Internal coincidence of serotonergic and dopaminergic oscillations modulates photo sexual responses of Japanese quail, <i style="mso-bidi-font-style:normal">Coturnix coturnix japonica</i>

489-495Specific temporal phase relation of neural oscillations appears to be the regulator of gonadal development in many seasonally breeding species. To find out the specific phase angle of two neural oscillations that triggers gonado-inhibitory or gonado-stimulatory response, and to test the internal coincidence model, sexually immature male Japanese quail were administered with the serotonin precursor, 5-hydroxytryptophan and the dopamine precursor, L-dihydroxyphenylalanine at hourly intervals of 6, 7, 8, 9, 10, 11 and 12 h (5 mg/100 g body weight/day for 12 days under continuous condition of light, LL). Thereafter all the groups were shifted to long photoperiod (LD16:8). During post-treatment period, in general, a significant suppression of gonadal activity was seen in the 7 h and 8 h quail and an increase in the 11 h and 12 h quail compared to the control and these effects were maintained until 105 days post treatment when the study was terminated. These findings suggest that, in addition to the effects of photoperiod, the gonadal development of Japanese quail may be also modulated by internal coincidence of serotonergic and dopaminergic oscillations (induced by the administration of their precursor drugs) and the gonadal response varies depending on the time interval between the administrations of two drugs on a circadian basis. These results also demonstrate inversion of gonadal response from 7/8 h (suppressive) to 11/12 h (stimulatory) phase relation of the two oscillations and suggest that similar to photoperiodic time measurement, Japanese quail may also detect changes in the phase angle of circadian oscillations to modulate its gonadal activity

Temporal Phase Relation of Circadian Neural Oscillations Alters RFamide-Related Peptide-3 and Testicular Function in the Mouse

In order to study the effect of the temporal synergism of neural oscillations on reproductive regulation and the response of RFamide-related peptide-3 (RFRP-3; a mammalian ortholog of avian gonadotropin-inhibitory hormone), expression of immunoreactive RFRP-3 in the neurons of the dorsomedial nucleus of the hypothalamus was monitored in sexually immature and mature laboratory mice (study I). In study II, the effects of serotonin and dopamine precursors (5-hydroxytryptophan and L-dihydroxyphenylalanine; injected daily, 8 or 12 h apart, for 13 days in 3-week-old mice) on testicular activity and immunoreactive RFRP-3 neurons were studied until 24 days after treatment. Results indicate high levels of expression of immunoreactive RFRP-3 in the sexually immature and 8-hour mice (simulating gonadal suppression), while a low level was noted in mature and 12-hour mice (simulating gonadal stimulation). These findings not only suggest the modulation of gonadal development in mice (during the course of puberty attainment) by changing the temporal phase relation of serotonergic and dopaminergic oscillations (as in some seasonally breeding species), but also demonstrate an inverse correlation of RFRP-3 neurons and gonadal activity in both control and experimental conditions

Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation - Fig 4

<p><b>(A)</b> Morphological changes of PC-3 cells with and without PNKPi (A12B4C3) treatment after 2Gy and 4Gy of ¹²C beam. The combination treated group showedmorphological changes as compare to only irradiated and control cells. <b>(B)</b>Cellpopulation decreased in combination treatment samples.***p<0.001, significance of difference from control and ^#p<0.05in comparison with the only irradiated group.<b>(C)</b>Cell proliferaton (%) decreased when ¹²C beam is combined with PNKPi. ***p<0.001, significance of difference from control and ^###p<0.001, significance of difference from only irradiated group respectively.</p

FACS analysis showing distribution of cells % (cell cycle arrest at different phases).

<p>G2/M phase arrest was enhanced in PNKPi treated group comapred to control cells. **p<0.01; ***p<0.001, significance of difference compared to control and ^#p<0.05, ^##p<0.01 in comparison with the only irradiated group.</p

Bar graph represents the increase in absorbance (OD) at 405 nm due to the release of <i>p</i>-nitroanilide.

<p>Caspase-3 activity was highly increased in PNKPi treated group compare to only irradiated group.***p<0.001 significance of difference from only irradiated group.</p

Schematic work flow for experiments.

<p>Schematic work flow for experiments.</p

Surviving fraction (SF) graphs of PC-3 cells.

<p>(<b>A)</b>Note a dose dependent SF curve when PC-3 cell were treated with ¹²C beam only. <b>(B)</b> Effect of different concentration of PNKPi A12B4C3 on SF of PC-3 cells note that cells were least toxic till 10μM concentration.<b>(C-F)</b> Effect of different doses of ¹²C beam (<b>―</b>)with different concentration of A12B4C3 (…..) note a decrease in the SF as the concentration of A12B4C3 increases with ¹²C irradiation.</p