Functional nerve growth factor and trkA autocrine/paracrine circuits in adult rat cortex are revealed by episodic ethanol exposure and withdrawal.
The hypothesis tested is that cortical neurotrophins communicate through an inducible autocrine/paracrine mechanism. As ethanol (Et) can induce cortical nerve growth factor (NGF) expression, adult rats were challenged with Et on three consecutive days per week for 6 weeks. The focus of the study was layer V, the chief repository of receptor-expressing neuronal cell bodies. Brains were collected immediately after the sixth Et exposure or 72 h later [i.e., following withdrawal (WD)]. Double-label in situ hybridization-immunohistochemistry studies showed that many neuronal somata co-expressed NGF mRNA with NGF, trkA, or phosphorylated trk (p-trk), essential components of an inducible autocrine system. The frequencies of co-labeling were affected by neither Et nor WD. On the contrary, Et increased the number of NGF mRNA-expressing neurons and the amount of NGF mRNA expressed per cell. Et also increased total cortical concentration of NGF protein, the number of layer V neurons expressing trkA transcript, the amount of trkA mRNA expressed per neuron, and trkA phosphorylation. Following WD, the frequency of NGF-mRNA-expressing cells increased, although transcript and protein content fell. WD induced an increase in trkA mRNA and protein expression, however, p-trk expression was unaffected. Thus, Et treatment reveals that layer V has inducible autocrine/paracrine and anterograde neurotrophin systems. WD unveils the dynamism and recruitability of these systems.
Bruns
Marla B
MB
Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, New York 13210, USA.
Miller
Michael W
MW
D000818:Animals; D019898:Autocrine Communication; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D019899:Paracrine Communication; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D020917:Receptor, trkA / Q000096:biosynthesis / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D012333:RNA, Messenger; D000431:Ethanol; D020932:Nerve Growth Factor; D020917:Receptor, trkA