Preserving Cholinergic Neurons
ironjustice
impairment and cholinergic deficit in SAMP8 mice.
Brain Res. 2009 Oct 5.
Matsui N, Takahashi K, Takeichi M, Kuroshita T,
Noguchi K, Yamazaki K, Tagashira H, Tsutsui K,
Okada H, Kido Y, Yasui Y, Fukuishi N, Fukuyama Y,
Akagi M.
Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, 180 Nishihama-bouji,
Yamashiro-cho, Tokushima City, Tokushima 770-8514, Japan.
The therapeutic use of neurotrophic factors to treat
neurodegenerative disorders, including Alzheimer's disease,
is considered feasible.
Magnolol and honokiol, constituents of the Magnolia plant,
are small organic compounds with neurotrophic activity.
We investigated whether magnolol and honokiol can prevent
age-related learning and memory impairment and cholinergic
deficits in senescence-accelerated mice (SAM).
Magnolol (1, 10 mg/kg) or honokiol (0.1, 1 mg/kg) were orally
administered to SAMP8 mice once a day for 14 days in
2-month-old mice.
Learning and memory performance were evaluated by passive
avoidance tests and location and object novelty recognition
tests.
SAMP8 mice showed significant impairment of learning and
memory at 4 and 6 months of age.
This age-related learning and memory impairment was prevented
by pretreatment with either magnolol (10 mg/kg) or honokiol
(1 mg/kg).
Cholinergic neuron densities in the medial septum and vertical
limb of the diagonal band of the forebrain were evaluated by an
immunohistochemical analysis of choline acetyltransferase (ChAT).
SAMP8 mice showed a significant cholinergic deficit at 6 months
of age.
These age-related cholinergic deficits were prevented by treatment
with either magnolol (10 mg/kg) or honokiol (1 mg/kg).
Moreover, SAMP8 mice showed decreased activity of Akt, a member
of the pro-survival pathway, in the forebrain at 2 months of age.
A 14-day treatment with either magnolol (10 mg/kg) or honokiol
(1 mg/kg) enhanced phosphorylation of Akt in the forebrain at 2
months of age.
These results suggest that magnolol and honokiol prevent
age-related learning and memory impairment by preserving cholinergic
neurons in the forebrain.
These compounds may have potential therapeutic applications to
various neurodegenerative disorders.
PMID: 19815000
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