Educación Médica Continua

The first language of baby is touch. Módulo 2: Desarrollo neurológico de la piel.

Influence of age on neurotrophic activity of juvenile and adult keratinocytes

While the development of barrier function is well documented, little is known about the interactions between nervous system and skin cells during skin maturation. In particular, the development and the maintenance of nervous fibers during skin maturation in the first age is not known.

The Epidermal nerve endings density in 20 healthy children (7-17 years old), as determined by punch biopsy and suction blister, is more than 3 times higher than that found in similar studies of normal adults.  This density is lower in young children than in older children (P < 0.01), with no difference between boys and girls (P = 0.92)

The objectives of our studies were

• To explore the evolution of neurosensory system in juvenile skin
• To investigate the influence of keratinocytes of different ages on the development of sensory neurons in culture

Mechanoreceptors and nervous fibers are colocalized

IMMUNOFLUORESCENCE OF ADULT SKIN EXPLANTS*

*Obtained from plastic surgery

Construction of cutaneous innervation during infancy: organization

IMMUNOFLUORESCENCE OF  SKIN EXPLANTS*

*Obtained from plastic surgery

Meissner corpuscule is less organized in infant than in adult. Maturation of sensorial system in children.

Construction of cutaneous innervation during infancy: density

*Obtained from plastic surgery

**Panoutsopoulou IG et al. Muscle Nerve. 2015 ; 51 378-384.

Construction of cutaneous innervation during infancy:

role of keratinocytes -> comparison to adults

Construction of cutaneous innervation during infancy: increased role in skin construction vs adults

Methods: Transcriptomic analysis of skin barrier genes in re-innervated juvenile epidermis vs adults.

SKIN CONSTRUCTION, HEALING

Juvenile keratinocytes produce more neuronal trophic factors than adult

Development of first baby innervated skin model (2)

EPIDERMAL EXPLANTS

Objectives: new model

• To understand pediatric cutaneous neurobiology
• To develop products adapted to baby skin sensoriality

1st STEP: Differentiation of IPS into neurons(2)

VERIFICATION OF ELECTRIC ACTIVITY AFTER STIMULATION WITH LACTIC ACID

2nd STEP: Innervation of adult epidermis(2)

• More neurons (green) and better dispatched in epidermis at day 6.
• Neurons are able to innervate the epidermis.

3rd STEP: Effects of innervation on adult epidermis(2)

• Neurons increase epidermal quality ( Increased number of epidermal nuclei)
• Neurons allow
• Proliferation
• Apoptosis
• Stem Cells

4TH STEP: Innervation of infant epidermis (play video)

5th STEP: Comparison of juvenile and adults results(2)

COMPARISON TO ADULTS

Gene expression of claudin (cl) 1-2-3, zonula occludens (zo) 1-2, junctional adhesion

molecule (jam) 1, e-cadherin (e-cad), desmocoline, desmoglein

• Gene expression of barrier markers in juvenile re-innervated epidermis is increased compared to adult
• Skin barrier barrier markers juvenile vs adults

Conclusion of EV.E.I.L.S contribution to new models of skin innervation during infancy

• Epidermal innervation is present and is immature in infants.
• Epidermal neurons density is higher: this may be due to a stronger attraction of juvenile keratinocytes to constructs skin barrier.
• For the first time, reconstructed  juvenile innervated skin showed that neurons play a major role in the construction of skin barrier of babies.
• This ongoing research is the first step to better understand skin sensoriality in children and to design for them  products with high sensorial qualities.

REFERENCIAS:

1 Panoutsopoulou IG, et al. Epidermal innervation in healthy children and adolescents. Muscle Nerve. 2015  ; 51: 378–384.

2 Pr L.Misery Coordinateur et clinicien de centre expert de Dermatologie et Vénérologie CHRU de Brest – Hôpital Morvan, France