Protection against impairment of memory and immunoreactivity in senescence-accelerated mice by acidic fibroblast growth factor.
Subcutaneous injection of aFGF once a week into senescence-accelerated mice (SAM)P8 was begun at 3 weeks after birth and continued for 10 months. Saline was injected as a control. Learning and memory and cellular immunological functions in the aFGF group were enhanced significantly, while those of the saline group deteriorated. 1. The number of cholinergic neurons was decreased by less than 20% and choline acetyltransferase activity in individual neurons in the medical septum which send monosynaptic terminals to the hippocampus was significantly decreased in the saline group, but not so much in the aFGF group. 2. The respective densities of muscarinic and NMDA receptors and the aFGF receptor, i.e., FGFR-1 on the hippocampal neurons were also significantly higher in the aFGF group than in the saline group. 3. The long-term potentiation in the hippocampal slice preparations after a brief tetanic stimulation at the Schaffer collateral/commissural afferents was significantly facilitated in the aFGF group, but not in the saline group. 4. These data indicate the normalization caused by aFGF of the medial septohippocampal circuit, which is necessary for learning and memory. 5. The delayed type hypersensitivity reactions (DTH) in the footpad caused by challenge with trinitrophenyl or sheep red blood cells as measured at the end of the 2nd and 7th months, indicated the T cell immune response. Both types of DTHs were reduced in the 7th month as compared with the 2nd month in the saline group, but the aFGF group was protected against this reduction in accordance with age. 6. These results show that aFGF provides protection against impairment of not only learning and memory but also DTH immunoreactivity in SAMP8. They also indicate a close relationship between learning and memory and T cell immune function.
Oomura
Y
Y
Institute of Bio-Active Science, Nippon Zoki Pharmaceutical Co., Hyogo, Japan.
Sasaki
K
K
Li
A
A
Yoshii
H
H
Fukata
Y
Y
Yago
H
H
Kimura
H
H
Tooyama
I
I
Hanai
K
K
Nomura
Y
Y
Yanaihara
N
N
D000375:Aging / Q000276:immunology*; D000818:Animals; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D016220:Fibroblast Growth Factor 1