Differential expression of calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT) in the axotomized motoneurons of normoxic and hypoxic rats.
We employed a double injury model (axotomy along with hypoxia) to determine how nerve injury and hypoxic insult would affect the expression of calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT) in the hypoglossal nucleus (HN) and nucleus ambiguus (NA). Adult rats were subjected to unilateral vagus and hypoglossal nerve transection, following which half of the animals were kept in an altitude chamber (PO2=380 Torr). The immunoexpression of CGRP and ChAT (CGRP-IR/ChAT-IR) were examined by quantitative immunohistochemistry at 3, 7, 14, 30 and 60 days post-axotomy. The results revealed that CGRP-IR in the HN was increased at 3 days but decreased to basal levels at 7 days following nerve injury. The decline was followed by a second rise in CGRP-IR at 30 days post-axotomy, followed again by a return to basal levels at 60 days. In the NA, CGRP-IR was up-regulated at 3 days and remained increased for up to 60 days after nerve injury. Animals treated with a double injury showed a greater CGRP-IR than normoxic group in both nuclei at all post-axtomized periods. In contrast to CGRP, ChAT-IR was markedly reduced in the HN and NA at 3 days reaching its nadir at 14 days following nerve injury. Hypoxic animals showed a stronger reduction of ChAT-IR in both nuclei at all post-axtomized periods. Results of cell counting showed that neuronal loss was somewhat obvious in hypoxic HN than that of normoxic ones. The present results suggest that up-regulation of CGRP-IR may exert its trophic effects while down-regulation of ChAT-IR may correlate with the poor neurotransmission within the injured neurons. It is speculated that the enhanced expression of CGRP-IR and the pronounced reduction of ChAT-IR in hypoxic rats may result from a drastic shift of intracellular metabolic pathways, which in turn could lead to more metabolic loading to the severely damaged neurons following the double insult.
Chang
Hung-Ming
HM
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
Wei
I-Hua
IH
Tseng
Chi-Yu
CY
Lue
June-Horng
JH
Wen
Chen-Yuan
CY
Shieh
Jeng-Yung
JY
D000818:Animals; D019771:Axotomy; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015687:Cell Hypoxia; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009046:Motor Neurons / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D002795:Choline O-Acetyltransferase; D015740:Calcitonin Gene-Related Peptide