Targeting Topics 04q4

Decreased neurogenesis after cholinergic forebrain lesion in the adult rat.

Cooper-Kuhn CM, Winkler J, Kuhn HG.

J Neurosci Res 77(2):155-165, 2004.

Adult mammalian brains can produce new neurons, mainly in two areas: the interconnected system of the lateral ventricle and the olfactory bulb, and the dentate gyrus of the hippocampus. The authors used a 3.5 µg-injection of 192-Saporin (Cat. #IT-01) into the right ventricle of rats to determine whether cholinergic input is necessary for adult neurogenesis. The results suggest that acetylcholine, a product of cholinergic neurons, is necessary for the survival of newly-formed neurons.

Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation.

Gil-Bea FJ, Dominguez J, Garcia-Alloza M, Marcos B, Lasheras B, Ramirez MJ.

Neuropharmacology 47(2):225-232, 2004.

Previous studies from this group demonstrated that 5-HT(3) receptor antagonists potentiated by GABA(A) antagonists increased acetylcholine (ACh) release in the rat cerebral cortex. This series of experiments investigated the effects of these antagonists on rats with 0.067 µg-bilateral infusions of 192-Saporin (Cat. #IT-01) into the nucleus basalis magnocellularis. Even after lesioning with 192-Saporin, rats treated with the 5-HT(3) and GABA(A) receptor antagonists displayed increased ACh release, indicating that these antagonists may have use as treatments for cognitive disorders.

Habituation to stress and dexamethasone suppression in rats with selective basal forebrain cholinergic lesions.

Helm KA, Ziegler DR, Gallagher M.

Hippocampus 14(5):628-635, 2004.

Basal forebrain cholinergic neurons may be involved in hippocampal and medial prefrontal cortex inhibition of glucocorticoid stress responses. The authors investigated the effects of 0.05 to 0.075 µg injections of 192-Saporin (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band of rats by measuring corticosterone levels during a restraint stress test. Lesioned rats displayed less stress suppression on the administration of dexamethasone than controls, indicating that cholinergic neurons are involved in these stress responses.

Hindbrain catecholamine neurons mediate consummatory responses to glucoprivation.

Hudson B, Ritter S.

Physiol Behav 82(2-3):241-250, 2004.

Norepinephrine (NE) and epinephrine (E) neurons appear to potently stimulate feeding behavior when administered to the hypothalamus. Previous work has indicated that these neurons play important roles in feeding responses due to glucoprivation. Bilateral 42 ng-injections of anti-DBH-SAP (Cat. #IT-03) were administered to rats to investigate the roles of NE and E neurons in the consummatory phase of the glucoprivic response. The results indicate that catecholaminergic neurons are involved in both appetitive and consummatory responses to glucoprivation.

Minocycline protects basal forebrain cholinergic neurons from mu p75-saporin immunotoxic lesioning.

Hunter CL, Quintero EM, Gilstrap L, Bhat NR, Granholm AC.

Eur J Neurosci 19(12):3305-3316, 2004.

In Alzheimer’s disease basal cholinergic degeneration is accompanied by glial activation and the release of pro-inflammatory cytokines. To investigate whether neural events other than degeneration can cause effects of Alzheimer’s disease, the authors treated mice with minocycline after lesioning the basal forebrain with 3.6 µg of mu p75-SAP (Cat. #IT-16). Administration of minocycline reduced the loss of cholinergic neurons, reduced glial response to the lesion, and lessened the cognitive impairment due to mu p75-SAP lesions.

Recurrent paraplegia after remyelination of the spinal cord.

Jasmin L, Ohara PT.

J Neurosci Res 77(2):277-284, 2004.

Previously, the authors demonstrated that a 3 µg-injection of CTB-SAP (Cat. #IT-14) into the lumbosacral intrathecal space caused a loss of motor function due to spinal demyelination. The motor function was recovered and stable for up to 9 months, after which the rats exhibited a slow deterioration of motor function, loss of spinal white matter, and the appearance of calcium deposits. The results indicate that the CTB-SAP-induced demyelination model is useful for investigating long term effects of axon and motoneuron loss.

Sound sequence discrimination learning is dependent on cholinergic inputs to the rat auditory cortex.

Kudoh M, Seki K, Shibuki K.

Neurosci Res 50(1):113-123, 2004.

The auditory cortex (AC) is thought to play a role in the discrimination of sound sequences. The authors investigated the role of cholinergic inputs to the AC in processing these sequences by injecting 5 µg of 192-Saporin (Cat. #IT-01) into either the lateral ventricle or bilateral AC of rats. Treated animals displayed suppressed sound discrimination learning, but discrimination between two sound components was unaffected. The results suggest that cholinergic neurons in the AC are highly involved in sound sequence learning.

The effects of cerebellar damage on maze learning in animals.

Lalonde R, Strazielle C.

Cerebellum 2(4):300-309, 2003.

Traditionally the cerebellum has been associated with motor control, but recent work has suggested that it plays a role in cognitive functions such as spatial learning as well. This study discusses the effects of cerebellar mutations in mice, and OX7-SAP (Cat. #IT-02) lesions in rats on water maze learning models. Results indicate that the cerebellum plays a role in working memory and the procedural aspect of maze learning, as well as being an important element of motor control.

Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity.

Mattsson A, Pernold K, Ogren SO, Olson L.

Neuroscience 127(3):579-591, 2004.

The authors have recently shown that cholinergic denervation of the basal forebrain in rats leads to an increased motor response to d-amphetamine, a hallmark of schizophrenia. In the present study 192-Saporin (Cat. #IT-01) was injected into the nucleus basalis magnocellularis or the medial septum/diagonal band of Broca, and OX7-SAP (Cat. #IT-02) was injected intracerebroventricularly. The dopaminergic hyper-reactivity was induced by lesions to the cortex cerebri, but not by damage to the cerebellum or hippocampus.

Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats.

Ricceri L, Minghetti L, Moles A, Popoli P, Confaloni A, De Simone R, Piscopo P, Scattoni ML, di Luca M, Calamandrei G.

Exp Neurol 189(1):162-172, 2004.

A distinctive feature of Alzheimer’s disease is the loss of cholinergic neurons in the basal forebrain (BF). The authors investigated long-term effects of BF cholinergic lesions on several parameters. Administration of 0.21 µg of 192-Saporin (Cat. #IT-01) to the third ventricle of 7 day-old rats was followed by an evaluation of protein levels and cortical EEG patterns at 6 months of age. The findings indicate that permanent neonatal BF cholinergic damage may provide a model for abnormal adult cholinergic function.

NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius.

Wang G, Anrather J, Huang J, Speth RC, Pickel VM, Iadecola C.

J Neurosci 24(24):5516-5524, 2004.

Using immunoelectron microscopy the authors investigated whether NADPH oxidase is involved in angiotensin II signaling in central autonomic neurons of rat. Angiotensin type 1 receptor (AT-1r)-expressing neurons were identified with an AT-1r antibody (Cat. #AB-N27AP) from which AT-1Ar (AB-N25AP) and AT-1Br (AB-N26AP) are affinity purified. Colocalization of AT-1r’s and a NADPH oxidase subunit provides evidence that NADPH oxidase is involved in the effects of angiotensin II on autonomic neurons.

Selective lesioning of the cholinergic septo-hippocampal pathway does not disrupt spatial short-term memory: a comparison with the effects of fimbria-fornix lesions.

Winters BD, Dunnett SB.

Behav Neurosci 118(3):546-562, 2004.

The authors wished to investigate the role of the cholinergic system of the basal forebrain in delayed matching (DMTP)- and nonmatching (DNMTP)-to-position tasks after bilateral injections of 0.035 µg of 192-Saporin (Cat. #IT-01) into the dorsal and ventral hippocampus. The treated animals were compared to rats given fimbria-fornix (FF) lesions. Only the FF-lesioned animals showed impairment on DMTP and DNMTP tasks, demonstrating that the cholinergic septohippocampal system is not required for successful DMTP or DNMTP performance.

Age-dependent effect of cholinergic lesion on dendritic morphology in rat frontal cortex.

Works SJ, Wilson RE, Wellman CL.

Neurobiol Aging 25(7):963-974, 2004.

Aged rats display more dramatic and longer lasting effects due to brain injury than young animals. The authors examined the role cholinergic neurons may play in brain plasticity after injury in rats of varying ages. 0.15 µg of 192-Saporin (Cat. #IT-01) was injected into the nucleus basalis magnocellularis of young, middle-aged, and aged rats. Some types of injury were only seen in middle-aged and aged rats, and changes in dendritic morphology were least marked in the young animals.