Betamethasone 21-phosphate disodium: Glucocorticoid & Neuro Effects

Betamethasone 21-phosphate disodium salt is a synthetic water-soluble glucocorticoid and works as a glucocorticoid receptor agonist. It shows immunosuppressive, antiallergic, antipruritic and anti-inflammatory effects in vivo.

Long-term betamethasone 21-phosphate disodium treatment has distinct effects

Depression and anxiety diseases are considered public health problems and have been widely studied. Stressful events have been implicated in the precipitation or exacerbation of anxiety and depressive disorders; however, the underlying neural mechanisms still remains unclear. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. Several studies have demonstrated that long-term CORT administration induces neurobiological changes, which are thought to underlie depressive symptomatology. Based on this background, we decided to study the effects of Betamethasone 21-phosphate disodium (BTM) in DBA/2 mice on animal behavior and neurogenesis in order to understand whether BTM might have different effects than CORT. Considering the contrasting results obtained in DBA/2 mice, we have followed the same treatment protocol with BTM in CD1 mice with the aim of comparing Betamethasone 21-phosphate disodium effects in two different strains and with previously published data in the latter strain of mice.[1]

Long-term CORT administration in rodents has been previously used as a suitable model of depressive-like behavior. The initial purpose of our experiments was to investigate the effects of Betamethasone 21-phosphate disodium (BTM) chronic treatment in DBA/2 mice on animal behavior and neurogenesis in order to understand whether BTM would exert similar effects to these elicited by CORT administration. However, after initial experiments evidencing significant differences to what was previously reported in literature for CORT, we have also compared and studied BTM effects in a previously studied strain, namely CD1 mice. Betamethasone 21-phosphate disodium is a widely used corticosteroid for the treatment of allergic and chronic inflammatory diseases and its use has been associated with the appearance of central nervous system side effects including depression, increased anxiety and learning and memory impairment similarly to other corticosteroids. Similarly, long-term exposure to glucocorticoids in rodents results in impaired learning and memory, reduced neurogenesis and synaptic plasticity in the hippocampus and increased anxiety and depressive-like symptomatology. Regarding BTM's effects, our results in CD1 mice are in agreement with previous reports for similar long-term CORT treatment. Briefly, Betamethasone 21-phosphate disodium treatment increased body weight gain and anxiety parameters while had no effects on IT in the FST while having pro-depressant effects according to coat state deterioration.

At odds, long-term Betamethasone 21-phosphate disodium administration, in DBA/2 mice, caused a significant reduction in the body weight while it did not modify the anxiety parameters in the OF, EPM and NSF. In addition, in BTM-treated DBA/2 mice in comparison to untreated group, both an increased synaptogenesis and a further increase in neurogenesis, was found. Similarly to CD1 mice, also in DBA/2 mice memory and learning in the MWM were impaired by Betamethasone 21-phosphate disodium treatment, however, in this latter strain, an impairment in locomotor activity in the test was noted. Overall, it is clear that the two strains respond differently to BTM treatment, however, the lack of effects in DBA/2 mice might be linked to their already anxious phenotype even though, in the MWM, similar effects for the two strains were observed and also in this case, DBA/2 mice had poorer performances on basal conditions. The most striking difference is related to the opposite effects on neurogenesis. Our data confirm that long-term exposure to corticosteroids can generate or aggravate psychiatric/neurologic disorders such as depression, anxiety, memory and learning. Our study did not reveal significant differences between CORT and BTM treatment in the same strain of mice (CD1). In contrast, Betamethasone 21-phosphate disodium treatment in mice with an already established anxious phenotype revealed some contrasting results indicating that genetic factors can influence corticosteroids dependent central nervous system effects.

References

[1]Aiello, Rossana et al. “Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.” Behavioural brain research vol. 278 (2015): 155-66. doi:10.1016/j.bbr.2014.09.042

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