PMID- 15713342
OWN - NLM
STAT- MEDLINE
DCOM- 20050503
LR  - 20161124
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 26
IP  - 2
DP  - 2005 Mar
TI  - Fumonisin B1-induced neurodegeneration in mice after intracerebroventricular 
      infusion is concurrent with disruption of sphingolipid metabolism and activation 
      of proinflammatory signaling.
PG  - 211-21
AB  - Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, causes 
      equine leukoencephalomalacia, a condition not reproduced in any other species. We 
      hypothesized that direct exposure of murine brain to FB1 will result in 
      neurotoxicity, characterized by biochemical and pathological alterations. The 
      present study compared the toxicity of FB1 in mouse brain after an 
      intracerebroventricular (icv) or subcutaneous (sc) infusion. Female BALB/c mice 
      (5/group) were infused (0.5 microl/h) with total doses of 0, 10 or 100 microg FB1 
      in saline over 7 days via osmotic pumps implanted either via icv cannulation of 
      the ventricle or via the sc route. One day after the last day of treatment, 
      brains were dissected either fresh or after intracardiac paraformaldehyde 
      fixation. In mice given 100 microg of FB1 icv, FluoroJade B staining revealed 
      neurodegeneration in the cortex, and anti-glial fibrillary acidic protein 
      staining detected activated astrocytes in the hippocampus. High performance 
      liquid chromatography indicated accumulation of free sphinganine in animals given 
      FB1 icv in all brain regions and increased free sphingosine after the 100 microg 
      FB1 in the cortex. The concentration of cortical sphingomyelin and complex 
      sphingolipids remained unchanged. The icv administration of FB1 induced 
      expression of tumor necrosis factor alpha, interleukin-1beta, interleukin-6 and 
      interferon gamma after both doses, assayed by the real-time polymerase chain 
      reaction. The sc administration of 100 microg FB1 caused slight sphinganine 
      accumulation and increased IL-1beta expression in cortex only. Results indicated 
      that icv injection of FB1 caused neurodegeneration with simultaneous inhibition 
      of de novo ceramide synthesis, stimulation of astrocytes, and upregulation of 
      pro-inflammatory cytokines in the murine brain. A relative lack of FB1 
      availability into the brain could be responsible for the absence of its 
      neurotoxicity in mouse.
FAU - Osuchowski, Marcin F
AU  - Osuchowski MF
AD  - Department of Physiology and Pharmacology, College of Veterinary Medicine, The 
      University of Georgia, Athens, GA 30602-7389, USA.
FAU - Edwards, Gaylen L
AU  - Edwards GL
FAU - Sharma, Raghubir P
AU  - Sharma RP
LA  - eng
GR  - ES 09403/ES/NIEHS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Fumonisins)
RN  - 0 (Sphingolipids)
RN  - 3ZZM97XZ32 (fumonisin B1)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Female
MH  - Fumonisins/*administration & dosage/toxicity
MH  - Inflammation/chemically induced/*metabolism
MH  - Injections, Intraventricular
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neurodegenerative Diseases/chemically induced/*metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Sphingolipids/*metabolism
EDAT- 2005/02/17 09:00
MHDA- 2005/05/04 09:00
CRDT- 2005/02/17 09:00
PHST- 2004/07/06 00:00 [received]
PHST- 2004/10/04 00:00 [accepted]
PHST- 2005/02/17 09:00 [pubmed]
PHST- 2005/05/04 09:00 [medline]
PHST- 2005/02/17 09:00 [entrez]
AID - S0161-813X(04)00137-8 [pii]
AID - 10.1016/j.neuro.2004.10.001 [doi]
PST - ppublish
SO  - Neurotoxicology. 2005 Mar;26(2):211-21. doi: 10.1016/j.neuro.2004.10.001.