Related Experiment Video
Updated: Mar 8, 2026
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
Leukemia inhibitory factor impairs structural and neurochemical development of rat visual cortex in vivo
Maren Engelhardt1, Graziella di Cristo2, Jochen Grabert3
1Developmental Neurobiology, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Germany; Institute of Neuroanatomy, Medical Faculty Mannheim, CBTM, Heidelberg University, Germany.
Insights
Leukemia inhibitory factor (LIF) delays cortical neuron maturation and growth, impacting neurotrophin signaling. This cytokine interferes with the development of both excitatory and inhibitory neurons during critical developmental periods.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- The critical period in visual cortex development is crucial for neuronal maturation.
- Proinflammatory cytokines, such as leukemia inhibitory factor (LIF), are known to influence neuronal development.
- Developing cortical neurons rely on neurotrophins for growth and differentiation.
Purpose of the Study:
- To investigate the effects of LIF on the somatic maturation of cortical neurons in vivo and in vitro.
- To determine how LIF influences the expression of specific neurochemical markers in developing cortical neurons.
- To explore the interaction between LIF and neurotrophin signaling in cortical neuron development.
Main Methods:
- In vivo minipump infusions of LIF into the visual cortex of rodents during the critical period.
- In vitro treatment of organotypic cortical cultures with LIF.
- Analysis of neuronal somatic maturation and expression of specific proteins and mRNAs (NPY, parvalbumin, Kv3.1, calbindin D-28k, GAD-65/67, calretinin).
Main Results:
- LIF infusion in vivo and LIF treatment in vitro inhibited somatic maturation of pyramidal neurons and GABA-ergic interneurons.
- LIF altered the expression of several key neurochemical markers, including increased NPY and decreased parvalbumin, Kv3.1, calbindin D-28k, and GAD-65.
- LIF treatment interfered with the growth-promoting effects of neurotrophin-4 on GABA-ergic neurons.
Conclusions:
- LIF significantly inhibits the somatic maturation and neurochemical differentiation of developing cortical neurons.
- LIF may counteract neurotrophin-dependent neuronal growth and differentiation by altering neurotrophin expression and/or signaling pathways.
- These findings highlight LIF as a critical modulator of cortical development with potential implications for understanding developmental disorders.
Abstract:
Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo. Likewise, DIV 12-20 LIF treatment in organotypic cultures prevents somatic growth GABA-ergic neurons. Further, while NPY expression is increased in the LIF-infused hemispheres, the expression of parvalbumin mRNA and protein, Kv3.1 mRNA, calbindin D-28k protein, and GAD-65 mRNA, but not of GAD-67 mRNA or calretinin protein is substantially reduced. Also, LIF treatment decreases parvalbumin, Kv3.1, Kv3.2 and GAD-65, but not GAD-67 mRNA expression in OTC. Developing cortical neurons are known to depend on neurotrophins. Indeed, LIF alters neurotrophin mRNA expression, and prevents the growth promoting action of neurotophin-4 in GABA-ergic neurons. The results imply that LIF, by altering neurotrophin expression and/or signaling, could counteract neurotrophin-dependent growth and neurochemical differentiation of cortical neurons.
