Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75ntr receptors? a study using 192 IgG-saporin lesions in rats

Birthelmer, Anja; Lazaris, Anelise; Riegert, Céline; Pereira, Patricia Marques; Koenig, Julie; Jeltsch, Hélène; Jackisch, Rolf; Cassel, J.C.

doi:10.1016/j.neuroscience.2003.09.001

Cited by 12 publications

(10 citation statements)

References 36 publications

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“…Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by deficits in cognitive function associated with an impaired cholinergic nervous system [1]. The cholinergic hypothesis states that a loss of the cholinergic function in the central nervous system (CNS) contributes significantly to the cognitive decline associated with advanced age and AD [2].…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function

Lee¹,

Yun²,

In³

et al. 2011

Journal of Ginseng Research

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This study evaluated cholineresterase inhibitory activity of Korean white ginseng extract (WGE), red ginseng extract (RGE), and black ginseng extract (BGE) and the cholinergic effect on scopolamine (SCOP)-induced amnesic mice. WGE, RGE, and BGE inhibited acetylcholineserase (AChE), as well as butyrylcholineserase (BuChE) in a concentration-dependent manner. BGE presented strong inhibition of AChE with an IC50 value of 1.72 mg/mL, followed by WGE (5.89 mg/mL), RGE (6.30 mg/mL), respectively. The inhibitory activity of the three ginseng extracts on BuChE showed similar values among the groups. To better understand the mechanisms of the possible effect of ginseng extract on the cholinergic function, this study assessed the expression of the cholinergic markers of choline acetyltransferase (ChAT) and AChE using western blot and RT-PCR analysis in the brains of amnesic mice. Treatment with ginseng extracts led to inhibition of AChE expression and, the activation of ChAT expression in the hippocampus and the cerebral cortex of amnesic mice as induced by SCOP. The results suggest that ginseng extracts including BGE, appear to modulate the metabolism of acetylchoine (ACh), which would greatly increase synaptic ACh levels and most potently revert SCOP-induced amnesia.

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Section: Introductionmentioning

confidence: 99%

Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function

Lee¹,

Yun²,

In³

et al. 2011

Journal of Ginseng Research

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“…The concentration of ACh was also severely reduced in both the dorsal and the ventral hippocampus (by about 80%; see Table 2), similar to that found in a previous study at a shorter postsurgery delay (Lehmann et al, 2002a), and less markedly reduced in cortical regions (about À45% in prefrontal and frontoparietal cortices). The reduced AChE staining and lower ACh concentration in the septal region is a further confirmation of damage to septal cholinergic neurons, although cholinergic markers may be conserved in this region due to extrinsic, i.e., brain stem, cholinergic innervation processes that remain unaffected (Birthelmer et al, 2003). Partial denervation of the cortex is also consistent with damage of septo-cortical cholinergic neurons, as they innervate the primary and secondary motor, sensory motor, and visual cortices (Mesulam et al, 1983;Amaral and Kurz, 1985), but may also reflect some diffusion of the immunotoxin to the cholinergic cells at the adjacent nucleus basalis and substantia innominata (Gaykema et al, 1990).…”

Section: Discussionmentioning

confidence: 84%

Long‐term effects of immunotoxic cholinergic lesions in the septum on acquisition of the cone‐field task and noncognitive measures in rats

et al. 2006

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In rats, nonspecific mechanical or neurotoxic lesions of the septum impair spatial memory in, e.g., Morris water- and radial-maze tasks. Unfortunately, the lack of specificity of such lesions limits inferences about the role of the cholinergic hippocampal projections in spatial cognition. We therefore tested the effects of septal lesions produced by 192 IgG-saporin in rats, which is highly selective for basal forebrain cholinergic neurons, on home cage activity, noncognitive tests (modified Irwin test, open field and forced swimming tests, and various sensorimotor tasks), and the cone-field spatial learning task. The immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (-61%) and hippocampus (>-75%). Rats with lesions showed mild home-cage hyperactivity at 4 weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the cone-field task, rats with septal lesions made more working- and reference-memory errors than the controls, but acquisition curves were parallel in both groups. The speed of visiting cones was faster in the rats with lesions, indicative of disturbed attention or increased motivation. These data support the growing evidence that involvement of the septohippocampal cholinergic system in spatial learning and memory may have been overestimated in studies that used lesions with poor selectivity.

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“…Ethopropazine (0.3 mM; Sigma, St-Louis, MO) was used to block non-specific cholinesterases, and acetylthiocholine iodide (4 mM; Sigma, St. Louis, MO) was used as the substrate. The details of the following procedures have been described in our previous works [47,48].…”

Section: Tissue Preparationmentioning

confidence: 99%

“…Accumulation and electrically-evoked release of [ 3 H]-acetylcholine overflow was assessed as previously described [47,48]. Briefly, coronal slices (300 μm thick) of the dorsal hippocampus were prepared using a McIlwain tissue chopper (Model TC752, Mickle Laboratory Engineering Co. Ltd., UK).…”

Section: Accumulation Of [ 3 H]acetylcholine Overflowmentioning

confidence: 99%

Protective Effects of a synthetic glycosaminoglycan mimetic (OTR4132) in a rat immunotoxic lesion model of septohippocampal cholinergic degeneration

Pereira

Papy-García

Barritault³

et al. 2022

Glycoconj J

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Using a partial hippocampal cholinergic denervation model, we assessed the effects of the RGTA® named OTR4132, a synthetic heparan-mimetic biopolymer with neuroprotective/neurotrophic properties. Long-Evans male rats were injected with the cholinergic immunotoxin 192 IgG-saporin into the medial septum/diagonal band of Broca (0.37 µg); vehicle injections served as controls. Immediately after surgery, OTR4132 was injected into the lateral ventricles (0.25 µg/5 µl/rat) or intramuscularly (1.5 mg/kg). To determine whether OTR4132 reached the lesion site, some rats received intracerebroventricular (ICV) or intramuscular (I.M.) injections of fluorescent OTR4132. Rats were sacrificed at 4, 10, 20, or 60 days post-lesion (DPL). Fluorescein-labeled OTR4132 injected ICV or I.M. was found in the lesion from 4 to 20 DPL. Rats with partial hippocampal cholinergic denervation showed decreases in hippocampal acetylcholinesterase reaction products and in choline acetyltransferase-positive neurons in the medial septum. These lesions were the largest at 10 DPL and then remained stable until 60 DPL. Both hippocampal acetylcholinesterase reaction products and choline acetyltransferase-positive neurons in the medial septum effects were significantly attenuated in OTR4132-treated rats. These effects were not related to competition between OTR4132 and 192 IgG-saporin for the neurotrophin receptor P75 (p75NTR), as OTR4132 treatment did not alter the internalization of Cy3-labelled 192 IgG. OTR4132 was more efficient at reducing the acetylcholinesterase reaction products and choline acetyltransferase-positive neurons than a comparable heparin dose used as a comparator. Using the slice superfusion technique, we found that the lesion-induced decrease in muscarinic autoreceptor sensitivity was abolished by intramuscular OTR4132. After partial cholinergic damage, OTR4132 was able to concentrate at the brain lesion site possibly due to the disruption of the blood-brain barrier and to exert structural and functional effects that hold promises for neuroprotection/neurotrophism.

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Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75ntr receptors? a study using 192 IgG-saporin lesions in rats

Cited by 12 publications

References 36 publications

Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function

Comparative Study of Korean White, Red, and Black Ginseng Extract on Cholinesterase Inhibitory Activity and Cholinergic Function

Long‐term effects of immunotoxic cholinergic lesions in the septum on acquisition of the cone‐field task and noncognitive measures in rats

Protective Effects of a synthetic glycosaminoglycan mimetic (OTR4132) in a rat immunotoxic lesion model of septohippocampal cholinergic degeneration

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