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Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation.
Hulsey D, Hays S, Khodaparast N, Ruiz A, Das P, Rennaker R, Kilgard M (2016) Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimul 9:174-181. doi: 10.1016/j.brs.2015.12.007
Summary: Recent work has suggested that vagus nerve stimulation (VNS) can enhance neuroplasticity, and coupled with other training can drive motor cortex reorganization. These findings highlight the potential of VNS to support recovery from neurological disease. Pretrained rats received bilateral injections totaling 3.75 μg of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis (NB). Mouse-IgG-SAP (Cat. #IT-18) was used as control. Control animals displayed a substantial increase in proximal limb representation, lesion of the NB prevented this increase. Motor performance was similar between lesion and control groups, indicating that the difference in representation was not due to altered limb function.
Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)
Basal forebrain cholinergic deficits reduce glucose metabolism and function of cholinergic and gabaergic systems in the cingulate cortex.
Jeong D, Oh J, Lee J, Lee J, Cho Z, Chang J, Chang W (2016) Basal forebrain cholinergic deficits reduce glucose metabolism and function of cholinergic and gabaergic systems in the cingulate cortex. Yonsei Med J 57:165-172. doi: 10.3349/ymj.2016.57.1.165
Summary: A common result of cholinergic neuron loss in the hippocampus and cortical regions due to Alzheimer’s disease is a reduction in glucose metabolism. The authors examine the interaction between the cell loss and metabolic changes. Rats received 5-μg bilateral cortical injections of 192-IgG-SAP (Cat. #IT-01), were subject to water maze testing, and analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Lesioned animals displayed decreased learning performance and reduced metabolic activity in the cingulate cortex.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Perinatal 192 IgG-saporin as neuroteratogen.
Petrosini L, De Bartolo P, Cutuli D, Gelfo F (2016) Perinatal 192 IgG-saporin as neuroteratogen. Curr Top Behav Neurosci 29:111-123. doi: 10.1007/7854_2015_418
Summary: The authors discuss the effects of perinatal administration of 192-IgG-SAP (Cat. #IT-01) and areas of research that have been investigated through the use of these lesions. The chapter covers a description of 192-IgG-SAP, lesioning methods, and outlines the short- and long-term biochemical, structural, behavioral, and cognitive effects of 192-IgG-SAP administration.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Treatment efficacy of NGF nanoparticles combining neural stem cell transplantation on Alzheimer’s Disease model rats.
Chen Y, Pan C, Xuan A, Xu L, Bao G, Liu F, Fang J, Long D (2015) Treatment efficacy of NGF nanoparticles combining neural stem cell transplantation on Alzheimer’s Disease model rats. Med Sci Monit 21:3608-3615. doi: 10.12659/msm.894567
Summary: NSC (neural stem cell) transplants into animals have been shown to compensate for the loss of cholinergic cells in the basal forebrain, a hallmark of Alzheimer’s disease. One hurdle to overcome is the actuation of NSC differentiation into the specific replacement cells needed. NGF has been shown to induce this differentiation, but it has a very short half-life and does not permeate tissue very effectively. In this work the authors administered 5 mcl of icv 192-IgG-SAP (Cat. #IT-01) to rats, followed by a graft of NCSs in the presence of NGF nanoparticles with a polymer coating. Rats receiving both NCSs and NGF nanoparticles showed significantly improved memory and learning functions as compared to control animals.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cognitive and motor deficits in a rodent model of Parkinson’s disease displaying concurrent dopamine and acetylcholine loss
Ostock CY, Conti MM, Larose T, Meadows S, Bishop C (2015) Cognitive and motor deficits in a rodent model of Parkinson’s disease displaying concurrent dopamine and acetylcholine loss. Neuroscience 2015 Abstracts 676.26/D33. Society for Neuroscience, Chicago IL.
Summary: Dopamine (DA) loss in Parkinson’s disease (PD) is frequently accompanied by degeneration of acetylcholine neurons within the basal forebrain (BF) and the pedunculopontine nucleus (PPN). Recently, Ach neurons in these nuclei have been implicated in both the motor and non-motor symptoms of PD. However, few rodent models of PD actually account for Ach loss in both the BF and PPN. Here, we evaluated the effects of concurrent BF and PPN Ach loss alone and in combination with striatal DA loss on motor and cognitive performance in a rat model of PD. Sprague-Dawley rats (N = 44) received bilateral: striatal 6-OHDA lesions to deplete DA (DA-lesioned; n = 14), BF (192 IgG-Saporin) and PPN (anti-ChAT Saporin) saporin lesions to deplete Ach (Ach-lesioned; n = 10), combined 6-OHDA + saporin lesions (dual-lesioned; n = 6) , or sham lesions (n = 14). Following recovery from surgery, rats underwent a battery of motor and cognitive behavioral tests. Results indicated that Ach-lesioned and dual-lesioned rats displayed spatial memory deficits on the Morris Water Maze and Spontaneous Alternation tests. DA and Ach lesions alone impaired stepping for the forepaw adjusting steps and vibrissae-elicited paw placement tests and this deficit was exacerbated in dual-lesioned rats. However, only rats with Ach or dual lesions showed motor deficits on the rotarod tests. Collectively, these findings demonstrate that Ach loss may exacerbate cognitive and motor symptoms in PD and highlight the importance of including Ach loss in preclinical models of PD.
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-ChAT-SAP (Cat. #IT-42), Saporin (Cat. #PR-01)
Neuroprotective effects of placenta-derived mesenchymal stem cell for rat model of dementia
Lee J, Jeong D, Chang W, Chang J (2015) Neuroprotective effects of placenta-derived mesenchymal stem cell for rat model of dementia. Neuroscience 2015 Abstracts 626.12/AA3. Society for Neuroscience, Chicago IL.
Summary: Introduction: The neuroprotective effects of mesenchymal stem cell (MSC) in neurodegenerative disease have been recently reported. In contrast of the transplantation effect of MSC derived from bone marrow, adipose tissue and human umbilical cord blood, the study of placenta-derived mesenchymal stem cell (pMSC) is still little known. In this study, we studied the effective method of placenta-derived mesenchymal stem cell (pMSC) transplantation by comparing intracerebroventrical (icv) with intravenous (iv) injection. In addition, we also tried to compare the effect of pMSC transplantation and standard treatment for dementia. Materials and Methods: We used the rat model of dementia by damaging basal forebrain cholinergic neurons using 192 IgG-saporin. 1 week after administration of 192 IgG-saporin, pMSC was injected via intraventricular route (icv, 1.2 x 106 cells/ul) or intravenous route (iv, 5 x 106 cells/200 ul) and Cyclosporine (immunosuppressant drug) were administrated at peritoneal cavity for preventing immune reaction by innate immunity (daily / 5 weeks). To compare the effect of stem cell therapy and standard therapy, some rats were treated with donepezil and 5 weeks after transplantation, all animals were tested visuo-spatial cognitive functions by Morris water maze. Results: The probe test of water maze, performance of pMSC transplantation group and donepezil group increased time spent in target quadrant and in platform zone. Also acetylcholinesterase(AChE) activity was increased in the hippocampus and medial prefrontal cortex(mPFC). Interestingly, iv group showed more improved behavior performance and acetylcholinesterase(AChE) activity than icv group. Immunohistochemistry of stem121 marker of stem cell and iba1 maker of microglia and Western blot of DCX and BDNF were also suggested the beneficial effect of both stem cell therapy and standard donepezil treatment. Conclusions: Our result show that pMSC recover spatial memory of dementia model by increasing acetylcholinesterase(AChE) activity. Intravenous injection of pMSC seemed to be more beneficial route for both risk managing and symptom improvement. And pMSC transplantation also showed similar efficacy of the donepezil for improving cognitive function. For determining the superiority of both treatment, further investigation should be needed. Acknowledgements: This work was supported (YonseiChallenge) by the Yonsei University Future-leading Research Initiative of 2014 and CABMC (Control of Animal Brain using MEMS Chip) funded by Defense Acquisition Program Administration (UD140069ID).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Compensatory cortical sprouting across the lifespan of the rat
Carnes B, DeLacalle S (2015) Compensatory cortical sprouting across the lifespan of the rat. Neuroscience 2015 Abstracts 391.10/C34. Society for Neuroscience, Chicago IL.
Summary: To investigate the plastic capacity of the cholinergic system in a partial animal model of Alzheimer’s disease, adult and aged rats received unilateral lesions of the horizontal diagonal band of Broca (HDB) using the cholinergic-specific toxin 192-IgG-saporin. The rats were sacrificed at 2, 4, 8, 12, or 24 weeks post lesion. Immuno- and histochemical techniques were used to quantify the effects of the lesion. Tissues were stained using an acetylcholinesterase technique. A 230µm by 200µm grid was used to indirectly measure the density of cholinergic fibers in the Entorhinal Cortex (EC). We compared our data to a young (3 month old) control group (Hartonian, 2005) in which the maximal loss of fiber density occurred by 8 weeks post-lesion and recovered to 75% of the intact contralateral EC by 12 weeks. All groups (young adult: 12-15; adult: 18; aged: 24-27 month old rats at the start of the experiment) exhibited a decrease in cortical fiber density after the lesion, which was more pronounced in the young adult group. All groups showed a recovery in fiber density to 60-80% of the intact side by 24 weeks post lesion. Interestingly, the loss occurred faster and more intense in the young adult group (to 25% of the intact side at 8 weeks post-lesion) than in the older ones (to 60% of the intact side by week 12 post lesion). Twenty four weeks after the lesion, the young adult group had recovered fiber density to 70%. The adult group also reached 70%, and the aged group reached 80% of the contralateral intact side. We conclude that following a cholinergic specific lesion, a compensatory mechanism is activated in the basal forebrain such that surviving neurons, projecting to the same target, are able to extend terminals and occupy the denervated area. It remains to be investigated whether the sprouts are able to establish proper synaptic connections and make a functional recovery.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Basal forebrain cholinergic lesions attenuate the reinstatement of cocaine-seeking produced by a discriminative stimulus in goal-trackers but not sign-trackers
Jones JL, Pitchers KK, Robinson TE, Sarter M (2015) Basal forebrain cholinergic lesions attenuate the reinstatement of cocaine-seeking produced by a discriminative stimulus in goal-trackers but not sign-trackers. Neuroscience 2015 Abstracts 411.15/L-15. Society for Neuroscience, Chicago IL.
Summary: Goal-trackers (GTs), compared to sign-trackers (STs), express higher levels of acetylcholine when performing a cue detection and processing task. We hypothesized, therefore, that GTs utilize their basal forebrain cholinergic systems differently and to a greater extent than STs, such that this system may be critical for signal-induced behavior in GTs but not STs. The purpose of this experiment was to investigate individual variation in the reinstatement of drug-seeking behavior produced by a signal indicating cocaine availability (a discriminative stimulus), as well as the influence of the basal forebrain cholinergic system. STs and GTs were trained to self-administer cocaine using an intermittent access (IntA) procedure. The IntA procedure involved allowing animals access to cocaine for discrete 5-min drug available periods indicated by a light signal (DS+) separated by 25-min no drug available periods indicated by a different signal (DS-) in a different location than the DS+. This procedure results in ‘spiking’ brain levels of cocaine. Once stable performance was achieved on this procedure, animals underwent extinction training where the context remained similar to the IntA procedure but was now devoid of both DSs and an active response no longer had any consequence. STs and GTs did not differ in the acquisition or expression of self-administration or extinction training. After behavior was stably extinguished, half of the subjects received bilateral infusions of the cholinotoxic immunotoxin 192 IgG-saporin into the basal forebrain, while the other half received sham surgeries. Animals underwent 5 days of re-extinction. Finally, they underwent a reinstatement test during which the DS+ was presented non-contingently for 2 sec on a variable time schedule. Current results show that the ST-lesion group and both sham groups reinstated responding upon exposure to the DS+, compared to the last day of extinction. In contrast, the GT-lesion group did not reinstate responding, relative to the last day of extinction and, additionally, showed fewer active responses during the reinstatement test than the GT-sham group. Our findings suggest that the basal forebrain cholinergic system is involved in the reinstatement of drug-seeking behavior produced by a signal indicating drug availability in some animals (GTs), but not others (STs), further supporting the notion that drug cues are processed very differently in STs and GTs.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic contributions to PASA and functional compensation in rats
Yegla B, Francesconi JA, Forde JC, Parikh V (2015) Cholinergic contributions to PASA and functional compensation in rats. Neuroscience 2015 Abstracts 253.11/V29. Society for Neuroscience, Chicago IL.
Summary: Neuroimaging studies have indicated increased recruitment of prefrontal regions coupled to reduced activation of posterior regions in task-performing older adults. This shift of activity in cortical networks is described as posterior-anterior shift in aging (PASA). What cellular mechanisms contribute to PASA and how it provides functional compensation for age-related decline in cognitive capacities remains unknown? Cortically-projecting forebrain cholinergic neurons modulate cortical networks and facilitate attentional processes. Here we examined whether cortical cholinergic inputs contribute to PASA expression and maintenance of attentional capacities in aging. Young (3 months) and aged (24 months) Wistar rats were trained in a sustained attention task (SAT) that requires them to distinguish between signal and non-signal events. After attaining criterion performance (_70% correct responses for 3 consecutive sessions), rats received bilateral infusions of cholinoselective immunotoxin 192-IgG SAP either into the prefrontal cortex (PFC) or posterior parietal cortex (PPC) to produce partial cholinergic deafferentation. Control animals were infused with saline. Following behavioral testing 4 weeks post-surgery, animals were perfused 45-min after the last session to examine changes in neuronal activity in the PFC and PPC using c-fos immunohistochemistry. Partial prefrontal cholinergic deafferentation in aged rats produced robust deficits in response accuracy on signal trials as compared to aged sham (p=0.04) and young lesion (p=0.03) rats. In general, c-fos expressing neurons were higher in the PFC of aged rats as compared to young rats. Although prefrontal neuronal activity did not differ between the aged sham and PFC lesion group, there was a trend for a higher neuronal activity in the PPC of the latter. Surprisingly, attentional performance displayed a negative correlation with the prefrontal activity. Neuronal activity in the PPC did not correlate with performance. PPC-infused aged rats displayed no lesion effect on SAT and performed better than aged rats infused with 192 IgG-SAP into the PFC (p=0.04). Moreover, partial loss of cholinergic inputs into the PPC reduced PFC recruitment as compared to PFC lesioned aged rats. Collectively, these data suggest that reduced cortical activity in young rats compared to aged rats may represent better neural capacity, or the efficient utilization of normal brain regions, for task performance. Moreover, PASA is not triggered by prefrontal cholinergic inputs, but these inputs may regulate the reciprocal interactions between the PFC and PPC networks to maintain optimal performance in aging.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Preliminary investigation on the antidepressive effect of chronic oxotremorine treatment in a rodent model of Alzheimer’s disease
Nair DV, Al-Badri MM, Peng H, Pachego-Quinto J, Eckman CB, Iacono D, Eckman EA (2015) Preliminary investigation on the antidepressive effect of chronic oxotremorine treatment in a rodent model of Alzheimer’s disease. Neuroscience 2015 Abstracts 40.29/C34. Society for Neuroscience, Chicago IL.
Summary: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the rate of progression varies from individual to individual. A great deal of evidence supports the idea that depression and other neuropsychiatric conditions co-exist with cognitive decline. However, the neurobiological basis of these symptoms and their influence on the clinical course of AD remain unclear. Our lab has shown previously that the 192-IgG saporin rat model of AD-like basal forebrain cholinergic cell loss exhibits a depression-like phenotype that develops months after the well-described impairment in spatial working memory. Furthermore, we have shown that chronic intracerebroventricular administration of the muscarinic agonist oxotremorine reverses both spatial working memory deficits and the depression-like behavior triggered by cholinergic denervation, and induces hippocampal neurogenesis. Current experiments are focused on determining additional pathological correlates of depression in this model and how they may be modulated by muscarinic agonists. To induce AD-like basal forebrain cholinergic cell loss, adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP) or saline as control (SHAM). After a 5 week recovery period, the rats received either 2 or 6 weeks of icv infusion of either oxotremorine or vehicle (saline) via osmotic minipump. Behavioral testing to assess the depressive phenotype was carried out using the sucrose consumption test every 2 weeks during oxotremorine treatment. The phenotype was further confirmed by forced swim test. The levels of ChAT, tryptophan hydroxylase (TPH), muscarinic receptors and FosB and ΔFosB were assessed in the hippocampus, basal forebrain, and orbitofrontal cortex by western blot and immunohistochemistry. Our preliminary results show increases in TPH, M1 receptors and FosB in the hippocampus, basal forebrain, and orbitofrontal cortex of a subset of treated animals, but no changes ChAT or ΔFosB. Further experiments are in progress to determine if there are changes in the expression of these and additional proteins in other brain regions including the nucleus accumbens, an area involved in activational aspects of motivation which also contributes to behavioral disorders such as to depression. The results of these studies may provide new insight in understanding the molecular basis of depression and antidepressant action of oxotremorine thereby defining new targets for possible therapeutic intervention for depressive symptoms in AD.
Related Products: 192-IgG-SAP (Cat. #IT-01)