Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo

Abstract

Brain-derived neurotrophic factor (BDNF) has been extensively studied in the central nervous system as a survival and differentiation factor and in plasticity processes. In vitro, BDNF has been shown to stimulate cellular differentiation and neurohormones synthesis and release. We demonstrated that BDNF is a potent and specific stimulatory agent of somatostatin (SRIH) synthesis in primary cultures of hypothalamic neurons. However, less information is available about its function on SRIH neurons in vivo. In the present study, we examined the effect of in vivo intracerebroventricular BDNF administration in adult non-anesthetized male rats. Two distinct experimental approaches were used: acute intracerebroventricular injection and long-term (14 days) continuous infusion (Alzet micro-pumps). We demonstrate that single intracerebroventricular BDNF injections (5 µg/rat) induce an early (60 and 180 min) decrease in the SRIH mRNA signal in the hypothalamic periventricular nucleus (PeVN) accompanied by a decrease of the hypothalamic SRIH content. 48 h after the acute injection, SRIH mRNA levels and peptide content strongly and significantly increased. After continuous intracerebroventricular BDNF administration (12 µg/day for 14 days), a significant increase in the SRIH hypothalamic content was observed. Nevertheless, the increase in peptide content was not correlated with a similar increase in the PeVN messenger level. These findings show the involvement of BDNF in the in vivo regulation of somatostatinergic neurons in adult rats, which clearly differs according to the BDNF administration mode.

Brain-Derived Neurotrophic Factor Signaling Does Not Stimulate Subventricular Zone Neurogenesis in Adult Mice and Rats

“…Based on a rat CSF volume of 250 μl and a turnover rate of 2 hours (Bass and Lundborg, 1973), the CSF should contain approximately 4 μg/ml exogenous BDNF in our pump experiments, whereas Benraiss et al (2001) report 2 ng/ml BDNF in the CSF. However, we used the same BDNF doses as Zigova et al (1998) and several other laboratories have reported biological effects when infusing BDNF at similar doses (Siuciak et al, 1996; Scharfman et al, 2005; Givalois et al, 2006). The weight reduction observed in BDNF-infused animals indicates that this neurotrophin elicited biological effects in our experiments as well.…”

Brain-derived neurotrophic factor (BDNF) affects somatotrophic axis activity in sheep

“…In contrast, the ICV-injected BDNF affected SRIF neuron activity in studies conducted on male rats. In situ hybridisation and RIA assays revealed that after BDNF treatment, the positive cells expressing SRIF mRNA in the PVN and SRIF hypothalamic content decreased (Givalois et al, 2006). The above information comes from studies performed on rodents -nocturnal, monogastric animals with different eating behaviour than ruminants.…”

“…The animals were randomly divided into three experimental groups: control group receiving an ICV infusion of Ringer-Locke solution (artificial cerebrospinal fluid; 480 µl per day; n = 8), BDNF10 group receiving an ICV infusion of BDNF (Santa Cruz Biotechnology, Inc., Dallas, TX, USA) at a dose of 10 μg per day (n = 8) and BDNF60 group receiving BDNF at a dose of 60 μg per day (n = 8); BDNF in both groups was diluted in 480 µl of Ringer-Locke solution; in all three groups an infusion rate was 120 µl/h. The doses of BDNF used in this experiment were chosen based on information from the literature (Barde et al, 1982;Givalois et al, 2006;Cordeira et al, 2010) as well as our previous experience in neuroendocrine research (Przybył et al, 2020).…”

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

“…SST expression and physiological functions in central and peripheral target are modulated by several factors, among them BDNF, a neurotrophic factor, affects its regulation [223,224]. However, the underlying molecular mechanisms describing the role of BDNF in SST mediated food-seeking behaviour and appetite are not well described.…”