Temporal synergism of neurotransmitters (serotonin and dopamine) affects testicular development in mice
Introduction
In seasonally breeding vertebrates, gonadal development and associated breeding activities are controlled by environmental cues such as photoperiod and temperature. Changes in the daily photoperiod (day length) registered by the organism is the most common trigger of the annual gonadal development and regression, suggesting that the circannual organization receives input from the circadian organization. The photic information is transmitted to the endocrine system via the hypothalamo–hypophyseal–gonadal axis. In mammals, the suprachiasmatic nuclei (SCN) play a central role in the circadian system. Other areas like the pineal gland may also be involved since rhythmicity is not completely eliminated following bilateral lesions of the SCN (Moore-Ede, 1983; Moore et al., 1995). Significant circadian rhythms of hypothalamic serotonin and dopamine concentrations have been observed in the SCN of hamsters, which had a 12- to 16-hr phase relationship in the scotorefractory and a 0- to 4-hr phase relation in the scotosensitive condition (Wilson and Meier, 1987).
The pioneer study by Meier's group on the white-throated sparrow hypothesized that endogenous seasonality, which determines photosensitivity and photorefractoriness, involves the temporal interaction of two circadian neural oscillations (Miller and Meier, 1983a, Miller and Meier, 1983b). The experimental basis of this hypothesis was that hormone activity, e.g. of corticosterone and prolactin, differs as a function of the time of the day and that the phase of these circadian hormonal rhythms changes seasonally. Based on the evidence that hormonal rhythms are the expression of neural rhythms, in later experiments 5-hydroxytryptophan (5-HTP), a rate-limiting precursor substrate for serotonin, was substituted for corticosterone, and L-dihydroxyphenylalanine (l-DOPA), a rate-limiting precursor for dopamine, was substituted for prolactin. In fact, the circadian rhythms of some hormones, such as corticosterone and prolactin, appear to be an important expression of these (serotonergic and dopaminergic) oscillations and by feedback mechanisms hormonal rhythms may not only maintain the neural oscillations but may also entrain each other (Meier et al., 1971).
According to mammalian literature, brain serotonergic activity influences adrenal corticosteroid secretion, and parachlorophenylalanine (PCPA), which blocks the synthesis of serotonin, dampens the plasma corticosteroid rhythm (Scapagnini et al., 1971; Balestrery and Moberg, 1973; Owasoyo and Walker, 1980). Systemic 5-HTP and intraventricular 5-hydroxytryptamine (5-HT, i.e. serotonin) cause a rise in plasma corticosteroid concentration (Popova et al., 1972), which in turn exerts a feedback effect on the synthesis of brain 5-HT (Telegdy and Vermes, 1975; Sze et al., 1976). This effect results from stimulation of brain tryptophan hydroxylase activity which catalyzes the conversion of tryptophan to 5-HT. Thus, circadian variation may affect many systems and oscillations including hormonal and neural systems with different time courses. And circadian variation in different endocrine or neural activities may be correlated with seasonal variation in physiological functions. In this context, Wilson and Meier (1989) reported a resetting of the annual cycle (scotorefractory and scotosensitive conditions) in the Syrian hamster with timed daily injections of 5-HTP and l-DOPA.
This hypothesis was further confirmed by many reports from our laboratory on different species of seasonally breeding birds, namely the red-headed bunting, Emberiza bruniceps (Chaturvedi and Bhatt, 1990), the Japanese quail, Coturnix coturnix japonica (Phillips and Chaturvedi, 1995), the spotted munia, Lonchura punctulata (Prasad and Chaturvedi, 1998), the lal munia, Estrilda amandava (Chaturvedi et al., 1994) and one species of mammal, the Indian palm squirrel, Funambulus pennanti (Chaturvedi and Jaiwal, 1990; Jaiwal and Chaturvedi, 1991; Chaturvedi and Singh, 1992). All these findings suggest that the temporal phase relation of circadian neural oscillations may induce specific reproductive/metabolic conditions in seasonal breeders. A number of studies on Japanese quail (which breeds continuously if maintained under constant day length and shows a seasonal gonadal cycle if maintained under natural day length; Chaturvedi et al., 1993) also indicate a regulatory role of circadian organization (specific phase relation of circadian neural oscillations) in the functional maturation of the neuroendocrine–gonadal axis and puberty attainment (Phillips and Chaturvedi, 1995), during photosexual responses (Chaturvedi et al., 1991) including photorefractoriness (Chaturvedi et al., 2006) and in fertility/egg production (Tiwari and Chaturvedi, 2003). This treatment (5-HTP and l-DOPA given at specific time intervals), in addition to modulating the gonadal activity, is also reported to alter the phase relation of the circadian hypothalamic content of serotonin and dopamine in the quail (8-hr and 12-hr intervals; Kumar et al., 2009). Interestingly, circadian variation in the hypothalamic serotonin and dopamine content also exhibits different phase relations in the breeding and non-breeding quail (Tiwari et al., 2006).
However, it is not known if this mechanism may also be effective in a continuous breeder, especially during maturation of the gonadal axis. Hence, the present study was designed to address the putative regulatory role of circadian oscillations in the reproductive development of laboratory mice. The aim of the study was to investigate if normal gonadal development in pre-puberal mice may be altered as a function of the specific phase relation of neurotransmitter precursors that are reported to regulate seasonal physiological and behavioral changes in relation to reproduction injected at different time intervals.
Section snippets
Animals
Male laboratory mice (Mus musculus) of the Parkes (P) strain were obtained from a colony maintained in our laboratory. The mice were housed under hygienic conditions in a well-ventilated, photoperiodically controlled room (LD 12:12) and were provided with commercial food (Pashu Aahar Kendra, Varanasi, India) and tap water ad libitum. All the experiments were conducted in accordance with institutional practice and within the framework of the revised Animals (Scientific Procedures) Act of 2002 of
Results
At the termination of the study, 8-hr mice had lower body weight, while 12- and 20-hr mice weighed significantly more compared to the control group (Table 1). There was also a decrease in the testicular volume of 8-hr mice but the other experimental groups were not different from controls (Fig. 1A). However, the GSI did not show any variation among the different groups of mice (Fig. 1B). The sperm count was significantly decreased in the 8-hr and increased in the 12-hr mice as compared to the
Discussion
Our results indicate that the daily injections of serotonergic and dopaminergic precursor drugs given in a particular temporal relation altered reproductive development and age-dependent body weight gain in mice. At the age of about 8 weeks (i.e. 58 days), spermatogenesis was arrested in the 8-hr group, accompanied by a low testosterone level and highly reduced sperm counts, motility and viability. In addition to these degenerative changes, abnormality was evident in 45–50% of sperms as
Acknowledgements
This work was supported by funds from the Council of Scientific and Industrial Research (CSIR), New Delhi, India, to C.M.C. (research project 37/1284/07/EMR-II). A Senior Research Fellowship to S.S. from the Indian Council of Medical Research (ICMR) is gratefully acknowledged.
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2016, Physiology and BehaviorCitation Excerpt :Further, 12-h temporal phase relations of neural oscillations alter the photo sexual responses of immature Japanese quail [19] while the 8-h relation of serotonergic and dopaminergic drugs induce reproductive regression in quail under relatively short-day lengths and exhibit scotosensitive responses under short days [20]. Specific phase relations of neural oscillations are also reported to modulate reproduction in mammals whether seasonal (Syrian hamster - [21]; Indian Palm Squirrel - [22] or continuous breeders (laboratory mice) -[23]. Thus, both photoperiod and specific temporal phase relations of neural oscillations appear to be regulators of gonadal development/activity in many avian and mammalian species.
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Interaction of specific temporal phase relations of circadian neural oscillations and long term photoperiodic responses in Japanese quail, Coturnix coturnix japonica
2015, General and Comparative EndocrinologyCitation Excerpt :Further, 12-h temporal phase relations of neural oscillations alter the photo sexual responses of immature Japanese quail (Chaturvedi et al., 1991) while the 8-h relation of serotonergic and dopaminergic drugs induce reproductive regression in quail under relatively short-day lengths (<11 h) and exhibit scotosensitive responses under short days (Bhatt and Chaturvedi, 1992a). Specific phase relations of neural oscillations are also reported to modulate reproduction in mammals whether seasonal (Syrian hamster- Wilson and Meier, 1989; Indian Palm Squirrel- (Chaturvedi and Jaiwal, 1990; Jaiwal and Chaturvedi, 1991; Chaturvedi and Singh, 1992; Singh and Chaturvedi, 1993) or continuous breeders (laboratory mice- Sethi and Chaturvedi, 2009; Sethi et al., 2010). Thus, both photoperiod and specific temporal phase relations of neural oscillations appear to be regulators of gonadal development/activity in many avian and mammalian species.
Age-dependent variation in the RFRP-3 neurons is inversely correlated with gonadal activity of mice
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