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Improvements in memory after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis
Kong C, Shin J, Lee J, Koh C-S, Yoon M-S, Na Y, Chang J, Chang W (2017) Improvements in memory after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis. Neuroscience 2017 Abstracts 201.12 / C29. Society for Neuroscience, Washington, DC.
Summary: Abstract Introduction: Alzheimer’s disease is characterized pathologically by neurofibrillary tangles, amyloid plaques, gliosis, synaptic loss and cholinergic deficits. Recently, cell proliferation and neurogenesis was reported to have increased when the blood brain barrier (BBB) was disrupted by Focused ultrasound (FUS) with microbubbles. Previously, we have demonstrated that the cholinergic cell decreases in 192 IgG-saporin rat model, and that decrease in cholinergic cell is associated to decrease in cognitive behavior. The purpose of this study was to determine if the learning and memory abilities of the 192 IgG-saporin rat model are improved by FUS. Materials and Methods: Animals were divided into the four groups: Sham group (PBS injection), Lesion group (saporin injection), FUS-3 and FUS-10 groups (After 3 and 10 days after saporin injection, FUS treatment). Sprague-Dawley rats (200-250g) were injected bilaterally with 192 IgG-saporin into the ventricle. Rats were sonicated using a single-element transducer (frequency 0.5 MHz) with microbubble. The acoustic parameters used for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. To confirm cell proliferation, BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after FUS sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training for 5 days and the final test was performed. Results: In the water maze test, the FUS groups had a higher number of crossing times and staying time in the platform zone than the lesion group. Also, the FUS-3 group was higher than for the FUS-10 group. We confirmed that the amounts of DCX , NeuN , and BrdU were different between the FUS group and the lesion group. Conclusion: Our results suggest that FUS sonication facilitates recovery of memory and learning abilities in cholinergic deficits rat model. Moreover, the results suggest that neurogenesis is correlated with the mechanism of cognitive behavior recovery.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Basal forebrain cholinergic neurons are vital for cortical desynchronization and behavioral arousal observed after nicotine consumption
Sharma A, Sharma R, Mackey C, Sahota P, Thakkar M (2017) Basal forebrain cholinergic neurons are vital for cortical desynchronization and behavioral arousal observed after nicotine consumption. Neuroscience 2017 Abstracts 241.1 / LL2. Society for Neuroscience, Washington, DC.
Summary: Purpose: Nicotine is an addictive constituent of tobacco which severely affects behavior. Sleep disruptions including reducing total sleep time, increasing sleep fragmentation and reducing sleep efficiency are very common in nicotine users. However, the underlying neuronal mechanism of how nicotine promotes desynchronization and disrupts sleep is unknown. We have shown that the basal forebrain (BF) is a key brain region, mediating nicotine’s effects on sleep-wakefulness (SFN 2015; Poster#166). The BF contains multiple neuronal phenotypes including cholinergic, GABAergic and glutamatergic subtypes. Thus, this study was designed to examine the neuronal subtype responsible for nicotine effects on sleep-wakefulness. As a first step, we focused on BF cholinergic neurons because BF cholinergic neurons are wake-promoting, express nicotinic receptors and supply acetylcholine to the prefrontal cortex, hippocampus and amygdala. We hypothesized that lesions of BF cholinergic neurons will attenuate nicotine induced cortical arousal/desynchronization. Methods: To test our hypothesis, adult male Sprague-Dawley rats were implanted with sleep recording electrodes and were divided into two groups: Lesion: Selective lesion of the BF cholinergic neurons was performed by bilateral administration of immunotoxin, 192-IgG-Saporin (SAP; 0.28 µg/0.5µL/side) in the BF; Sham (controls): Rats were bilaterally infused with saline (0.5µL/side). After injections, animals were left undisturbed for 3 weeks. Day 1: saline was administered subcutaneously at light/sleep onset. Day 2: Nicotine (0.3 mg/Kg) was administered at the same time. Sleep- wakefulness was examined for next 6 hours. On completion, animals were euthanized and the brains were processed for choline acetyltransferase (ChAT) immunohistochemistry to verify BF cholinergic lesions. Results: Our preliminary results: As compared to controls, lesioned rats, with a 64% reduction in cholinergic neurons, displayed attenuated nicotine induced cortical desynchronization and behavioral arousal. Conclusions: Our results suggest that the BF cholinergic neurons mediate nicotine induced cortical arousal/desynchronization that may be the cause of sleep disruptions in nicotine users.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Glutamate and adenosine, basal forebrain and cortex: Cross-talk during prolonged wakefulness
Larin AA, Karpova SA, McCarley RW, Basheer R, Kalinchuk AV (2017) Glutamate and adenosine, basal forebrain and cortex: Cross-talk during prolonged wakefulness. Neuroscience 2017 Abstracts 72.2 /KK24. Society for Neuroscience, Washington, DC.
Summary: Recently we described a biochemical cascade which is critical in promoting recovery sleep (RS) after sleep deprivation (SD). It is initially triggered in the basal forebrain (BF) and later in the prefrontal cortex (PFC). This cascade includes production of inducible nitric oxide synthase (iNOS)-dependent NO followed by an increase in adenosine (AD). We hypothesized that iNOS induction is triggered by an increase in extracellular glutamate (Glu), and that the increase in AD prevents further rise in Glu via its inhibitory action on AD A1 receptor (A1R). To test this hypothesis, during 8h of SD, we first examined the time course of Glu and AD in BF/PFC. Further, to investigate the role of BF Glu receptors (GluRs) in this cascade, we measured the changes in BF/PFC AD and NREMs/delta after: a) stimulating BF GluRs by NMDA or AMPA without SD; b) blocking BF GluRs during SD by NMDAR or AMPAR selective antagonists. Finally, we measured Glu in the BF/PFC after blocking A1R. Furthermore, to determine the cellular target of glutamate effects, we examined the effects BF AMPA infusion on BF/PFC AD and NREMs/delta after BF cholinergic (ChBF) lesions using 192 IgG-saporin. Male rats were implanted with EEG/EMG recording electrodes and microdialysis guide cannulae targeting the BF and PFC. Microdialysis samples were collected during 8h SD and/or drug infusion. AD and Glu were measured using high performance liquid chromatography (HPLC) and ultra HPLC. To block NMDAR/AMPAR/A1R we used dizoclipine (MK-801)/6,7- dinitroquinoxaline-2,3-dione (DNQX)/8 cyclopentyltheophylline (CPT), respectively. 1) In the BF, Glu dramatically increased at the beginning of SD, followed by increase in AD at 2 h of SD. When AD maximized at 4 h of SD, Glu concurrently decreased to baseline. High AD levels were maintained till the end of SD. In the PFC, Glu significantly increased within 2h of SD. When AD increased at 5 h of SD, Glu returned to the baseline. 2) BF AMPA mimicked the effects of SD by increasing AD in both BF and PFC. NREMs/delta increased post AMPA-infusion. NMDA was not effective. 3) BF DNQX prevented AD increase during SD in BF/PFC and attenuated RS. MK-801 did not show any effect. 4) CPT Infusion to the BF/PFC induced dramatic increase in Glu till the end of SD. 5) Lesion of ChBF prevented BF/PFC AD increase during AMPA infusion and attenuated NREMs/delta post-infusion. A rapid increase in Glu during SD may be a trigger for the induction of iNOS-NO-AD cascade in both the BF and PFC. AD via A1R exerts a negative feedback on Glu neurotransmission, preventing its further rise and potential toxicity during long-term SD. The effect of Glu on SDinduced changes is primarily mediated via AMPAR, located on ChBF cells.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Increase in cortical endocannabinoid signaling in a rat model of basal forebrain cholinergic dysfunction
Llorente-ovejero A, Manuel I, Giralt MT, Rodríguez-puertas R (2017) Increase in cortical endocannabinoid signaling in a rat model of basal forebrain cholinergic dysfunction. Neuroscience 362:206-218.. doi: 10.1016/j.neuroscience.2017.08.008
Objective: To evaluate the eCB signaling in relation to the memory impairment induced in adult rats following a specific cholinergic lesion of the basal forebrain.
Summary: CB1 receptors present in presynaptic GABAergic terminals in the hippocampus are down regulated, but not those in cortical glutamatergic synapses.
Usage: 192-IgG-SAP was dissolved in aCSF under aseptic conditions to a final concentration of 130 ng/ml. aCSF or 192-IgG-SAP was bilaterally injected (1 ml/hemisphere) at a constant rate of 0.2 ml/min.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Acute effects of alcohol on sleep are mediated by components of homeostatic sleep regulatory system: An Editorial Highlight for ‘Lesions of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption’ on page 710.
Alam M, McGinty D (2017) Acute effects of alcohol on sleep are mediated by components of homeostatic sleep regulatory system: An Editorial Highlight for ‘Lesions of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption’ on page 710. J Neurochem 142(5):620-623.. doi: 10.1111/jnc.14100
Summary: In the study published in 2017, Sharma and colleagues report that the wake-promoting BF cholinergic neurons are critically involved in the acute alcohol-induced sleep promoting response and that extracellular adenosine buildup in the BF mediates this response. Using 192-IgG-SAP (Cat. #IT-01), they ablated BF cholinergic neurons unilaterally and compared extracellular adenosine levels on lesioned versus non-lesioned sides after local delivery of alcohol via reverse microdialysis. They found that adenosine levels were significantly lower (nearly 50%) on the side with a loss of cholinergic neurons.
Related Products: 192-IgG-SAP (Cat. #IT-01)
See Also:
Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption.
Sharma R, Sahota P, Thakkar M (2017) Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption. J Neurochem 142:710-720.. doi: 10.1111/jnc.14054
Summary: This project examined the sleep-promoting effect of alcohol and which neurons in the brain are involved in the process. 192-IgG-SAP (Cat. #IT-01; 0.3 µg/500 nL/side) was administered through bilateral basal forebrain infusions in rats. Based on the results, the authors suggest that alcohol promotes sleep by increasing extracellular adenosine via its action on cholinergic neurons of the basal forebrain.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion.
Lee S, Cho W, Lee Y, Han J (2018) Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol 55:3976-3989. doi: 10.1007/s12035-017-0620-5
Objective: Examine the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex.
Summary: The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer’s disease to stress since activation of NF-κB is associated with stress.
Usage: Male Sprague-Dawley rats received injections of 192 IgG-SAP dissolved in sterile 0.01 M PBS) at a concentration of 0.25 μg/μl.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Sigma-1 (σ1) receptor in memory and neurodegenerative diseases
Maurice T, Goguadze N (2017) Sigma-1 (σ1) receptor in memory and neurodegenerative diseases. Handb Exp Pharmacol 244:81-108. doi: 10.1007/164_2017_15
Related Products: 192-IgG-SAP (Cat. #IT-01)
Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.
Jeong D, Lee J, Chang W, Chang J (2017) Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze. BMC Neuroscience 18:29.. doi: 10.1186/s12868-017-0345-4
Summary: This study was performed to determine the stage of memory affected by medial septum deep brain stimulation (MS-DBS). Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.
Usage: Rats were injected bilaterally with 8 μl of 192-IgG-SAP (0.63 μg/μl) at the cerebroventricle.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Lipid mapping of the rat brain for models of disease.
Martínez-Gardeazabal J, González de San Román E, Moreno-Rodríguez M, Llorente-Ovejero A, Manuel I, Rodríguez-Puertas R (2017) Lipid mapping of the rat brain for models of disease. Biochim Biophys Acta Biomembr 1859:1548-1557.. doi: 10.1016/j.bbamem.2017.02.011
Objective: To map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment.
Summary: The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer’s disease.
Usage: 192 IgG-SAP in aCSF (135 ng/1 μl/hemisphere; 0.25 μl/min) was administered.
Related Products: 192-IgG-SAP (Cat. #IT-01)