Endogenous Truncated TrkB.T1 Receptor Regulates Neuronal Complexity and TrkB Kinase Receptor FunctionIn Vivo

Abstract

Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (Trk-B.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific physiological functions and its effect on endogenous TrkB kinase signaling in vivo. We found that TrkB.T1-deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and long-term potentiation. In vivo reduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our results suggest that, at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.

Structure of the Main Olfactory Bulb and Immunolocalisation of Brain-Derived Neurotrophic Factor in the Olfactory Layers of the African Grasscutter (Thryonomys swinderianus - Temminck, 1827)

“…The immunomarker, brain-derived neurotrophic factor was adopted for the present study due to its functional significance in the control of neurogenesis, dendritic growth and synaptic plasticity (Carter et al, 2002;Carim-Todd et al, 2009). The result of the present study revealed a wide-spread localisation of brain-derived neurotrophic factor protein in the olfactory bulb of the African grasscutter at different postnatal periods, and the protein was confined to some specific neurones.…”

Brain-Derived Neurotrophic Factor Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia

“…We found that BDNF induced a sustained increase in TrkB-T1 receptors are predominantly expressed in rat astrocytes (33), while the expression of TrkB-FL receptors is up-regulated after brain injury (55). Although the physiological significance of truncated TrkB receptors is still unknown (38,56), several studies support the importance of TrkB-T1 receptors in the CNS. In cultured rat astrocytes, TrkB-T1 receptors mediate the BDNF-induced elevation of [Ca 2ϩ ]i (33) and are involved in their morphological changes (45).…”

“…In cultured rat astrocytes, TrkB-T1 receptors mediate the BDNF-induced elevation of [Ca 2ϩ ]i (33) and are involved in their morphological changes (45). Carim-Todd et al (56) have recently reported that TrkB-T1-deficient mice develop normally but have increased anxiety-like behavior, accompanied by morphological abnormalities in the dendrites of neurons in the basolateral amygdala. In the present study, we demonstrated that TrkB-T1 receptors were highly expressed in rodent microglial cells (Fig.…”

Prenatal stress decreasesBdnfexpression and increases methylation ofBdnfexon IV in rats

“…Mice that are deficient in TrkB, the Bdnf receptor, show morphological alterations in the amygdala and increased anxiety-like behavior. 30 Additionally, Bdnf was shown to be critical for fluoxetine induced fear extinction. 31 Finally, in human carriers of the Bdnf Val66Met polymorphism, which is associated with depression and anxiety, show reductions in amygdala volume.…”