PMID- 9086508
OWN - NLM
STAT- MEDLINE
DCOM- 19970623
LR  - 20141120
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 17
IP  - 3-4
DP  - 1996 Fall-Winter
TI  - Rat brain mast cells: an in vitro paradigm for assessing the toxic effects of 
      neurotropic therapeutics.
PG  - 845-50
AB  - Neurotrophic factors (NTFs) such as nerve growth factor (NGF), brain-derived 
      neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) are currently 
      being explored as novel therapeutics in a range of neurodegenerative disorders 
      such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. To this end, 
      animal studies and clinical trials have been conducted to assess the toxic 
      effects of recombinant NTFs. It is apparent that both NGF and BDNF induce a range 
      of adverse effects, for example inflammation, hyperalgesia, and disturbances in 
      CNS biogenic amine levels which variously manifest as weight loss/gain, changes 
      in feeding behaviour and general malaise. It has been demonstrated that NGF 
      induces release of biologically active mediators, such as histamine, from rat 
      peritoneal mast cells (RPMC). However, whether other NTFs do likewise or indeed 
      are able to induce secretion from other mast cells types had not been explored. 
      We have developed a novel protocol for dispersing mast cells from rat brain 
      tissue, in particular the thalamus which contains the highest number of mast 
      cells in the adult rat. Rat brain mast cells (RBMC) released histamine in a 
      concentration dependent manner in response to NTFs, with a rank order of BDNF > 
      CNTF > NGF; in contrast RPMC were refractory to the effects of BDNF and CNTF. The 
      ability of NTFs to induce release of histamine (a neurotransmitter and 
      neuromodulator in the CNS) from RBMC may go some way to explain some of the 
      adverse effects apparent in vivo upon dosing with NTFs. Mast cells in vitro, and 
      brain mast cells in particular, offer the potential to screen novel NTFs for 
      their neuroimmunotoxic potential relevant to detecting likely clinical adverse 
      effects in humans.
FAU - Purcell, W M
AU  - Purcell WM
AD  - Cellular Toxicology Unit, University of Hertfordshire, Herts, U.K.
FAU - Westgate, C
AU  - Westgate C
FAU - Atterwill, C K
AU  - Atterwill CK
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Ciliary Neurotrophic Factor
MH  - Dose-Response Relationship, Drug
MH  - In Vitro Techniques
MH  - Male
MH  - Mast Cells/*drug effects
MH  - Nerve Growth Factors/*pharmacology
MH  - Nerve Tissue Proteins/pharmacology
MH  - Rats
MH  - Rats, Wistar
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1996 Fall-Winter;17(3-4):845-50.