Re-establishing the regenerative potential of central nervous system axons in postnatal mice.

• At a certain point in development, axons in the mammalian central nervous system lose their ability to regenerate after injury. Using the optic nerve model, we show that this growth failure coincides with two developmental events: the loss of Bcl-2 expression by neurons and the maturation of astrocytes. Before postnatal day 4, when astrocytes are immature, overexpression of Bcl-2 alone supported robust and rapid optic nerve regeneration over long distances, leading to innervation of brain targets by day 4 in mice. As astrocytes matured after postnatal day 4, axonal regeneration was inhibited in mice overexpressing Bcl-2. Concurrent induction of Bcl-2 and attenuation of reactive gliosis reversed the failure of CNS axonal re-elongation in postnatal mice and led to rapid axonal regeneration over long distances and reinnervation of the brain targets by a majority of severed optic nerve fibers up to 2 weeks of age. These results suggest that an early postnatal downregulation of Bcl-2 and post-traumatic reactive gliosis are two important elements of axon regenerative failure in the CNS.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Animals

Animals

Newborn

Astrocytes

cytology

metabolism

Axons

metabolism

Blotting

Western

Brain

metabolism

Central Nervous System

physiology

Coculture Techniques

DNA Primers

chemistry

Down-Regulation

Female

Glial Fibrillary Acidic Protein

metabolism

Gliosis

Humans

Male

Mice

Mice

Inbred C57BL

Mice

Transgenic

Microscopy

Electron

Transmission

Microscopy

Fluorescence

Models

Anatomic

Nerve Regeneration

Neurons

metabolism

Optic Nerve

anatomy & histology

metabolism

pathology

physiology

Proto-Oncogene Proteins c-bcl-2

metabolism

physiology

Retina

metabolism

Reverse Transcriptase Polymerase Chain Reaction

Transgenes

Vimentin

metabolism

Publication and Content Type

ref (subject category)

art (subject category)