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To cope with variations in the environment, most mammalian species exhibit seasonal cycles in physiology and behaviour. Seasonal plasticity during the lifetime contributes to seasonal physiology. Over the years, our ideas regarding adult brain plasticity and, more specifically, hypothalamic plasticity have greatly evolved. Along with the two main neurogenic regions, namely the hippocampal subgranular and lateral ventricle subventricular zones, the hypothalamus, which is the central homeostatic regulator of numerous physiological functions that comprise sexual behaviours, feeding and metabolism, also hosts neurogenic niches. Both endogenous and exogenous factors, including the photoperiod, modulate the hypothalamic neurogenic capacities. The present review describes the effects of season on adult morphological plasticity and neurogenesis in seasonal species, for which the photoperiod is a master environmental cue for the successful programming of seasonal functions. In addition, the potential functional significance of adult neurogenesis in the mediation of the seasonal control of reproduction and feeding is discussed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

GPR50, formerly known as melatonin-related receptor, is one of three subtypes of the melatonin receptor subfamily, together with the MT(1) and MT(2) receptors. By contrast to these two high-affinity receptor subtypes and despite its high identity with the melatonin receptor family, GPR50 does not bind melatonin or any other known ligand. Specific and reliable immunological tools are therefore needed to be able to elucidate the physiological functions of this orphan receptor that are still largely unknown. We have generated and validated a new specific GPR50 antibody against the ovine GPR50 and used it to analyse the neuroanatomical distribution of the GPR50 in sheep, rat and mouse whole brain. We demonstrated that GPR50-positive cells are widely distributed in various regions, including the hypothalamus and the pars tuberalis of the pituitary, in all the three species studied. GPR50 expressing cells are abundant in the dorsomedial nucleus of the hypothalamus, the periventricular nucleus and the median eminence. In rodents, immunohistochemical studies revealed a broader distribution pattern for the GPR50 protein. GPR50 immunoreactivity is found in the medial preoptic area (MPA), the lateral septum, the lateral hypothalamic area, the bed nucleus of the stria terminalis, the vascular organ of the laminae terminalis and several regions of the amygdala, including the medial nuclei of amygdala. Additionally, in the rat brain, GPR50 protein was localised in the CA1 pyramidal cell layer of the dorsal hippocampus. In mice, moderate to high numbers of GPR50-positive cells were also found in the subfornical organ. Taken together, these results provide an enlarged distribution of GPR50 protein, give further insight into the organisation of the melatoninergic system, and may lay the framework for future studies on the role of the GPR50 in the brain., (© 2012 The Authors. Journal of Neuroendocrinology © 2012 Blackwell Publishing Ltd.)

In seasonal breeding species, the gene encoding for the melatonin MT(1) receptor (oMT(1)) is highly polymorphic and numerous data have reported the existence of an association between an allele of the receptor and a marked expression of the seasonality of reproduction in ewes. This allele called "m" (previously named "-" allele) carries a mutation leading to the absence of a MnlI restriction site as opposed to the "M" allele (previously named "+" allele) carrying the MnlI restriction site (previously "+" allele). This allows the determination of the three genotypes "M/M" (+/+), "M/m" (+/-) and "m/m" (-/-). This mutation is conservative and could therefore not be causal. However, it is associated with another mutation introducing the change of a valine to an isoleucine in the fifth transmembrane domain of the receptor. Homozygous "M/M" and "m/m" animals consequently express structurally different receptors respectively named oMT(1) Val(220) and oMT(1) Ile(220). The objective of this study was to test whether these polymorphic variants are functionally different. To achieve this goal, we characterized the binding properties and the transduction pathways associated with both variants of the receptors. Using a pharmacological approach, no variation in binding parameters between the two receptors when transiently expressed in COS-7. In stably transfected HEK293 cells, significant differences were detected in the inhibition of cAMP production whereas receptors internalization processes were not different. In conclusion, the possibility that subtle alterations induced by the non conservative mutation in "m/m" animals might modify the perception of the melatoninergic signal is discussed in the context of melatonin action., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Goats and sheep generally express seasonal variations in their sexual behaviour, spermatogenic activity (from moderate decrease to very low sperm production), gamete quality (variations in fertilization rates and embryo survival), ovulation frequency (presence or absence of ovulation), and ovulation rate (number of eggs shed per ovulation period). This induces seasonal availability of derived, fresh animal products (meat, milk and cheese) because of a more or less marked seasonal distribution of births. A complex combination of an endogenous circannual rhythm driven and synchronized by light and melatonin, which controls the pulsatile activity of GnRH neurons in the preoptic-mediobasal hypothalamus, is responsible for these changes. Dramatic and long-term neuroendocrine changes, involving different neuromediator systems and neuronal plasticity, have been shown to play a role in these processes. A strong variability between breeds exists in both species regarding the dates of onset and end of the breeding season, with a gradient of seasonality from southern to northern latitudes. Within a breed, seasonal traits are heritable; thus, genetic selection could be one way to decrease seasonality in sheep and goats in the future., (© 2010 Blackwell Verlag GmbH.)

The gene encoding the MT1 melatonin receptor in sheep has a restriction fragment length polymorphism (RFLP) site to the MnlI enzyme whose incidence is associated to the expression of seasonality in several breeds. The aim of this study was to examine the relationship between this genetic marker and the physiological effects of MT1 receptor gene polymorphism on several seasonal functions in Ile-de-France ewes. The study was performed using 12 pairs of half-sib adult Ile-de-France ewes. Within each pair, ewes were selected on the basis of their genotype at the MnlI RFLP site: group +/+ and -/- (presence and absence of MnlI restriction site, respectively). No difference in the dates of the beginning, the end or the length of the breeding season was observed between groups during the two-year study. The seasonal changes in prolactin secretion were not different between groups. Similarly, wool growth rate and primary follicle activity, measured for one year, varied with the time of the year in the same way in the two groups. Our study therefore failed to show any relationship between MT1 polymorphism and reproductive seasonality in Ile-de-France ewes. This suggests that the influence of this polymorphism on the regulation of seasonal function is dependent upon the breed and/or environmental conditions. The MT1 polymorphism can explain only a small part of the genetic variability of seasonal functions and the implication of other genes must be investigated.

The mechanisms by which melatonin controls seasonal reproduction are poorly understood. The use of a large animal model, namely the sheep, has allowed progress in the understanding of these mechanisms, and is the subject of this review. Firstly, the contribution made by large animal models to demonstrating that melatonin acts in the hypothalamus and the identification of this hypothalamic target is reviewed. Secondly, the way in which large animal models have facilitated the demonstration of a specific mechanism of release of melatonin in the cerebrospinal fluid and, thus, raised the question of the route used by melatonin to reach its central targets is discussed. Finally, the human and agricultural relevance of the data presented is considered.

Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d’Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype −/− at a MnlI restriction site (allele − for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/− and −/−, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and −/−) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study. [ABSTRACT FROM AUTHOR]

Sheep in temperate latitudes are seasonal breeders. Of the different seasonal cues, photoperiod is the most reliable parameter and is used by animals as an indication of the time of the year to synchronize endogenous annual rhythms of reproduction and physiology. The photoperiodic information is transduced into neuroendocrine changes through variations in melatonin secretion from the pineal gland. Melatonin triggers variations in the secretion of luteinizing hormone-releasing hormone, luteinizing hormone and follicle stimulating hormone (LHRH/LH/FSH) responsible for seasonal changes in reproductive activity. In female sheep, the seasonal changes in the hormonal LH pattern mainly reflect an increase in the negative feedback exerted by estradiol under long days on the frequency of pulsatile LH secretion. The resulting seasonal inhibition of LH secretion involves the activation of monoaminergic and especially dopaminergic systems by estradiol. Other types of physiological regulation subject to seasonal changes such as voluntary food intake (VFI), fat metabolism, body mass and pelage growth also occur in sheep, goats or related wild species. Several neuroendocrine intermediates seem to be shared by these different systems and may participate in their synchronization, providing the advantage that this helps mammalian species to adapt to their environment. [Copyright &y& Elsevier]

• Oxytocin regulates female adult neurogenesis in a region specific manner. • Oxytocin decreases the density of neuroblasts in the olfactory bulb. • Oxytocin increases the density of neuroblasts in the hypothalamic niche. New neurons are continuously added in the dentate gyrus of the hippocampus, the olfactory bulb and the hypothalamus of mammalian brain. In sheep, while the control of adult neurogenesis by the social environment or the photoperiod has been the subject of several studies, its regulation by intrinsic factors, like hormones or neurotransmitters is less documented. We addressed this question by investigating the effects of central oxytocin administration on hippocampal, olfactory and hypothalamic neurogenesis. Endogenous markers, Ki67, Sox2 and DCX were used to assess cell proliferation, progenitor cells density and cell survival respectively in non-gestant ewes receiving a steroid treatment followed by intracerebroventricular injections of either oxytocin or saline. The results showed that oxytocin treatment significantly decreases the density of neuroblasts in the olfactory bulb, increases the density of neuroblasts in the ventromedian nucleus of the hypothalamus while no change is observed in both ventral and dorsal dentate gyrus. In addition, no change in the density of progenitor cells is found in the three neurogenic niches. These findings show for the first time that in females, oxytocin can regulate adult neurogenesis by acting on neuroblasts but not on progenitor cells and that this regulation is region specific. [ABSTRACT FROM AUTHOR]