Distribution of GAP‐43 mRNA in the adult rat brain

Abstract

Regional distribution of gene expression of the axonal growth-associated protein, GAP-43, was studied in adult rat brains by in situ hybridization autoradiography to determine the features of mature neuronal populations that synthesize GAP-43 protein. Such synthesis appears to correlate with axonal growth during maturation and regrowth after axotomy. In most adult neurons, the sharp decline in GAP-43 gene expression implies a reduced capacity for axonal growth. Neurons capable of extending axonal knobs in the absence of injury may indicate a "plasticity" underlying dynamic processes of interaction between neurons and their synaptic targets. Antisense and sense (control) riboprobes were used on serial sections in the three principal axes, and the magnitude of hybridization signal was examined to determine regional patterns. GAP-43 mRNA levels are pronounced in diverse neuronal groups including the locus coeruleus, raphé nn., dopaminergic nigral and ventral tegmental nn., mitral cells, hippocampal CA3, inferior olivary n., vagal motor n. and other parasympathetic preganglionic neurons, select thalamic midline and intralaminar nn., several specific nn. of the hypothalamus and basal forebrain, the granular layer of cerebellar cortex, the infragranular neocortex, and the granular olfactory paleocortex; there is a substantial range in the magnitude of expression. Regions revealing minimal signal include most thalamic sensory relay nuclei, the granule neurons of the olfactory bulb and dentate gyrus, and the caudate and putamen. Possible concomitants of GAP-43 expression include regulation of ion flux and neurotransmitter release. Those neurons with long, extensively dispersed and numerous synaptic connections display the strongest signals and may possess the greatest propensity for continuous growth and turnover of their axon terminals, in contrast to short-axon and specific projection neurons exhibiting minimal levels. These data may enable inferring which populations display normal or experimentally induced axonal growth.

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

“…In an early study in the adult rat brain, GAP-43 mRNA was detected at pronounced levels in the hippocampus and particularly the CA3 region, the granular layer of the cerebellar cortex, locus coeruleus, mitral cells, the vagal motor nucleus and other parasympathetic preganglionic neurons, inferior olivary nucleus, raphe nuclei, certain thalamic midline and intralaminar nuclei, dopaminergic nigral and ventral tegmental nuclei, the granular olfactory paleocortex, the infragranular neocortex, and several nuclei of the hypothalamus and basal forebrain [48]. Many of the neurons showing substantial levels of GAP-43 mRNA had both long axonal paths and extensive arborization of terminals [48]. The hippocampal CA3 pyramidal cells, for example, were seen to have a highly dispersed axonal territory [48].…”

“…Many of the neurons showing substantial levels of GAP-43 mRNA had both long axonal paths and extensive arborization of terminals [48]. The hippocampal CA3 pyramidal cells, for example, were seen to have a highly dispersed axonal territory [48]. An increase in the level of GAP-43 has been found in the visual association and frontal cortices of schizophrenic individuals [75].…”

“…Thus, desipramine may increase the level of norepinephrine not only by inhibiting reuptake but also by increasing the level of GAP-43-mediated norepinephrine release. The hippocampus receives noradrenergic innervation soley from the locus coeruleus, which contains GAP-43 mRNA in the adult [48]. When status epilepticus was induced in mice following treatment with pilocarpine, the level of GAP-43 was shown to decrease in the inner molecular layer of the dentate gyrus [12].…”

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

“…Uninjured Purkinje cells do not show B-50/GAP-43 expression either during development (Oestreicher and Gispen, 1986;Console-Bram et al, 1996) or in adulthood (Oestreicher and Gispen, 1986;Meberg and Routtenberg, 1991;Kruger et al, 1993;Baürle et al, 1994;Console-Bram et al, 1996). However, it is not known whether B-50/GAP-43 can be upregulated in adult Purkinje cells after axon injury or transplantation of growthpromoting tissues.…”

Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides

“…[17][18][19] We also found a high expression of GAP-43 mRNA in the limbic system of the adult rat including the amygdala and neo-cortex. 20 Similarly, in human brain, the transcript of GAP-43 is enriched in the cortex and limbic system. 21 Recently, increased levels of GAP-43 were found in visual, associative and frontal cortices of schizophrenic brain.…”