Brain-derived neurotrophic factor/TrkB signaling regulates daily astroglial plasticity in the suprachiasmatic nucleus: electron-microscopic evidence in mouse.

Synchronization of circadian rhythms to the 24-h light/dark (L/D) cycle is associated with daily rearrangements of the neuronal-glial network of the suprachiasmatic nucleus of the hypothalamus (SCN), the central master clock orchestrating biological functions in mammals. These anatomical plastic events involve neurons synthesizing vasoactive intestinal peptide (VIP), known as major integrators of photic signals in the retinorecipient region of the SCN. Using an analog-sensitive kinase allele murine model (TrkB(F616A) ), we presently show that the pharmacological blockade of the tropomyosin-related kinase receptor type B (TrkB), the high-affinity receptor of brain-derived neurotrophic factor (BDNF), abolished day/night changes in the dendrite enwrapping of VIP neurons by astrocytic processes (glial coverage), used as an index of SCN plasticity on electron-microscopic sections. Therefore, the BDNF/TrkB signaling pathway exerts a permissive role on the ultrastructural rearrangements that occur in SCN under L/D alternance, an action that could be a critical determinant of the well-established role played by BDNF in the photic regulation of the SCN. In contrast, the extent of glial coverage of non-VIP neighboring dendrites was not different at daytime and nighttime in TrkB(F616A) mice submitted to TrkB inactivation or not receiving any pharmacological treatment. These data not only show that BDNF regulates SCN structural plasticity across the 24-h cycle but also reinforce the view that the daily changes in SCN architecture subserve the light synchronization process.

Intracerebral administration of brain-derived neurotrophic factor (BDNF) reduces severity of cataleptic freezing in mice with genetic predisposition to catalepsy.

Single administration of brain-derived neurotrophic factor (BDNF) into the lateral ventricle of ASC mice (Antidepressant Sensitive Catalepsy), a model of depression-like state, significantly decreased predisposition to cataleptic freezing in these animals. These findings indicate that BDNF can appear as a promising antidepressant of new generation and that ASC mice can be used as an adequate model for investigations of the mechanisms of behavior modification by BDNF.

Activity-dependent dynamics of coexisting brain-derived neurotrophic factor, pro-opiomelanocortin and alpha-melanophore-stimulating hormone in melanotrope cells of Xenopus laevis.

Brain-derived neurotrophic factor (BDNF) is involved as an autocrine factor in the regulation of the secretory activity of the neuroendocrine pituitary melanotrope cells of Xenopus laevis. We studied the subcellular distribution of BDNF in Xenopus melanotropes using a combination of high-pressure freezing, cryosubstitution and immunoelectron microscopy. Presence of BDNF, pro-opiomelanocortin (POMC) and alpha-melanophore-stimulating hormone (alphaMSH) within melanotrope secretory granules was studied by triple-labelling immunoelectron microscopy. In addition, intracellular processing of BDNF was investigated by quantifying the number of immunogold particles in different stages of secretory granule maturation, in animals adapted to black or white background light conditions. The high-pressure freezing technique provides excellent preservation of both cellular ultrastructure and antigenicity. BDNF coexists with POMC and alphaMSH within secretory granules. BDNF-immunoreactivity increases along the secretory granule maturation axis (i.e. from electron-dense, via moderately electron-dense, to electron-lucent secretory granules). Immature, low immunoreactive, electron-dense secretory granules are assumed to contain mainly or even exclusively proBDNF. Strongly immunoreactive electron-lucent secretory granules represent the mature granule stage in which proBDNF has been processed to mature BDNF. Furthermore, in moderately electron-dense secretory granules, immunoreactivity is markedly (+79%) higher in black-adapted than in white-adapted animals, indicating that stimulation of melanotrope cell activity by the black background condition speeds up processing of BDNF from its precursor in this granule stage. It is concluded that, in the Xenopus melanotrope, BDNF biosynthesis and processing occur along the secretory granule maturation axis, together with that of POMC-derived alphaMSH, and that the environmental light condition not only controls the biosynthesis and secretion of BDNF and of POMC end-products, but also regulates the rate of their intragranular processing.