Traumatic stress-induced persistent changes in DNA methylation regulate neuropeptide Y expression in rat jejunum.

BACKGROUND: Stress-induced chronic neuropsychiatric conditions such as anxiety are often co-morbid with gastrointestinal malfunctions. While we find enduring anxiety-like symptoms following minimal traumatic brain injury (MTBI) in rats, gastrointestinal consequences of MTBI remain elusive. METHODS: In this study, we examined the effects of MTBI on a major gut peptide, neuropeptide Y (NPY) and gut motility. DNA methylation was studied as a possible epigenetic mechanism operative in the regulation of NPY expression in the gut. KEY RESULTS: Minimal traumatic brain injury reduced the gut motility 48 hours and 30 days after trauma. The expression of DNA methyltransferase isoforms (DNMT1, DNMT3a, and DNMT3b) was altered in the jejunum 48 hours and 30 days after MTBI. However, the mRNA levels of growth arrest and DNA damage 45 (GADD45) isoforms, GADD45a, and GADD45b, which are believed to be involved in active DNA demethylation, initially decreased at 48 hours but subsequently increased after 30 days of trauma. Similarly, DNA hypomethylation at the NPY promoter region in the jejunum was correlated with the increase in NPY mRNA and protein levels 30 days post-trauma. On the other hand, DNA hypomethylation at 48 hours was associated with a decline in NPY expression. Treatment with 5-azacytidine (5-AzaC), a DNMT inhibitor, retarded DNA methylation and restored the NPY mRNA levels in the jejunum of MTBI-induced rats. CONCLUSIONS & INFERENCES: These results suggest that DNA demethylation could be operative as an epigenetic mechanism in the long-term regulation of NPY gene expression to alter the gut motility during traumatic stress.

Reproduction phase-related expression of beta-endorphin-like immunoreactivity in the nucleus lateralis tuberis of the female Indian major carp Cirrhinus mrigala: correlation with the luteinising hormone cells-ovary axis.

The present study aimed to determine whether beta-endorphin immunoreactivity (bEP-ir) in the neurones of the nucleus lateralis tuberis (NLT) is linked to the seasonal cycle and shows correlation with the number of luteinising hormone (LH) cells in the pituitary gland and ovaries in the teleost, Cirrhinus mrigala. Although LH cells were moderately immunostained during the resting phase (December to January), the morphological profile suggested increased synthetic and secretory activity during the preparatory (February to April) and prespawning (May to June) phases. However, LH immunoreactivity was greatly reduced (P < 0.001) in the spawning (July to August) phase, suggesting massive discharge of the hormone; this pool was partly replenished in the postspawning (September to November) phase. The ovaries grew rapidly in the preparatory and prespawning phases; maximal size was attained during spawning, when ovulation occurred. Thereafter, the ovaries regressed. The NLT of C. mrigala is divisible into the pars lateralis (NLTl) and medialis (NLTm). During the postspawning and resting phases, bEP-ir was readily detectable in the NLTm as well as NLTl neurones. However, a steady reduction in the immunoreactivity was observed in the NLTm neurones during the preparatory through spawning phases (P < 0.001), suggesting a negative correlation with the LH cells-ovary axis. Thus, the inhibitory influence of beta-endorphin on the gonadotrophin-releasing hormone (GnRH)-LH axis appears to be attenuated during the preparatory through spawning phases. This may be necessary for the rapid stimulation of the axis culminating in spawning. Neurones of the NLTl also showed a gradual reduction in bEP-ir during the preparatory and prespawning phases (P < 0.01) and may therefore play a similar role. However, significant augmentation of the immunoreactivity was noticed in these neurones during the spawning phase (P < 0.001), the physiological significance of which is unknown. Although the present study demonstrated a temporal correlation between the beta-endorphin in the NLT, LH cells and the ovary, we suggest that the peptide in the NLTl and NLTm may show functional duality during the spawning phase.