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Placenta-derived mesenchymal stem cells facilitate neural and cognitive recovery in dementia rat model.
Cho J, Lee J, Jeong D, Kim H, Chang W, Moon J, Chang J (2016) Placenta-derived mesenchymal stem cells facilitate neural and cognitive recovery in dementia rat model. Neuroscience 2016 Abstracts 38.10 / G29. Society for Neuroscience, San Diego, CA.
Summary: Introduction: Dementia is a term that encompasses various types of neurodegenerative diseases of the brain that cause a gradual decline in mental abilities. Loss of cholinergic neurons in the brain cholinergic system including the hippocampus is a hallmark of many dementia cases. In this study, we report the therapeutic effects of administration of human placenta-derived mesenchymal stem cells (pMSCs) in dementia model Sprague-Dawley (SD) rats using two different cell injection methods: intracerebroventricular (ICV) and intravenous (IV) injections. Methods: Dementia modeling was carried out by intraventricular injection of 192 IgG saporin, which causes lesion of cholinergic neurons. Fifty male SD rats were divided into four groups: normal (n=9), lesion (n=9), ICV (n=12) and IV (n=12). All rats were then subject to Morris water maze test and subsequent immunostaining analyses using markers for human cytoplasm, acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and microglial cells at the hippocampus. Results: Lesioned rats showed poor performance in the Morris water maze test compared to the normal rats. Both ICV and IV pMSC administration allowed significant cognitive recovery compared to the lesioned rats. AChE was also significantly recovered back to normal levels at the hippocampus in rats injected with pMSCs post-lesion. ChAT did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Stem cell count showed a significantly greater number of pMSCs at the hippocampal dentate gyrus in IV group rats compared to ICV group rats. Number of microglial cells increased in lesioned rats, and was significantly reduced back to normal levels after pMSC injection. Discussion: Our results demonstrate that injection of pMSCs facilitates recovery of cholinergic neuronal population and function, as well as cognitive behavior. The mechanism through which such recovery happens does not seem to be direct differentiation of injected pMSCs into cholinergic neurons, but rather seems to be through paracrine effects that resemble microglial function. Further research will be necessary for elucidation of the exact mechanisms involved and establishment of optimal parameters for successful cell homing. Acknowledgements: This study was supported by the grant from the Yonsei University Future-leading Research Initiative (Yonsei Challenge) of 2015 (2015-22-0137) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1C1A1A02036851).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neuronal and glial changes in rat hippocampal formation after cholinergic deafferentation
Paban V, Valable S, Baril N, Gilbert V, Chambon C, & Alescio-Lautier B (2016) Neuronal and glial changes in rat hippocampal formation after cholinergic deafferentation. J Biomol Res Ther 5(3):1000147. doi: 10.4172/2167-7956.1000147
Summary: The effects of cholinergic insult were studied in the hippocampal formation of cholinergic lesioned rats at metabolic and cellular levels by in vivo nuclear magnetic resonance spectrometry and immuno-histochemical approaches.
Usage: Cholinergic deafferentation was induced by injection of the cholinergic immunotoxin 192-IgG-SAP into the medial septum (37.5 ng/side).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Reducing falls in Parkinson’s disease: interactions between donepezil and the 5‐HT6 receptor antagonist idalopirdine on falls in a rat model of impaired cognitive control of complex movements
Kucinski A, de Jong IEM, Sarter M (2017) Reducing falls in Parkinson’s disease: interactions between donepezil and the 5‐HT6 receptor antagonist idalopirdine on falls in a rat model of impaired cognitive control of complex movements. Eur J Neurosci 45:217-231.. doi: 10.1111/ejn.13354
Objective: To assess the effects of treatment on MCMCT performance and attention in DL rats. The combined treatment of the acetylcholinesterase inhibitor donepezil and the 5-HT6 receptor antagonist idalopirdine (Lu AE58054) was use because it has been reported to exhibit synergistic pro-cholinergic activity in rats and improved cognition in patients with moderate Alzheimer’s disease.
Summary: This treatment may reduce fall propensity in patients.
Usage: 192-IgG-SAP aCSF infused bilaterally (120 ng/uL; 0.5 uL/hemisphere).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat.
Vierck C, Yezierski R, Wiley R (2016) Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat. Neuroscience 319:23-34. doi: 10.1016/j.neuroscience.2016.01.038
Objective: There is a large amount of research on the involvement of cholinergic mechanisms on spinal transmission of pain signals, indicating that cholinergic agonists can attenuate this kind of pain. In contrast, some studies have shown affective reactions to pain are suppressed by cholinergic antagonists. The authors investigated the disagreement between reflexive and affective reactions.
Summary: Lesioned rats displayed decreased escape from thermal stimulation, as well as loss of the normal hyperalgesic effect of sound stress. Results indicate that the basal forebrain cholinergic system plays a role in central processing of pain.
Usage: Administration of 192-IgG-SAP with a 4-μg injection into the left lateral ventricle of rats. Animals were tested in temperature escape and sound stress models.
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Featured Article: Cerebral cholinergic lesion reduces operant responses to unpleasant thermal stimuli
Wiley RG (2016) Featured Article: Cerebral cholinergic lesion reduces operant responses to unpleasant thermal stimuli. Targeting Trends 17(2)
Related Products: 192-IgG-SAP (Cat. #IT-01)
Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets.
Wang L, Conner J, Nagahara A, Tuszynski M (2016) Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets. Proc Natl Acad Sci U S A 113:2750-2755. doi: 10.1073/pnas.1514682113
Summary: Rehabilitation is often prescribed after brain injury, but the basis for how training can influence brain plasticity and recovery is unclear. In this study, the authors show that intense rehabilitation training after focal brain injury drives significant structural changes in brain cells located adjacent to the injury. Importantly, a key brain modulatory system, the basal forebrain cholinergic system, is required for enabling rehabilitation to impact brain structure. Rats underwent cholinergic ablations by injecting 192-IgG-Saporin (Cat. #IT-01) into the nucleus basalis (0.2-0.25 mcl of 0.375 mg/ml solution in artificial CSF). Damage to the cholinergic system, which can occur naturally during aging, completely blocks brain plasticity mediated by rehabilitation and significantly attenuates functional recovery. These results provide new insights into how rehabilitation may promote recovery and suggest that brain cholinergic systems may be a possible therapeutic target for influencing recovery.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain.
Vazquez-DeRose J, Schwartz M, Nguyen A, Warrier D, Gulati S, Mathew T, Neylan T, Kilduff T (2016) Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain. Brain Struct Funct 221:923-940. doi: 10.1007/s00429-014-0946-y
Summary: The basal forebrain (BF) is one of the regions receiving excitatory input from orexin neurons. The authors investigated the hypothesis that orexin antagonists induce sleep at least in part by interfering with the facilitation of BF neurons. Rats received bilateral 500-ng injections of 192-IgG-SAP (Cat. #IT-01) into the BF. Lesioned animals displayed no abnormal responses to a benzodiazepine agonist or vehicle. An orexin antagonist, however, was less effective than the control at inducing sleep in lesioned rats.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task.
Köppen J, Stuebing S, Sieg M, Blackwell A, Blankenship P, Cheatwood J, Wallace D (2016) Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task. Behav Brain Res 299:97-104. doi: 10.1016/j.bbr.2015.11.021
Summary: The memory impairments experienced in neurodegenerative disorders such as Alzheimer’s disease have been well documented. One theory attributes these impairments to the loss of cholinergic basal forebrain neurons, a hallmark of Alzheimer’s disease. Some patients experience a retrograde amnesia, in which older memories are relatively stable and more recent memories are frequently lost. The temporal relationship of memories to disease onset has not been definitively established. In this work the authors administered either 150 ng or 200 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum of rats. Using a string-pulling task, a model for temporal learning was established. The results indicate that cholinergic projections originating in the medial septum are involved in long-term memory retrieval, and that loss of these neurons does not create a temporal type of amnesia.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neuroteratology and animal modeling of brain disorders
Archer T, Kostrzewa RM (2016) Neuroteratology and animal modeling of brain disorders. Curr Top Behav Neurosci 29:1-40. doi: 10.1007/7854_2015_434
Summary: This work covers development and use of the neurotoxins that are most commonly used as neuroteratologic agents – producing permanent, lifelong destruction of specific groups of neurons. Saporin conjugates are discussed, in terms of animal models of human neurodegenerative, neuropsychiatric, and neurological conditions. In contrast to 192 IgG-SAP treatment of adult rats,which also destroys cerebellar Purkinje cells, perinatal 192 IgG-saporin spares Purkinje cells which have a lower expression of p75NGF
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The effect of nucleus basalis magnocellularis deep brain stimulation on memory function in a rat model of dementia.
Lee J, Jeong D, Lee J, Chang W, Chang J (2016) The effect of nucleus basalis magnocellularis deep brain stimulation on memory function in a rat model of dementia. BMC Neurol 16:6. doi: 10.1186/s12883-016-0529-z
Objective: Deep brain stimulation (DBS) is the application of electrical impulses to specific parts of the brain for treating disorders such as Parkinson’s disease, chronic pain, and obsessive-compulsive disorder. This study investigated whether stimulation of brain structures associated with memory can enhance cognitive function.
Summary: Results indicate that DBS has beneficial effects on consolidation and retrieval of visuospatial memory.
Usage: The authors lesioned the basal forebrain of rats through bilateral injections totaling 5 μg of 192-IgG-SAP into the lateral ventricle. Animals then received DBS to the nucleus basalis magnocellularis and were tested in a Morris water maze task.
Related Products: 192-IgG-SAP (Cat. #IT-01)