sfn2002

Varga C, Grosche J, Brauer K, Seeger J, Harkany T, Hartig W (2002) Cholinergic neurons in the rabbit forebrain: Chemoarchitecture, in vivo labeling, immunolesions. Neuroscience 2002 Abstracts 35.3. Society for Neuroscience, Orlando, FL.

Summary: While the rabbit basal forebrain and its cholinergic components became useful targets for modeling of neuropathological changes associated with Alzheimer’s disease, their neuroanatomical organization is still largely elusive. Hence, we focused on (i) the number of cholinergic basal forebrain neurons (CBFN)in the major nuclei based on choline acetyltransferase (ChAT) immunoperoxidase labeling, (ii) the density of ChAT-immunoreactive fibers in distinct neocortical and hippocampal areas, (iii) mapping of projecting CBFN by low-affinity neurotrophin receptor p75 (p75NTR ) staining and (iv) the double fluorescence labeling of ChAT and the neuronal markers p75NTR, nitric oxide synthase (NOS), calbindin, calretinin, parvalbumin, tyrosine hydroxylase and substance P. While cholinergic interneurons were found in the hippocampus, they were not detectable in the neocortex. CBFN were shown to abundantly co-express p75NTR, except in the substantia innominata and ventral pallidum. Whereas cholinergic neurons were devoid of most investigated markers, a subset also contained calbindin or NOS. The selective in vivo labeling of CBFN was achieved with intracerebroventricularly (i.c.v.) injected carbocyanine 3-conjugated ME20.4IgG that recognizes an extracellular epitope of p75NTR. Parallel experiments revealed that the i.c.v. injection of ME20.4IgG-saporin conjugates led to the specific immunolesion of cholinergic cells in about one week, whereas long-term effects of the immunotoxin remain to be further elucidated.

Related Products: ME20.4-SAP (Cat. #IT-15)

Turchi JN, Saunders RC, Mishkin M (2002) Effects of cholinergic deafferentation of rhinal cortex on visual recognition in monkeys. Neuroscience 2002 Abstracts 82.5. Society for Neuroscience, Orlando, FL.

Summary: Excitotoxic lesions of the rhinal (perirhinal/entorhinal) cortices yield substantial deficits in visual recognition (Baxter and Murray, 2001; Malkova et al., 2001). To evaluate the mnemonic role of cholinergic inputs to this region, we compared the visual recognition performance of untreated monkeys with that of monkeys given rhinal cortex infusions of the selective cholinergic immunotoxin ME20.4-SAP. This toxin binds to the p75 receptor, borne by corticopetal cholinergic neurons of the basal forebrain, and is retrogradely transported to the cell body where it permanently destroys ribosomal function. Both groups were first trained to criterion in the rule for delayed nonmatching-to-sample (DNMS) with trial-unique stimuli at a 10-s delay in a Wisconsin General Testing Apparatus. This was followed by treatment and recovery for the experimental group (n=3) and an equivalent rest period for the control group (n=4), after which both groups were retrained on the DNMS rule and then given a memory performance test with increasing delays (30, 60, and 120 s) and list lengths (3, 5, 10, and 20 stimuli). The experimental group relearned the DNMS rule without significant impairment but then demonstrated robust deficits when tested with increasing delays (a mean of 83% vs 95% for controls) and list lengths (67% vs 86% for controls). The findings complement results obtained in a study of muscarinic receptor blockade in the perirhinal cortex (Tang et al., 1997) and indicate that cholinergic integrity of the rhinal cortex is critical for visual recognition memory.

Related Products: ME20.4-SAP (Cat. #IT-15)

Mohapel P, Leanza G, Lindvall O (2002) Alterations in forebrain acetylcholine influence hippocampal neurogenesis in the adult rodent. Neuroscience 2002 Abstracts 23.9. Society for Neuroscience, Orlando, FL.

Summary: Little is known about how various experiential, environmental and pathological factors regulate neurogenesis in the adult hippocampus. Since the hippocampus receives abundant cholinergic innervation and contains some of the densest distributions of acetylcholine (ACh) fibers, we investigated its potential role in adult neurogenesis. Adult rats received multiple bromodeoxyuridine (BrdU) injections 3 weeks following lesions of the adult rodent forebrain cholinergic projections by intracerebroventricular infusions of 192 IgG-saporin. The day following BrdU administration we observed a significant 20% to 30 % decrease in proliferation in the subgranular cell layer of the dentate gyrus with ACh lesioning. This decrease persisted through to 4 weeks after BrdU administration, when most proliferated cells co-expressed neuronal markers. Conversely, in a separate experiment, naive rats receiving simultaneous injections of the ACh agonist physostigmine and BrdU demonstrated a 30 % increase in proliferated cells (1 day later) and neurons (4 weeks later) in the subgranular cell layer. Our data indicate that cholinergic mechanisms in the forebrain are involved in the regulation of neurogenesis and that this effect may be indirect or direct in the hippocampus.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Zambon NJ, Liberatore MA, Nagle RA, Pokala VN, Li P, Johnson DA (2002) Steroid sulfatse inhibition potentiates working memory deficit induced by 192 IgG-saporin. Neuroscience 2002 Abstracts 82.6. Society for Neuroscience, Orlando, FL.

Summary: Infusion of 192 IgG-saporin (SAP) into the medial septum (MS) of rats selectively lesions cholinergic neurons and impairs acquisition of a delayed matching to position T-maze task. Since steroid sulfatase inhibitors allosterically inhibit the GABA-A receptor and enhance cognition, the present study investigated the cognitive effects of sulfatase inhibition on SAP lesioned animals. Male Sprague-Dawley rats received intraseptal infusions of either cerebrospinal fluid (CSF) or 0.22 μg/μl SAP. Eight days after the infusion, the rats were given an IP injection of either the steroid sulfatase inhibitor DU-14 (30mg/ml) or vehicle daily for 14 days, then every other day during the testing period. In the acquisition phase of testing, each rat completed 8 trial pairs per day until reaching criterion (15 of 16 correct choices). The rats were then tested for retention of the task by inserting delays of 10, 20, and 30 seconds after the first trial of a pair. DU-14 potentiated the impairment in acquisition produced by SAP. The introduction of a delay resulted in deceased performance in all treatment groups except rats administered DU-14 without SAP lesioning. These results suggest that DU-14 may enhance cognition in cholinergically intact animals, but the combination of DU-14, with cholinergic lesioning of MS, impairs working memory by inhibition of both cholinergic and GABAergic neurotransmission.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Pokala VN, Libertore MA, Zambon NJ, Nagle RA, Li PK, Witt-Enderby PA, Johnson DA (2002) Effect of 192 IgG-saporin medial-septum lesion on hippocampal receptor density in rats. Neuroscience 2002 Abstracts 82.7. Society for Neuroscience, Orlando, FL.

Summary: The aim of the study was to quantify the effect of selective cholinergic neurotoxin192 IgG-saporin (SAP) medial septal (MS), lesions on hippocampal muscarinic, GABAA and NMDA receptor density. Rats were injected with SAP (0.22 and 0.45 μg/μl) into the MS. After 6 weeks, hippocampal tissue was collected and saturation radioligand binding assays were performed to determine the receptor density. 3H-QNB was a muscarinic antagonist, 3H-muscimol a GABAergic agonist and 3H-MK-801 an NMDA antagonist were utilized. The results demonstrated a dose dependent increase in muscarinic receptor density (B-max) of 226 and 355% respectively. These results suggest changes in receptor density in response to hippocampal cholinergic denervation.

Related Products: 192-IgG-SAP (Cat. #IT-01)