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Examination of zinc in the circadian system.
Moshirpour M, Nakashima AS, Sehn N, Smith VM, Thackray SE, Dyck RH, Antle MC (2020) Examination of zinc in the circadian system. Neuroscience 432:15-29. doi: 10.1016/j.neuroscience.2020.02.016 PMID: 32087262
Objective: To examine the anatomical and functional aspects of zinc in the circadian system.
Summary: Neither enhancement nor chelation of free zinc at either the SCN or IGL altered circadian responses to phase-shifting light in hamsters.
Usage: Retinal immunohistochemistry (1:5000) included a 20-min wash in 4% PFA prior to initiation of the IHC protocol.
Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)
More than scratching the surface: recent progress in brain mechanisms underlying itch and scratch.
Liu X, Miao XH, Liu T (2020) More than scratching the surface: recent progress in brain mechanisms underlying itch and scratch. Neurosci Bull 36(1):85-88. doi: 10.1007/s12264-019-00352-1
Summary: The discovery of descending neural circuitry to drive the itch-scratching cycle may provide potential therapeutic targets in the central nervous system for the management of chronic itch.
Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Blank-SAP (400 ng/5 mL).
Related Products: Bombesin-SAP (Cat. #IT-40)
Time and region-dependent manner of increased brain derived neurotrophic factor and TrkB in rat brain after binge-like methamphetamine exposure
Moreira da Silva Santos A, Gorman AM, Kelly JP, Doyle KM (2020) Time and region-dependent manner of increased brain derived neurotrophic factor and TrkB in rat brain after binge-like methamphetamine exposure. Neurosci Lett 715:134606. doi: 10.1016/j.neulet.2019.134606 PMID: 31693929
Objective: To investigate the effect of binge-like methamphetamine (MA) dosing on brain-derived neurotrophic factor (BDNF) levels and its receptors, trkB and p75NTR.
Summary: The binge-like regimen of MA affects expression of BDNF and its receptors, particularly the trkB receptor, in a time and region dependent manner, and highlights the importance of the frontal cortex and the striatum in the response following MA binge-like dosing.
Usage: Western blot (1:1000) NGFr (mu p75) Rabbit Polyclonal, affinity-purified
Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)
Contribution of the retrotrapezoid nucleus and carotid bodies to hypercapnia- and hypoxia-induced arousal from sleep.
Souza GMPR, Stornetta RL, Stornetta DS, Abbott SBG, Guyenet PG (2019) Contribution of the retrotrapezoid nucleus and carotid bodies to hypercapnia- and hypoxia-induced arousal from sleep. J Neurosci 39(49):9725-9737. doi: 10.1523/JNEUROSCI.1268-19.2019
Objective: To examine the contribution of two lower brainstem nuclei that could be implicated in CO2 and hypoxia-induced arousal.
Summary: RTN, a brainstem nucleus that mediates the effect of brain acidification on breathing, also contributes to arousal elicited by CO2 but not hypoxia.
Usage: To ablate the retrotrapezoid nucleus (RTN), SSP-SAP was administered (2.4 ng) through bilateral injections via a dorsal craniotomy.
Related Products: SSP-SAP (Cat. #IT-11)
Corticolimbic stress regulatory circuits, hypothalamo–pituitary–adrenocortical adaptation, and resilience
Herman JP (2020) Corticolimbic stress regulatory circuits, hypothalamo–pituitary–adrenocortical adaptation, and resilience. Chen A (Ed.): Stress Resilience 291-309. Academic Press doi: 10.1016/B978-0-12-813983-7.00019-7
Summary: Review. Immunolesion of paraventricular nucleus (PVN)-projecting norepinephrine (NE) neurons with Anti-DBH-SAP attenuates acute stress reactivity (interestingly, to restraint), but it does not inhibit somatic or HPA axis responses to stress in any simple way (Flak et al.). PVN-projecting NE neurons appear to be responsible for acute responses to systemic stressors, but they do not appear to be important in mediating effects of chronic stress (Ritter et al.).
Usage: Flak et al. injected 8.82 ng of Anti-DBH-SAP into the PVN. Ritter et al. injected 42 ng into the PVN.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
See Also:
- Flak J et al. Role of paraventricular nucleus-projecting norepinephrine/epinephrine neurons in acute and chronic stress. Eur J Neurosci 39:1903-1911, 2014.
- Ritter S et al. Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology 144(4):1357-1367, 2003.
Effect of medial septal selective and non selective lesions on exploratory behavior and recognition memory
Kruashvili L, Beselia G, Chkhikvishvili N (2019) Effect of medial septal selective and non selective lesions on exploratory behavior and recognition memory. Neuroscience 2019 Abstracts 336.01. Society for Neuroscience, Chicago, IL.
Summary: Investigation of cholinergic system and memory interaction has especially become the object of scientific attention due to the clinical and experimental data, in which the severity of dementia in Alzheimer’s disease (AD) was found to have a positive correlation with the extent of the cholinergic loss. The septum is connected to the hippocampus via the fimbria-fomix, which carries projections from the medial septum (MS), and the vertical limb of the diagonal band of Broca. These projections are predominantly cholinergic and GABAergic. Lesions of the fimbria-fomix, or electrolytic lesions of the MS, impair hippocampal- dependent learning and memory. The purpose of this study was to investigate ability to acquire and use spatial (or non-spatial) information as well as to habituate exploratory activity over time in sham-operated, electrolytic, neuro or immunotoxic MS lesioned rats. Methods: A total of 39 male rats were used. For electrolytic lesions a stainless steel was inserted in the MS. All injections were performed stereotaxically. Rats were individually given five 3-min sessions in the open field. All experiments were approved by the Animal Care and Use Committee of the Center and were in accordance with the principles of laboratory animal care. Results: Examination of the AChE stained sections showed that after injections of 192 IgG saporin into the MS, animals exhibited significantly less AChE staining in MS and hippocampus as compared to sections obtained from control animals. The MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment, rats with immunolesions of the MS did not differ from control rats. Electrolytic lesions of the MS disrupt spatial recognition memory, rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty. The MS lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Conclusions: MS is sufficient for spatial recognition, but is not sufficient for object recognition memory, the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a suffi cient extent to impair spatial recognition memory. Therefore, the present study demonstrates dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field.
Related Products: 192-IgG-SAP (Cat. #IT-01)
How to stimulate: Basal forebrain DBS parameters to restore the attentional performance of rats with cholinergic losses
Nazmuddin M, Rao HA, Van Laar T, Sarter MF (2019) How to stimulate: Basal forebrain DBS parameters to restore the attentional performance of rats with cholinergic losses. Neuroscience 2019 Abstracts 377.10. Society for Neuroscience, Chicago, IL.
Summary: The degeneration of basal forebrain (BF) cholinergic neurons is an index of the severity of cognitive impairment in Alzheimer disease (AD) and Parkinson’s disease (PD). Moreover, in PD patients, gait and balancing deficits, and an increased propensity for falls have been attributed to cholinergic losses. Thus, Deep Brain Stimulation (DBS) of the BF has been considered a potential therapeutic intervention to improve cognition and movement control in these patients. However, efficacy of BF DBS in clinical populations has yet to be conclusively demonstrated. Likewise, the demonstration of beneficial effects of BF DBS in rodent models has been hampered by uncertainties about useful animal models and behavioral tasks and, importantly, a lack of consensus concerning DBS parameters (duration, frequency, current, intermittent versus continuous, prior and/or during task, etc.). Here we assessed various DBS parameters in rats with a partial loss of the cortical cholinergic input system. In rats, such cholinergic losses have been frequently demonstrated to impair the detection of cues during the performance of a Sustained Attention Task (SAT) and to attenuate performance recovery following a distractor challenge (dSAT). In PD patients with cholinergic losses, attentional impairments were also attributed to cortical and thalamic cholinergic losses (Kim et al., 2017). The attribution of SAT impairments to cholinergic losses is consistent with evidence showing that the detection of cues and associated attentional control parameters depend on cortical cholinergic signaling (e.g., Howe et al., 2017). Here, rats acquired the SAT, received infusions of the cholino-specific neurotoxin 192-IgG-saporin into the BF, and were implanted bilaterally with BF unipolar stimulation electrodes. Initial DBS parameters consisted of continuous high (130 Hz) versus low (20 Hz) frequency stimulation, intermittent (20-s ON at 80 Hz and 40-s OFF) stimulation, with pulse width and amplitude kept constant at 100 µs and 100 µA, respectively. We first assessed the effects of these DBS parameters on the behavior of rats in an open field space and then when administered during, or only prior to (for 1 hr), SAT and dSAT performance. Ongoing experiments indicate that these stimulation parameters are well tolerated as indicated by the absence of effects on locomotor and exploratory activity. We predict that BF DBS will be particularly effective in restoring attentional performance in the dSAT condition. If confirmed, this finding will suggest that demonstration of efficacy in patients will require measures indicating their attentional capacities in response to taxing performance challenges.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effects of an orexin-2 receptor agonist on attention in rats following loss of cortical cholinergic projections
Blumenthal SA, Maness EBL, Fadel JR, Burk JA (2019) Effects of an orexin-2 receptor agonist on attention in rats following loss of cortical cholinergic projections. Neuroscience 2019 Abstracts 418.06. Society for Neuroscience, Chicago, IL.
Summary: Deterioration to the basal forebrain cholinergic system (BFCS) is linked to age-related cognitive impairment, specifically to the pathology of Alzheimer’s disease (AD). Animals with BFCS damage perform poorly on learning, memory, and attention tasks, indicating cognitive deficits. The orexin neuropeptide system, comprised of two neuropeptides (orexin A and orexin B), has also been implicated in the cognitive decline associated with aging, likely due to the role of orexins in promoting attention. Two orexin receptor subtypes exist, orexin 1 (Ox1R) and orexin 2 (Ox2R). Studies have examined the effects of stimulation and blockage of both receptors together and Ox1R alone on attention; but no studies have examined the role of Ox2Rs in attention through the use of Ox2R agonists. Ox2Rs may be implicated in attentional processes and the loss of orexin neurons seen in age-related cognitive decline. In order to examine the role of Ox2Rs in attention following BFCS deterioration, the present study administered the Ox2R agonist, YNT-185, to rats given intrabasalis infusions of either saline (n = 12) or 192 IgG saporin (n=11), an immunotoxin which selectively destroys the BFCS. Animals received infusions of YNT-185 to the lateral ventricle (LV) in doses of 0, 1, 10, and 100nM across four separate sessions and performance was then assessed on a sustained attention task requiring discrimination between signal and non-signal trials through lever presses. The 100nM dose of YNT-185 improved attentional performance, as compared to the 0nM dose, for rats given the immunotoxin, but worsened performance for rats given saline lesions. YNT-185 may be efficacious in aiding attentional function in animals with vulnerable cholinergic systems but may lead to overexcitation for those with intact cholinergic function.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Dissociable attentional effects of dopaminergic and cholinergic lesions to the anterior cingulate cortex
Clement MK, Pimentel CS, Swaine JA, Pimentel AJ, Hutchins D, McGaughy JA (2019) Dissociable attentional effects of dopaminergic and cholinergic lesions to the anterior cingulate cortex. Neuroscience 2019 Abstracts 418.11. Society for Neuroscience, Chicago, IL.
Summary: Prior work from our lab has shown that excitotoxic lesions to the anterior cingulate cortex (ACC) impairs the ability of rats to filter certain types of distracting stimuli (Newman and McGaughy 2011). Specifically, rats with lesions of the ACC cannot filter distractors that have been made salient through pairing with reinforcement. In contrast, these same subjects can filter distracting stimuli that have not been predictive of reward. The present study investigates the effects of neuromodulator specific lesions of the same region to determine how specific neuromodulators contribute to the attentional function of ACC. Cholinergic or dopaminergic deafferentation of the ACC was achieved using either 192 IgG saporin (n=10) or dopamine transporter saporin (n=10). Lesions were restricted to the rostral portion of the area and did not spread to nearby prefrontal sub-regions e.g prelimbic cortex. After lesioning, subjects were tested in an attentional set-shifting task (Birrell and Brown 2000). While both cholinergic and dopaminergic lesions increased distractibility, these deficits were not as severe as those produced after excitotoxic lesions (n= 8). In contrast to excitotoxic lesions, both cholinergic and dopaminergic lesions also impeded formation of an attentional set. Because dopaminergic lesions produced impairments in many stages of the tasks, we hypothesized that these subjects had a more general impairment in stimulus processing. In order to address these broader processing impairments, we analyzed the data to determine whether lesioned rats showed more sensitivity to novel stimuli, or made more perseverative errors. The implications of these data for understanding the unique contributions of acetylcholine and dopamine to attentional processing in the ACC will be discussed.
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DAT-SAP (Cat. #IT-25)
SUVN-G3031, histamine H3 receptor inverse agonist preclinical evaluation for the treatment of excessive daytime sleepiness in narcolepsy
Bhyrapuneni G, Benade V, Daripelli S, Kamuju V, Shinde A, Abraham R, Nirogi R, Jasti V (2019) SUVN-G3031, histamine H3 receptor inverse agonist preclinical evaluation for the treatment of excessive daytime sleepiness in narcolepsy. Neuroscience 2019 Abstracts 502.07. Society for Neuroscience, Chicago, IL.
Summary: Numerous studies have demonstrated that brain histamine plays a crucial role in maintenance of wakefulness, attention, learning and other cognitive processes. SUVN-G3031, a potent histamine H3 receptor inverse agonist is being developed for the treatment of narcolepsy and other sleep related disorders. SUVN-G3031 is one of the lead molecules with hKi of 8.7 nM and has more than 100 fold selectivity against the related GPCRs. SUVN-G3031 exhibited desired pharmacokinetic properties and brain penetration. SUVN-G3031 blocked R-α-methylhistamine induced water intake and increased tele-methylhistamine levels in brain and cerebrospinal fluid. In the present study, SUVN-G3031 was evaluated in brain microdialysis and rodent models of electroencephalography (EEG). SUVN-G3031 was evaluated in brain microdialysis for evaluation of neurotransmitters like acetylcholine, histamine, dopamine and norepinephrine in male Wistar rats. EEG was used to evaluate the effects on sleep/ wake profile in rats and mice.A single oral administration of SUVN-G3031 produced significant increase in acetylcholine, histamine, dopamine and norepinephrine levels in the cortex. SUVN-G3031 produced no change in the dopamine levels of striatum and nucleus accumbens indicating that SUVN-G3031 may not have addiction liabilities. Narcoleptic-like sleep behavior was observed in rats injected with hypocretin-2-saporin in lateral hypothalamus. SUVN-G3031 produced significant increase in wakefulness with concomitant decrease in rapid eye movement (REM) sleep in these animals. These results are in agreement with EEG studies carried out in healthy male Wistar rats. Results from current studies provide strong evidence for the potential of SUVN-G3031 in the treatment of excessive daytime sleepiness associated with narcolepsy. First in human, Phase 1 studies for SUVN-G3031 are completed under US IND and SUVN-G3031 has shown desirable pharmacokinetic profile with safety and tolerability in healthy human volunteers. Phase 2 study for the treatment of excessive daytime sleepiness associated with narcolepsy is currently ongoing in USA.
Related Products: Orexin-B-SAP (Cat. #IT-20)