Premium
NT‐4/5 and LIF, but not NT‐3 and BDNF, promote NPY mRNA expression in cortical neurons in the absence of spontaneous bioelectrical activity
Author(s) -
Wirth Marcus J.,
Obst Kirstin,
Wahle Petra
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00157.x
Subject(s) - cortical neurons , neuroscience , neurotrophin , brain derived neurotrophic factor , psychology , chemistry , neurotrophic factors , biochemistry , receptor
Epigenetic factors are known to influence the differentiation of neocortical neurons. The present study analyses the role of spontaneous bioelectrical activity (SBA) and neurotrophic factors on the expression of neuropeptide Y (NPY) in rat visual cortical neurons using organotypic monocultures prepared from newborn animals and in situ hybridization to detect the NPY messenger ribonucleic acid (mRNA). Spontaneously active cortex cultures display NPY mRNA expression in about 7% of all cortical neurons from 10 days in vitro (DIV) on. Blocking the SBA by chronic application of 10 m m Mg 2+ for 3–30 DIV reduces the percentage of NPY neurons to about 2%. Allowing an initial phase of SBA (1–20 DIV) followed by an SBA blockade (for 21–50 DIV) results in 2% labelled neurons, indicating a dramatic reduction of NPY mRNA expression in the absence of SBA. Surprisingly, the reverse experiment (a period of SBA blockade for 1–20 DIV followed by a period of SBA recovery for 21–40 DIV) does not cause an upregulation of NPY mRNA expression. However, allowing cultures to differentiate as spontaneously active cultures, then applying a transient period of SBA blockade which is followed by a second period of SBA, does rescue the NPY mRNA expression in 7% of the cortical neurons. We conclude that SBA is a main trigger for NPY mRNA expression and it is particularly important during an early postnatal period of differentiation. We then analysed whether neurotrophic factors known to modulate cortical neuropeptide expression are able to do so in the absence of SBA. Supplementing chronically blocked cultures with the neurotrophins, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), neurotrophin‐4/5 (NT‐4/5) and the cytokine, leukaemia inhibitory factor (LIF), reveals that BDNF and NT‐3 are unable to increase the percentage of NPY neurons. In contrast, LIF and NT‐4/5 increase the percentage of NPY neurons to 4 and 6–7%, respectively. Moreover, neurons treated with NT‐4/5 display a very high level of NPY mRNA expression in somata and in the dendritic trees. The data suggest a complex interplay and a hierarchy of epigenetic factors in regulating the neurochemical architecture of the developing neocortex.