to the neuronal damage in HD [48][49][50][51][52]. In the present study, we demonstrated a reduction of BDNF transcription in astrocytes by mutant htt552, suggesting a novel aspect of an astrocytic defect that might cause neuronal dysfunctions in HD.…”

Long Term Effects of Toki-shakuyaku-san on Brain Dopamine and Nerve Growth Factor in Olfactory-Bulb-Lesioned Mice

“…The NGF contents in olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks, but the value returned to normal level within 3 weeks. It has been reported that activated in vivo brain astrocytes may synthesize and secrete NGF-like molecules, when the brain is damaged (25,26). Thus it has been suggested that TSS may exert its action by repairing a neurons injured by zinc sulfate.…”

Peptide Expression in GABAergic Neurons in Rat Suprachiasmatic Nucleus in Comparison with Other Forebrain Structures: A Double Labeling In Situ Hybridization Study

“…Because the bulk of mRNA is confined to the cell body and not to the processes for both GAD (Wuenschell et al 1986) and peptides, this method does not require pretreatment with axonal flow-disrupting drugs such as colchicine (Dahlström, 1971), by which drug-induced phenotypic expression in normally nonexpressing neurons was recently reported (Ceccatelli et al 1991;Kiyama and Emson 1991). However, the co-expression of mRNA does not necessarily indicate co-expression at the protein level.…”