Ml. Boatell et al., TIME-RELATED CORTICAL AMINO-ACID CHANGES AFTER BASAL FOREBRAIN LESION- A MICRODIALYSIS STUDY, Journal of neurochemistry, 64(1), 1995, pp. 285-291
Cholinergic basal forebrain (BF) lesions in experimental animals have
been used as a potential model for cholinergic deficits in cortex and
hippocampus that occur in normal aging and Alzheimer's disease (AD). G
lutamatergic cortical neurons are also affected in AD and could be par
t of the neurodegenerative process. In the present study, the effect o
f bilateral BF lesion with ibotenic acid microinjection on cortical ex
tracellular amino acid levels was determined. Samples were collected e
very 20 min with microdialysis probes in awake, freely moving rats und
er basal and potassium stimulation conditions and measured by HPLC wit
h fluorescence detection. Microdialysis experiments were performed 13
days, 21 days, and 30 days after BF lesion. The effectiveness of the l
esion was shown by a significant 30% depletion in acetyl-CoA:choline O
-acetyltransferase (EC 2.3.1.6) activity in the frontal cortex. Under
basal conditions at 13 days only extracellular levels of taurine (Tau)
and Glu were significantly reduced. Tau and Glu levels were recovered
after 21 days and 30 days, respectively. In contrast, increase in Gly
levels reaches its significance only at 30 days after lesion. Signifi
cant increases of Gln levels were observed at 21 days and 30 days. Asp
and Ser levels remained constant throughout the period studied. Potas
sium stimulation led to increased Asp, Glu, Gly, and Tau levels, where
as Gin content decreased and Ser remained unaltered. As Ser is not bel
ieved to be a neurotransmitter, its lack of Variation in any of the ex
perimental conditions studied supports specific neuronal changes of th
e other amino acids. Results are discussed with reference to data obse
rved in AD patients and possible mechanisms underlying the changes are
suggested.