Increased vulnerability of septal cholinergic neurons to partial loss of target neurons in aged rats
Section snippets
Animals and surgical procedures
Thirty-two young adult (four to six months) and aged (24–30 months) male Sprague–Dawley rats from the same ( in house) breeding colony were used in this study. The animals were not behaviourally characterized and were assigned randomly to experimental groups: two groups of young adults (n = 7 per group) and two groups of aged rats (n = 9 per group). Under ketamine and xylazine anaesthesia, each animal was given nine stereotaxically placed injections of either N-methyl-d-aspartate (NMDA) solution or
Degree of excitotoxic ablation of hippocampus
In both young adult and aged rats, injection of vehicle did not significantly change hippocampal surface area, whereas unilateral injection of the excitotoxic amino acid NMDA at the dosing regimen used in this study caused a partial reduction in the mean hippocampal surface area of 55–60% relative to the uninjected sided (Table 1, Fig. 1). Analysis of variance with post hoc pairwise tests confirmed the significance of the differences in mean hippocampal surface area between vehicle- and
Discussion
These findings show that in aged rats partial loss of hippocampal target tissue can lead to degenerative changes in septal cholinergic neurons in the form of substantial cell shrinkage and a pronounced down-regulation of intracellular levels of the transmitter-synthesizing enzyme ChAT. In young adult rats, partial loss of target tissue to a similar degree caused only a small cell shrinkage of septal cholinergic neurons, and did not cause a reduction in staining intensity. These findings
Conclusions
The observations of this study suggest that basal forebrain cholinergic neurons react more severely to the loss of their target neurons and are more vulnerable to disturbances of neuron–target interactions in aged than in young adult animals. This increased vulnerability may contribute to the degenerative changes exhibited by basal forebrain cholinergic neurons in ageing and age-related conditions such as Alzheimer's disease.
Acknowledgements
The authors thank K. J. Baker and S. J. Stevens for expert technical assistance and J. Bashford for photography. This work was supported by grants from MRC, the Wellcome Trust and Merck, Sharp and Dohme Research Laboratories.
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Neurokinin3-R agonism in aged rats has anxiolytic-, antidepressant-, and promnestic-like effects and stimulates ACh release in frontal cortex, amygdala and hippocampus
2011, European NeuropsychopharmacologyCitation Excerpt :A decline in cholinergic activity in the brain has been observed during aging (Araujo et al., 1990; Takei et al., 1989). Also, cholinergic projection neurons in the basal forebrain undergo significant atrophy in the aged rodent (Cooper and Sofroniew, 1996; De Lacalle et al., 1996). The degree of atrophy is highly correlated with the cognitive impairment (Armstrong et al., 1988; Gage et al., 1988).
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Present address: Department of Neurochemistry, Max-Planck-Institute for Psychiatry, Am Klopferspitz 18A, D-82152 Planegg-Martinsried, Germany.