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Improvements of cognitive function by focused ultrasound associated with adult hippocampal neurogenesis in immunotoxin 192-Saporin rat model of cholinergic degeneration
Kong C, Shin J, Lee J, Koh C, Sim J, Na Y, Chang W, Chang J (2018) Improvements of cognitive function by focused ultrasound associated with adult hippocampal neurogenesis in immunotoxin 192-Saporin rat model of cholinergic degeneration. Neuroscience 2018 Abstracts 174.27 / JJJ31. Society for Neuroscience, San Diego, CA.
Summary: Introduction: Alzheimer’s disease is irreversible, progressive neurodegenerative disorder that destroys memory and cognitive function. Recently, focused ultrasound (FUS) has been demonstrated that FUS-mediated BBB opening induces an increase in hippocampal neurogenesis in adult rodents. In this study, we investigated the effects of FUS on memory and cognitive function after 192 IgG-saporin lesion. Materials and Methods: The present study utilized adult male Sprague-Dawley rats (200-250 g). Animals were divided into the three groups: Sham group (PBS injection), Lesion group (saporin injection), FUS group (saporin + FUS treatment). Lesion groups were injected bilaterally into the lateral ventricle. Rats were sonicated using a single-element transducer 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. BrdU was intraperitoneally injected two times per day for 4 consecutive days starting 24 hours after sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training. Results: In the water maze test, the FUS groups were significantly increased in number of crossing and platform zone, compared to the lesion group. We confirmed that the number of BrdU+, DCX+, and NeuN+ were significantly increased in the dentate gyrus following FUS sonication, compared to the lesion groups. Also, we found that the expression level of BDNF and TrkB increased in FUS group. Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. Therefore, this provides evidence that the behavior changes may be mediated by increased acetylcholine activity and neuronal plasticity. Furthermore, FUS may represent a promising treatment for neurodegenerative disease, including Alzheimer’s disease because neurogenesis is associated with memory and cognitive function.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Lifespan and cholinergic changes in cognitive flexibility in rats
Cammarata C, DeRosa ED, Anderson AK (2018) Lifespan and cholinergic changes in cognitive flexibility in rats. Neuroscience 2018 Abstracts 512.05 / GGG8. Society for Neuroscience, San Diego, CA.
Summary: The ability to update one’s mental schemas in order respond flexibly and adaptably – i.e. cognitive flexibility – is crucial to navigating a dynamic environment. Proactive interference (PI) is a phenomenon wherein prior memory impedes the formation of new memories for similar information, biasing behavior toward no-longer-relevant schemas. Thus, overcoming PI is an important aspect of cognitive flexibility. PI is exacerbated during aging, and in turn contributes to age-related deficits in cognitive flexibility. In young animals and young adult humans, resolution of PI has been found to rely on neuromodulatory activity via Acetylcholine (ACh), and ACh levels are known to decline in aging, however it has yet to be demonstrated whether these age-related changes in ACh directly contribute to age-related increase in PI. Here, we first compared PI resolution in middle-aged (13 months, n = 8) and old (23 months, n= 11) male Long Evans rats, finding that old animals were more inefficient in resolving PI when compared to the middle-aged animals. Furthermore we performed cholinergic deafferentation, with the immunotoxin 192-IgG saporin (SAP; 0.2 µl of 0.3 µg/µl dissolved in sterile phosphate buffered sale in each of four locations targeting bilateral anterior and posterior basal forebrain), in our older rats (N= 5 SAP and N=6 Sham) which had no effect on the floor performance of older rats. This suggests that the inability to resolve PI seen in the aged rats may be due to already-depleted levels of ACh. We are currently collecting local field potential data in the prelimbic and posterior parietal cortices in behaving older and younger rats and will combine this with central administration of muscarinic cholinergic pharmacology to continue to examine age-related changes in the cortical dynamics that support cognitive flexibility. Based on prior findings in our laboratory examining similar attentional flexibility, we predict the young animals will demonstrate increased beta band LFP activity in the posterior parietal cortex, and potentially increased beta coherence between prefrontal and posterior parietal cortices, related to successful resolution of PI. We expect such activity to be mitigated by cholinergic antagonists and in the older animals.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Lacrimal gland denervation alters tear protein composition and impairs ipsilateral eye closures and corneal nociception
Hegarty DM, David LL, Aicher SA (2018) Lacrimal gland denervation alters tear protein composition and impairs ipsilateral eye closures and corneal nociception. Invest Ophthalmol Vis Sci 59:5217-5224. doi: 10.1167/iovs.18-25267
Objective: To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes.
Summary: Denervation of the lacrimal gland causes long-lasting hypoalgesia, impairs the blink response, and alters tear proteins.
Usage: 192-IgG-SAP (5 μL, 0.5 μg/μL) was microinjected into the left extraorbital lacrimal gland. In a separate group, 192-IgG-SAP was applied directly and unilaterally to the corneal surface.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neuropharmacology of attention
Burk JA, Blumenthal SA, Maness EB (2018) Neuropharmacology of attention. Eur J Pharmacol 835:162-168. doi: 10.1016/j.ejphar.2018.08.008
Objective: This review focuses on the knowledge gained about neurotransmitter systems with respect to attentional processing, with emphasis on the functions mediated within the medial prefrontal cortex.
Summary: Future research needs to facilitate a better comprehension of the neural circuitry engaged by different subcategories of attention. Such information will be useful in allowing for more targeted treatments for conditions characterized by attentional deficits.
Usage: Several citations using 192-IgG-SAP;. The specific role of ACh in attentional function can be examined with lesions to cholinergic inputs to the mPFC, using the immunotoxin 192 immunoglobulin G (IgG) saporin. Increases in mPFC ACh efflux related to attention are no longer present following cholinergic lesions. These cholinergic lesions lead to severe deficits in performance on both sustained attention and 5CSRTT-related tasks.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Molecular, cellular and circuit basis of cholinergic modulation of pain
Naser PV, Kuner R (2018) Molecular, cellular and circuit basis of cholinergic modulation of pain. Neuroscience 387:135-148. doi: 10.1016/j.neuroscience.2017.08.049
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic modulation of spatial learning, memory and navigation.
Solari N, Hangya B (2018) Cholinergic modulation of spatial learning, memory and navigation. Eur J Neurosci 48:2199-2230. doi: 10.1111/ejn.14089
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
The hot ‘n’ cold of cue-induced drug relapse
Pitchers KK, Sarter M, Robinson TE (2018) The hot ‘n’ cold of cue-induced drug relapse. Learn Mem 25:474-480. doi: 10.1101/lm.046995.117
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate
Lelkes Z, Abdurakhmanova S, Porkka-Heiskanen T (2018) Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate. J Sleep Res 27:e12605. doi: 10.1111/jsr.12605
Objective: Discover to what extent the cholinergic versus non‐cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate.
Summary: Destruction of the basal forebrain cholinergic neurons did not abolish the wake‐enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate.
Usage: 0.23 μg 192 IgG‐SAP was administered into the basal forebrain.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Effects of cholinergic lesions and cholinesterase inhibitors on aromatase and estrogen receptor expression in different regions of the rat brain
Li J, Rao D, Gibbs RB (2018) Effects of cholinergic lesions and cholinesterase inhibitors on aromatase and estrogen receptor expression in different regions of the rat brain. Neurosci 384:203-213. doi: 10.1016/j.neuroscience.2018.05.033
Objective: To determine if effects of cholinergic inputs on synaptic plasticity and neuronal function are mediated by effects on local estrogen production or ER expression.
Summary: Selectively destroying cholinergic projections to the hippocampus had little effect on ARO and ER expression in many regions of the rat brain.
Usage: Rats received intraseptal injections of 2.0 ml (0.2 mg/ml) or icv injections of 0.4 mcg. Lesions resulted in loss of ChAT-positive cells in the septum, and ChAT activity in the hippocampus. Septal infusions eliminated most of the ChAT-IR cells in MS; ChAT activity in hippocampus also significantly decreased. ChAT activity in the frontal cortex was not significantly affected.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Improvements in cognitive function after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis.
Shin J, Kong C, Lee J, Na YC, Chang WS, Chang JW (2018) Improvements in cognitive function after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis. FENS 2018 Abstracts C038. Federation of European Neuroscience Societies, Berlin, Germany.
Summary: Introduction: Alzheimer’s disease is irreversible and progressive neurodegenerative disorder that destroys memory and cognitive function. Recently, focused ultrasound (FUS) has been demonstrated that FUS- mediated BBB opening induces an increase in hippocampal neurogenesis in adult rodents. In this study, we investigated the effects of FUS on memory and cognitive function after 192 IgG-saporin lesioning. Materials and Methods: The present study utilized adult male Sprague-Dawley rats (200-250 g). Animals were divided into the three groups: Sham group (PBS injection), Lesion group (saporin injection), FUS group (saporin + FUS treatment). Lesion groups were injected bilaterally into the lateral ventricle. Rats were sonicated by using a single-element transducer with microbubble. The acoustic parameters for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training. Results: In the water maze test, the FUS groups were significantly increased in number of crossing and platform zone, compared to the lesion group. We confirmed that the number of BrdU+, DCX+, and NeuN+ were significantly increased in the dentate gyrus following FUS sonication, compared to the lesion groups. Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. These provided evidences indicate that reason of the behavior change may be induced by increase of acetylcholine activity and neuronal plasticity.
Related Products: 192-IgG-SAP (Cat. #IT-01)