Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins.
This study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double-labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL-positive cells are thalamocortical neurons. The number of TUNEL-positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion-induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion-induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival-promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher-order neurons in the somatosensory system during the period of fine-tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.
Baldi
A
A
Laboratory of Neuroscience, Department of Physiology and Neuroscience, Libera Università 'Campus Bio-Medico', Rome, Italy.
Calia
E
E
Ciampini
A
A
Riccio
M
M
Vetuschi
A
A
Persico
A M
AM
Keller
F
F
D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001370:Axonal Transport / Q000187:drug effects; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002452:Cell Count; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D003423:Critical Period, Psychological; D020287:In Situ Nick-End Labeling; D008442:Maxillary Nerve / Q000166:cytology / Q000502:physiology; D008854:Microscopy, Electron; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology*; D051381:Rats; D011917:Rats, Inbred Lew; D013003:Somatosensory Cortex / Q000166:cytology*; D013787:Thalamic Nuclei / Q000166:cytology*; D014747:Vinblastine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D019208:Brain-Derived Neurotrophic Factor; D002843:Chromatin; D014747:Vinblastine; D020932:Nerve Growth Factor