Abstract
One group of six male control rats [12 months old] and one group of six male rats of the same age, singularly maintained in a cage, and treated with acetyl-L-carnitine-HCl [(gamma-trimethyl-beta-acetyl-butyrobetaine-HCl: Sigma-Tau code ST200 or ALCAR: 60 mg/kg/day[7]/po)] for six months were tested in the spatial learning/memory Morris mazewater task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Freddi et al., 2009]. Coronal sections 25 ?m thick were cut through the BF regions and processed every 200 ?m for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (average ± SD 28.3 ± 12.4 s vs. 61.16 ± 4.67 s; t = 6.07, DOF = 10, P = 0.0001). Degenerative morphological changes in the BF ChAT-positive cells were observed in the substantia innominata pars anterior of the control rats but not in the treated animals (P < 0.05). In the BF, the counted and estimated average number of ChAT + cells in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12+ [Nos. 2,3,4]) was higher but not significantly (15.288 ± 3281) than that counted and estimated in the 12-month-old control rats [(ChAT-CT-12 [Nos. 1,2,3]) (11.508 ± 3868), t = 1.82, DOF = 10, P = 0.319]. In the substantia innominata pars posterior, the ChAT+ cells were significantly more numerous (P < 0.05) in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12 + [Nos. 2,3,4]) than in the control rats (ChAT-CT-12 [Nos. 1,2,3]). Above all, these results dem-onstrate that treatment with ALCAR from the age of 6 up to 12 months significantly attenuated spatial learning/memory impairment on the Morris maze-water behavioral task (P < 0.001) and also importantly reduced degeneration in size and number of cholinergic cells in the nucleus basalis magnocellularis of the BF. Accordingly, the surviving cholinergic neurons found in the BF of the ALCAR-treated rats might play an important role in modulating cortical activity and facilitating processes of attention, learning and memory.
Highlights
Acetyl-L-carnitine ([ALCAR] gamma-trimethyl-beta-acetyl-butyrobetaine-hydrochloride, Sigma-Tau code: ST200) is the metabolically active form of acetylcarnitine present in the central nervous system (CNS)
Cholinergic cells account for only 5% - 6% of the total population of the basal forebrain (BF), this study focused on: 1) the topographical location and severity of cholinergic deficit in 12-month-old rats with impaired performance on the spatial/learning Morris water-maze test; and 2) the effect of acetyl-L-carnitine treatment on rats aged from 6 to 12 months to see whether this neuropsychopharmacological compound can significantly attenuate spatial learning/memory impairment on the Morris maze-water task [13] and significantly reduce degeneration of the largest cholinergic neurons in the seven myelo- and cytoarchitecturally defined BF regions [15,24,25,26]
This study confirmed that the 12-month-old control rats with impaired spatial learning and memory performance on the Morris water-maze test [13,28] had significantly smaller and fewer BF cholinergic neurons than the ALCAR-treated rats [16]
Summary
Acetyl-L-carnitine ([ALCAR] gamma-trimethyl-beta-acetyl-butyrobetaine-hydrochloride, Sigma-Tau code: ST200) is the metabolically active form of acetylcarnitine present in the central nervous system (CNS). ALCAR acts as a shuttle for long-chain fatty acids between the cytoplasm and the mitochondria, is involved in the production of cellular energy and the removal of toxic accumulation of fatty acids from the mitochondria. It is actively transported across the blood-brain barrier and displays affinities for GABAergic and L-glutamate carriers [1]. Contrasting data about the age-dependent cholinergic cell BF decline have been reported by Horneberger et al [20], who noted that aging causes a progressive shrinkage of AChE positive neurons in the BF nuclei, which was most pronounced in the nucleus basalis magnocellularis; the number of JBBS
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