PMID- 8636237
OWN - NLM
STAT- MEDLINE
DCOM- 19960711
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 133
IP  - 3
DP  - 1996 May
TI  - Neurotrophins promote the survival and development of neurons in the cerebellum 
      of hypothyroid rats in vivo.
PG  - 631-46
AB  - The development of cerebellar cortex is strongly impaired by thyroid hormone (T3) 
      deficiency, leading to altered migration, differentiation, synaptogenesis, and 
      survival of neurons. To determine whether alteration in the expression of 
      neurotrophins and/or their receptors may contribute to these impairments, we 
      first analyzed their expression using a sensitive RNAse protection assay and in 
      situ hybridization; second, we administered the deficient neurotrophins to 
      hypothyroid animals. We found that early hypothyroidism disrupted the 
      developmental pattern of expression of the four neurotrophins, leading to 
      relatively higher levels of NGF and neurotrophin 4/5 mRNAs and to a severe 
      deficit in NT-3 and brain-derived neurotrophic factor (BDNF) mRNA expression, 
      without alteration in the levels of the full-length tyrosine kinase (trk) B and 
      trkC receptor mRNAs. Grafting of P3 hypothyroid rats with cell lines expressing 
      high levels of neurotrophin 3 (NT-3) or BDNF prevented hypothyroidism-induced 
      cell death in neurons of the internal granule cell layer at P15. In addition, we 
      found that NT-3, but not BDNF, induced the differentiation and/or migration of 
      neurons in the external granule cell layer, stimulated the elaboration of the 
      dendritic tree by Purkinje cells, and promoted the formation of the mature 
      pattern of synaptic afferents to Purkinje cell somas. Thus, our results indicate 
      that both granule and Purkinje neurons require appropriate levels of NT-3 for 
      normal development in vivo and suggest that T3 may regulate the levels of 
      neurotrophins to promote the development of cerebellum.
FAU - Neveu, I
AU  - Neveu I
AD  - Department of Medical Biochemistry and Biophysics, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Arenas, E
AU  - Arenas E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Cell Death/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Survival/drug effects
MH  - Cell Transplantation
MH  - Cerebellum/cytology/growth & development
MH  - Female
MH  - Fibroblasts/cytology/physiology
MH  - Gene Expression Regulation, Developmental/physiology
MH  - Hypothyroidism/*physiopathology
MH  - Nerve Growth Factors/*genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Neurons/cytology/*drug effects
MH  - Neurotrophin 3
MH  - Purkinje Cells/cytology/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor Protein-Tyrosine Kinases/genetics
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptor, trkC
MH  - Receptors, Nerve Growth Factor/genetics
MH  - Synapses/physiology
MH  - Triiodothyronine/deficiency
PMC - PMC2120825
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
PMCR- 1996/11/01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PHST- 1996/11/01 00:00 [pmc-release]
AID - 96222366 [pii]
AID - 10.1083/jcb.133.3.631 [doi]
PST - ppublish
SO  - J Cell Biol. 1996 May;133(3):631-46. doi: 10.1083/jcb.133.3.631.