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/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.
Cite this paper
R. Freddi, P. Duca, M. Mariotti and I. Gritti, "Behaviour and Degenerative Changes in the Basal Forebrain Systems of Aged Rats (12 Months Old) after Levo-Acetyl-Carnitine Treatments," Journal of Behavioral and Brain Science, Vol. 2 No. 1, 2012, pp. 18-25. doi: 10.4236/jbbs.2012.21003.
 A. P. Burlina, H. Sershen, E. A. Debler and A. Lajtha, “Uptake of Acetyl-L-Carnitine in the Brain,” Neurochemical Research, Vol. 14, No. 5, 1989, pp. 489-493.
 L. Janiri, M. Falcone, A. Persico and E. Tempesta, “Activity of L-Carnitine and L-Acetylcarnitine on Cholinoceptive Neocortical Neurons of the Rat in Vivo,” Journal of Neural Transmission, Vol. 86, No. 2, 1991, pp. 135-146.
 L. Battistin, G. Pizolato, M. Dam, C. DaCol, C. Perlotto, N. Saitta, N. Borsato, M. Calvani, G. Ferlin, “Single-Proton Emission Computed Tomography Studies with 99mTc-Hexamethylpropyleneamine Oximine in Dementia: Effects of Acute Administration of L-Acetylcarnitine,” Europeane Neurology, Vol. 29, No. 5, 1989, 261-265.
 A. Carta, M. Calvani, D. Bravi and S. N. Bhuachalla, “Acetyl-L-Carnitine and Alzheimer’s Disease: Pharmacological Considerations beyond the Cholinergic Sphere,” Annlas of the New York Academy of Science, Vol. 695, 1993, pp. 324-326. doi:10.1111/j.1749-6632.1993.tb23077.x
 C. Ori, U. Freo, G. Pizzolato and M. Dam, “Effects of Acetyl-L-Carnitine on Regional Cerebral Glucose Metabolism in Awake Rats,” Brain Research, Vol. 951, No. 2, 2002, pp. 330-335. doi:10.1016/S0006-8993(02)03290-0
 M. Schieppati, I. Gritti, R. Mazzocchio, A. Rossi and M. Mancia, “Motoneurone Recurrent Inhibition Is Enhanced by L-Acetylcarnitine in Humans,” Electromyography and Clinical Neurophysiology, Vol. 29, No. 2, 1989, pp. 73-80.
 M. Schieppati, I. Gritti and C. Romanò, “Recurrent and Reciprocal Inhibition of the Human Monosynaptic Reflex Shows Opposite Changes Following Intravenous Administration of Acetylcarnitine,” Acta Physiologica Scandinavica, Vol. 143, No. 1, 1991, pp. 27-32.
 G. Traina, G. Federighi, M. Macchi, R. Bernardi, M. Durante and M. Brunelli, “Modulation of Myelin Basic Protein Gene Expression by Acetyl-L-carnitine,” Molecular Neurobiology, Vol. 44, No. 1, 2011, pp. 1-6.
 M. Youle and M. A. Osio, “Double-Blind, Parallel-Group, Placebo-Controlled, Multicentre Study of Acetyl-L-Carnitine in the Symptomatic Treatment of antiretroviral Toxic Neuropathy in Patients with HIV-1 Infections,” HIV Medicine, Vol. 8, No. 4, 2007, pp. 241-250.
 S. Koh and R. Loy, “Age-Related Loss of Nerve Growth Factor Sensitivity in Rat Basal Forebrain Neurons,” Brain Research, Vol. 440, No. 2, 1988, pp. 396-401.
 S. Koh, P. Chang, J. T. Collier and R. Loy, “Loss of NGF Receptors Immunoreactivity in Basal Forebrain Neurons of aged Rats: Correlation with Spatial Memory Impairment,” Brain Research, Vol. 498, No. 2, 1989, pp. 397-404. doi:10.1016/0006-8993(89)91125-6
 P. Piovesan, L. Pacifici, G. Taglialatela, M. T. Ramacci and L. Angelucci, “Acetyl-L-Carnitine Treatment Increases Choline Acetyltransferase Activity and NGF Levels in the CNS of Adult Rats Following Total Fimbria-Fornix Transaction,” Brain Research, Vol. 633, No. 1-2, 1994, pp. 77-82. doi:10.1016/0006-8993(94)91524-5
 G. Taglialatela, A. Caprioli, A. Giuliani and O. Ghirardi, “Spatial Memory and NGF Levels in Aged Rats: Natural Variability and Effects of Acetyl-L-Carnitine Treatment,” Experimental Gerontology, Vol. 31, No. 5, 1996, pp. 577-587. doi:10.1016/0531-5565(96)00052-6
 A. L. Markowska, D. K. Ingram, C. A. Barnes, E. L. Spangler, V. J. Lemken, H. Kametani, W. Yee and D. S. Olton, “Acetyl-L-carnitine 1: Effects on Mortality, Pathology and Sensory Motor Performance in Aging Rats,” Neurobiology of Aging, Vol. 11, No. 5, 1990, pp. 491-497.
 R. Freddi, P. Duca, I. Gritti, M. Mariotti and M. Vertemati, “Behavioural and Degeneration Changes in the Basal Forebrain Systems of Aged Rats: A Quantitative Study in the Region of the Basal Forebrain after Levo-Acetyl-Carnitine Treatments Assessed by Abercrombie Estimation,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 33, No. 3, 2009, pp. 419-426.
 G. M. Gilad, J. M. Rabey, Y. Tizabi and V. H. Gilad, “Age-Dependent Loss and Compensatory Changes of Septohippocampal Cholinergic Neurons in Two Rat Strains Differing in Longevity and Response to Stress,” Brain Research, Vol. 436, No. 2, 1987, pp. 311-322.
 V. N. Luine, K. J. Renner, S. Heady and K. J. Jones, “Age and Sex-Dependent Decreases in ChAT in Basal Forebrain Nuclei,” Neurobiology of Aging, Vol. 7, No. 3, 1986, 193-198. doi:10.1016/0197-4580(86)90042-4
 J. E. Springer, M. W. Tayrien and R. Loy, “Regional Analysis of Age-Related Changes in the Cholinergic System of the Hippocampal Formation and Basal Forebrain of the Rat,” Brain Research, Vol. 407, No. 1, 1987, pp. 180-184.
 R. Strong, P. Hicks, L. Hsu, R. T. Bartus and S. J. Enna “Age-Related Alterations in the Rodent Brain Cholinergic System and Behaviour,” Neurobiology of Aging, Vol. 1, No. 1, 1980, pp. 59-63.
 J. C. Hornberger, S. J. Buell, D. G. Flood, T. H. McNeill and P. D. Coleman, “Stability of Numbers but Not Size of Mouse Forebrain Cholinergic Neurons to 53 Months,” Neurobiology of Aging, Vol. 6, No. 4, 1985, pp. 269-275.
 I. Gritti, L. Mainville, M. Mancia and B. E. Jones, “GABA-ergic and Other Non-Cholinergic Basal Forebrain Neurons Project to Meso- and Iso-Cortical Regions in the Rat,” The Journal of Comparative Neurology, Vol. 383, No. 2, 1997, pp. 163-177.
 I. Gritti, L. Mainville, I. Manns and B. E. Jones, “Parvalbumin-, Calbinding- or Caleretinin- in Cortically Projecting and GABAergic, Cholinergic or Glutamatergic Basal Forebrain Neurons of the Rat,” The Journal of Comparative Neurology, Vol. 458, No. 1, 2003, pp. 11-31.
 I. Gritti, L. Mainville and B. E. Jones, “Projections of GABAergic and Cholinergic Basal Forebrain and GABA-ergic Preoptic-Anterior Hypothalamic Neurons to the Posterior Lateral Hypothalamus of the Rat,” The Journal of Comparative Neurology, Vol. 339, No. 2, 1994, pp. 251-268. doi:10.1002/cne.903390206
 I. Gritti, L. Mainville and B. E. Jones, “Codistribution of GABA- with Acetylcholine-Synthesizing Neurons in the Basal Forebrain of the Rat,” The Journal of Comparative Neurology, Vol. 329, No. 4, 1993, pp. 438-457.
 I. Gritti, P. Henny, F. Galloni, L. Mainville, M. Mariotti and B. E. Jones, “Stereological Estimates of Basal Forebrain Cell Populations in the Rat, Including Neurons Containing Choline Acetyl-Transferase (ChAT), Glutamic Acid Decarboxylase (GAD) or Phosphate-Activated Glutaminase (PAG) and Colocalizing Vesicular Glutamate Transporters (VgluTs),” Neuroscience, Vol. 143, No. 4, 2006, pp. 1051-1064.
 R. Mietinen, G. Kalesnykas and E. H. Koivisto, “Estimation of the Total Number of Cholinergic Neurons Containing Estrogen Receptor-α in the Rat,” The Journal of Histochemistry and Citochemistry, Vol. 50, No. 7, 2002, pp. 891-902.
 R. G. M. Morris, “Developments of water-Maze Procedure for Studying Spatial Learning in the Rat,” Journal of Neuroscience Methods, Vol. 11, No. 1, 1984, pp. 47-67.
 G. Taglialatela, D. Navarra, R. Cruciani, M. T. Ramacci, G. S. Alema and L. Angelucci, “Acetyl-L-Carnitine Treatment Increases Nerve Growth Factor Levels and Choline Acetyltransferase Activity in the CNS of Aged Rats,” Experimental Gerontology, Vol. 29, No. 1, 1994, pp. 55-66. doi:10.1016/0531-5565(94)90062-0
 O. Ghirardi, S. Milano, M. T. Ramacci and L. Angelucci, “Effect of Acetyl-L-Carnitine Chronic Treatment on Discrimination Models in Aged Rats,” Physiology & Behavior, Vol. 44, No. 6, 1988, pp. 769-773.