Dehydroepiandrosterone Stimulates Nerve Growth Factor and Brain Derived Neurotrophic Factor in Cortical Neurons

Abstract

Due to the increasing cases of neurodegenerative diseases in recent years, the eventual goal of nerve repair is very important. One approach for achieving a neuronal cell induction is by regenerative pharmacology. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are neurotrophins that play roles in neuronal development, differentiation, and protection. On the other hand, dehydroepiandrosterone (DHEA) is a neurosteroid which has multiple actions in the nervous system. DHEA could be an important agent in regenerative pharmacology for neuronal differentiation during tissue regeneration. In this study, we investigated the possible role of DHEA to modulate NGF and BDNF production. The in vivo level of neurotrophins expression was demonstrated by ELISA in rat harvested brain cortex. Also neurotrophins expression after DHEA treatment was revealed by the increased neurite extension, immunostaining, and BrdU labeling in rats. Anti-NGF and anti-BDNF antibodies were used as suppressive agents on neurogenesis. The results showed that NGF and BDNF are overproduced after DHEA treatment but there is not any overexpression for NT-3 and NT-4. Also DHEA increased neurite extension and neural cell proliferation significantly. Overall, DHEA might induce NGF and BDNF neurotrophins overproduction in cortical neurons which promotes neural cell protection, survival, and proliferation.

Polymorphisms of STS gene and SULT2A1 gene and neurosteroid levels in Han Chinese boys with attention-deficit/hyperactivity disorder: an exploratory investigation

“…Therefore, compatible with our findings, previous data in mice have suggested a link between attention and DHEA(S) levels921222324. The protective effects of DHEA(S) on patients’ neuropsychological function may account for enhancing neuron growth5, regulating GABA A and NMDA activity67, or modulating the complex process of cortical maturation during middle childhood5758. DHEA and DHEA-S may also play independent roles in some aspects of the nervous system.…”

“…Dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S) are important neurosteroid substrates that are critical for various physiological processes and involved in several neuropsychiatric diseases5. DHEA(S) may facilitate neurite extension and neural cell proliferation and is thus important for regulating neurodevelopment67. Furthermore, DHEA(S) exerts stimulatory or antagonistic effects at gamma-aminobutyric acid (GABA A ) receptors and facilitates N-methyl-D-aspartate (NMDA) activity8.…”

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces

“…Explicitly, prior reports demonstrate not only that DHEAS reliably predicts sNGF at rest, during intense stress exposure, and in recovery; but also that DHEAS changes predict sNGF changes across the acute stress trajectory. Considering these findings together with the broader pre-clinical and experimental literature [53], we cautiously suggest that (1) DHEAS and sNGF are inextricably linked at rest and under stress, (2) these analytes respond to stress in similar ways, and (3) their interrelationships are jointly explained by a multifactorial web of genetic, environmental, and molecular mechanisms.…”

“…Because neurotrophins and anabolic sex hormones respond predictably to realistic stress [25,26] and may sustain cell survival during stressful insult [27,28], their response signatures may underlie resilience to stress and trauma. A better understanding of their roles may advance prevention and treatment of traumatic stress and injury [29], degenerative disease management [30], and nerve repair [31]. This may also help to identify the counterbalancing effects of resilience-building interventions in individuals with vulnerable genetic profiles.…”

An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans

“…Additionally, DHEA has neuroprotective effects in autoimmune neurodegenerative processes [56][57][58], brain ischemia [59], and brain trauma [60][61][62]. DHEA and/or DHEAS also demonstrate anti-inflammatory effects [63][64][65] and increase neurogenesis [66][67][68]. Thus, potential analgesic effects of DHEA and/or DHEAS may result, at least in part, from their anti-inflammatory actions.…”