Olfactory sensory deprivation increases the number of proBDNF-immunoreactive mitral cells in the olfactory bulb of mice

Abstract

In the olfactory bulb, apoptotic cell-death induced by sensory deprivation is restricted to interneurons in the glomerular and granule cell layers, and to a lesser extent in the external plexiform layer, whereas mitral cells do not typically undergo apoptosis. With the goal to understand whether brain-derived neurotrophic factor (BDNF) mediates mitral cell survival, we performed unilateral-naris occlusion on mice at postnatal day one (P1) and examined the subsequent BDNF immunoreactive (BDNF-ir) profile of the olfactory bulb at P20, P30, and P40. Ipsilateral to the naris occlusion, there was a significant increase in the number of BDNF-ir mitral cells per unit area that was independent of the duration of the sensory deprivation induced by occlusion. The number of BDNF-ir juxtaglomerular cells per unit area, however, was clearly diminished. Western blot analysis revealed the presence of primarily pro-BDNF in the olfactory bulb. These data provide evidence for a neurotrophic role of proBDNF in the olfactory system of mice and suggest that proBDNF may act to protect mitral cells from the effects of apoptotic changes induced by odor sensory deprivation.

Mature and Precursor Brain-Derived Neurotrophic Factor Have Individual Roles in the Mouse Olfactory Bulb

“…At the same time, mitral cells appeared to gain BDNF immunoreactivity. We also found that the major BDNF isoform in the OB was the unprocessed BDNF precursor, proBDNF [13]. Neurotrophins are secreted as ‘pro’ isoforms (i.e.…”

“…Since the mouse OB expresses more proBDNF than it does mature BDNF [13], we sought to determine if both proBDNF and BDNF were active ligands in the mouse OB. Mitral cells were identified in OB slices as large, pyramidal cells in a discreet layer when viewed with infrared optics [33].…”

“…Activation of the insulin receptor kinase allows mitral cells to increase spike frequency and spike adaptation at higher amplitude current injections [33]. The fact that the unprocessed BDNF isoform, proBDNF [18], is more abundant in the mouse OB [13], [16], yet did not alter mitral excitability at any amplitude current injection indicates that mitral cells in vivo are likely to be surrounded by suitable concentrations of mature BDNF. The total amount of OB BDNF is still low in comparison to that measured in other brain regions [16], [40], [42].…”

“…BDNF immunohistochemistry revealed a selective loss of BDNF-immunoreactive fibers from the most superficial extent of the external plexiform layer [13]. This layer is known to shrink in size following naris occlusion [11], [16] and contains processes of glomerular interneurons [17].…”

Human Olfactory Perception

“…135 Work in mice provides evidence for an odour-elicited activity-based mechanism that enhances synaptogenesis of adult-born periglomerular neurons during their initial phases of development. 136 The reduction in odour-elicited sensory inputs due to deprivation could influence the dynamics and survival of synaptic connection at multiple stages in the olfactory pathway.…”