Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain

Abstract

A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic pain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p-chloroamphetamine (PCA). The neurotrophins (5–12 micrograms/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5- HIAA contents and 3H-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA.

Interaction between BDNF and Serotonin: Role in Mood Disorders

“…Treatment of cultured neurons derived from embryonic raphe with BDNF dramatically increases the number of cells that express 5-HT markers and stimulates their morphological complexity (Eaton and Whittemore, 1996;Zhou et al, 2000;Rumajogee et al, 2002;Djalali et al, 2005). Intracerebroventricular infusion of BDNF stimulates sprouting of 5-HT axons, leading to hyperinnervation at the site of injection (Mamounas et al, 1995(Mamounas et al, , 2000.…”

BDNF in schizophrenia, depression and corresponding animal models

“…34 BDNF exerts a potent neurotrophic effect on the 5-HT neurons when infused into midbrain, 35 while infusion of BDNF into forebrain results in a dramatic elevation of 5-HT neuronal fiber density and protection of neurons from neurotoxic damage. 36 In addition, BDNF expression can also be regulated by serotonin. 17,37,38 Finally, BDNF promotes survival of rat embryonic septal cholinergic neurons in vitro and increases the activity of enzymes involved in choline acetyl transferase synthesis and degradation.…”

Parental brain‐derived neurotrophic factor genotype, child prosociality, and their interaction as predictors of parents’ warmth

“…(2016) have shown how the parents’ serotonin transporter genotype moderates the association between child noncompliance and parental negativity. We chose to focus on the brain‐derived neurotrophic factor (BDNF), which has been associated with both the serotonergic (Eaton, Staley, Globus, & Whittemore, 1995; Mamounas, Blue, Siuciak, & Altar, 1995) and dopaminergic systems (Guillin et al., 2001; Küppers & Beyer, 2001). …”