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Drug induced Memory loss

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https://www.readbyqxmd.com/read/28042943/the-impact-of-aav-capsid-specific-t-cell-responses-on-design-and-outcome-of-clinical-gene-transfer-trials-with-recombinant-aav-vectors-an-evolving-controversy
#1
Hildegund Cj Ertl, Katherine A High
Recombinant adenovirus-associated (rAAV) vectors due to their ease of construction, wide tissue tropism and lack of pathogenicity remain at the forefront for long-term gene replacement therapy. In spite of very encouraging pre-clinical results, clinical trials were initially unsuccessful; expression of the rAAV vector-delivered therapeutic protein was transient. Loss of expression was linked to an expansion of AAV capsid-specific T cell responses, leading to the hypothesis that rAAV vectors recall pre-existing memory T cells that had been induced by natural infections with AAV together with a helper virus...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28034617/cochlear-hair-cell-regeneration-after-noise-induced-hearing-loss-does-regeneration-follow-development
#2
REVIEW
Fei Zheng, Jian Zuo
Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion...
December 26, 2016: Hearing Research
https://www.readbyqxmd.com/read/28012947/the-gsk-3-inhibitor-vp2-51-produces-antidepressant-effects-associated-with-adult-hippocampal-neurogenesis
#3
Paloma Pérez-Domper, Valle Palomo, Simona Gradari, Carmen Gil, María L de Ceballos, Ana Martínez, Jose Luis Trejo
Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that has been implicated in the mechanism of action of mood stabilizers. According to the neurogenic hypothesis of depression, newborn neurons in the adult dentate gyrus are required for the antidepressant effects of certain agents. We demonstrate that administration of the GSK-3 inhibitor VP2.51 (2.5 mg/kg ip, for 3.5 weeks) increases cell proliferation (pH3(+) cells), as well as the short- and long-term survival of newborn neurons (assessed by the 24 h survival of BrdU(+) and DCX(+) neurons), while significantly increasing the commitment of cells to the granule neuron lineage (Prox1 immunoreactivity)...
December 22, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27932144/inhibition-of-jak3-and-pkc-via-immunosuppressive-drugs-tofacitinib-and-sotrastaurin-inhibits-proliferation-of-human-b-lymphocytes-in%C3%A2-vitro
#4
M N Martina, M J Ramirez Bajo, E Bañon-Maneus, D Moya Rull, N Hierro-Garcia, I Revuelta, J M Campistol, J Rovira, F Diekmann
BACKGROUND: Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. METHODS: Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27923588/autophagy-and-akt-creb-signalling-play-an-important-role-in-the-neuroprotective-effect-of-nimodipine-in-a-rat-model-of-vascular-dementia
#5
Ming Hu, Zhijuan Liu, Peiyuan Lv, Hebo Wang, Yifei Zhu, Qianqian Qi, Jing Xu
The Akt/CREB signalling pathway is involved in neuronal survival and protection. Autophagy is also likely to be involved in survival mechanisms. Nimodipine is an L-type calcium channel antagonist that reduces excessive calcium influx during pathological conditions (contributing to its neuroprotective properties). However, the potential role of nimodipine in autophagic and Akt/CREB signalling is not well understood. In addition, little is known about the relationship between autophagic and Akt/CREB signalling...
December 3, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#6
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27903275/cell-cycle-inhibition-reduces-inflammatory-responses-neuronal-loss-and-cognitive-deficits-induced-by-hypobaria-exposure-following-traumatic-brain-injury
#7
Jacob W Skovira, Junfang Wu, Jessica J Matyas, Alok Kumar, Marie Hanscom, Shruti V Kabadi, Raymond Fang, Alan I Faden
BACKGROUND: Traumatic brain injury (TBI) patients in military settings can be exposed to prolonged periods of hypobaria (HB) during aeromedical evacuation. Hypobaric exposure, even with supplemental oxygen to prevent hypoxia, worsens outcome after experimental TBI, in part by increasing neuroinflammation. Cell cycle activation (CCA) after TBI has been implicated as a mechanism contributing to both post-traumatic cell death and neuroinflammation. Here, we examined whether hypobaric exposure in rats subjected to TBI increases CCA and microglial activation in the brain, as compared to TBI alone, and to evaluate the ability of a cyclin-dependent kinase (CDK) inhibitor (CR8) to reduce such changes and improve behavioral outcomes...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27758699/design-synthesis-and-molecular-docking-studies-of-new-potential-piperazine-derivatives-as-cognition-enhancers
#8
Chhanda C Danta, Poonam Piplani
BACKGROUND: In 2016, the statistical reports stated that Alzheimer is not just memory loss but it kills and has become the 6th leading cause of death. The number of dementia patients is increasing rapidly and expected to rise to 131.5 million by 2050. Still there is not a drug candidate that can cure the cognitive deficits completely. OBJECTIVE: Series of novel piperazine derivatives have been designed, synthesized and evaluated for cognition enhancing activity...
October 14, 2016: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27720431/-common-physiological-basis-for-post-traumatic-stress-disorder-and-dependence-to-drugs-of-abuse-implications-for-new-therapeutic-approaches
#9
Pascale Gisquet-Verrier, Daniel Tolédano, Claire Le Dorze
Post-traumatic stress disorder (PTSD) and addiction to drugs of abuse are two common diseases, showing high comorbidity rates. This review presents a number of evidence showing similarities between these two pathologies, especially the hyper-responsiveness to environmental cues inducing a reactivation of the target memory leading either to re-experiencing (PTSD), or drug craving. Accordingly, PTSD and addiction to drug of abuse might by considered as memory pathologies, underlined by the same physiological process...
September 15, 2016: Thérapie
https://www.readbyqxmd.com/read/27585927/piracetam-facilitates-the-anti-amnesic-but-not-anti-diabetic-activity-of-metformin-in-experimentally-induced-type-2-diabetic-encephalopathic-rats
#10
Shruti Pandey, Debapriya Garabadu
Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals...
September 1, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27569750/circulating-t-cells-to-infliximab-are-detectable-mainly-in-treated-patients-developing-anti-drug-antibodies-and-hypersensitivity-reactions
#11
A Vultaggio, G Petroni, S Pratesi, F Nencini, D Cammelli, M Milla, F Prignano, V Annese, S Romagnani, E Maggi, A Matucci
Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developing, or not, anti-drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co-culture system of IFX-loaded dendritic cells and purified autologous CD4(+) T cells was used to detect memory T cells in 32 ADA(+) and 39 ADA(-) IFX-treated patients and control groups...
December 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27566289/rodent-sex-differences-in-disgust-behaviors-anticipatory-nausea-conditioned-to-a-context-associated-with-the-effects-of-the-toxin-licl-inhibition-of-conditioning-following-immune-stimulation-with-lipopolysaccharide
#12
Caylen J Cloutier, Martin Kavaliers, Klaus-Peter Ossenkopp
This study examined sex differences in the establishment of lithium chloride (LiCl)-induced conditioned disgust behavior (anticipatory nausea) to a distinct context in adult male and female rats. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. Twenty-nine male and 31 female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200μg/kg LPS or 0.9% (NaCl), 90min prior to i...
January 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27566203/tannoid-principles-of-emblica-officinalis-attenuated-aluminum-chloride-induced-apoptosis-by-suppressing-oxidative-stress-and-tau-pathology-via-akt-gsk-3%C3%AE-signaling-pathway
#13
Arokiasamy Justin Thenmozhi, Mathiyazahan Dhivyabharathi, Thamilarasan Manivasagam, Musthafa Mohamed Essa
ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Phyllanthus emblica Linn. or Emblica officinalis Gaertn. (Phyllanthaceae) are used in Ayurveda, Siddha, Unani, Arabic, Tibetan and various other folk medicinal systems to promote intelligence and memory. Recent study from our lab indicated the neuroprotective effect of tannoids principles of Emblica officinalis (EoT) against memory loss caused by aluminum chloride (AlCl3) intoxication through attenuating acetylcholine esterase activity and the expression of amyloid β protein biosynthesis related markers...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27509875/fenamate-nsaids-inhibit-the-nlrp3-inflammasome-and-protect-against-alzheimer-s-disease-in-rodent-models
#14
Michael J D Daniels, Jack Rivers-Auty, Tom Schilling, Nicholas G Spencer, William Watremez, Victoria Fasolino, Sophie J Booth, Claire S White, Alex G Baldwin, Sally Freeman, Raymond Wong, Clare Latta, Shi Yu, Joshua Jackson, Nicolas Fischer, Violette Koziel, Thierry Pillot, James Bagnall, Stuart M Allan, Pawel Paszek, James Galea, Michael K Harte, Claudia Eder, Catherine B Lawrence, David Brough
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes...
2016: Nature Communications
https://www.readbyqxmd.com/read/27498773/dl0410-a-novel-dual-cholinesterase-inhibitor-protects-mouse-brains-against-a%C3%AE-induced-neuronal-damage-via-the-akt-jnk-signaling-pathway
#15
Dan Zhou, Wei Zhou, Jun-Ke Song, Zhang-Ying Feng, Ran-Yao Yang, Song Wu, Lin Wang, Ai-Lin Liu, Guan-Hua Du
AIM: 1,1'-([1,1'-Biphenyl]-4,4'-diyl)bis(3-(piperidin-1-yl)propan-1-one)dihydrochloride (DL0410) is a novel synthetic dual acetylcholinesterase (AChE)/butyrocholinesterase (BuChE) inhibitor, which has shown a potential therapeutic effect on Alzheimer's disease (AD). In this study we examined whether DL0410 produced neuroprotective effects in an AD cellular model and an Aβ1-42-induced amnesia mouse model. METHODS: The in vitro inhibitory activities against AChE and BuChE were estimated using Ellman's assay...
November 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27472873/streptozotocin-induces-mild-cognitive-impairment-at-appropriate-doses-in-mice-as-determined-by-long-term-potentiation-and-the-morris-water-maze
#16
Dong Li, Yan Huang, Bin Cheng, Jie Su, Wen-Xia Zhou, Yong-Xiang Zhang
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and effective therapeutic drugs in the clinic are still lacking. Ideally, AD progression could be stopped at an early stage, such as at the mild cognitive impairment (MCI) stage. MCI refers to the clinical condition between normal aging and dementia. Patients with MCI experience memory loss but do not meet the criteria for the diagnosis of clinically probable AD. However, few MCI animal models have been established. Here, we used in vivo long-term potentiation (LTP) recording and the Morris water maze (MWM) to evaluate the effects of intracerebroventricular injection of streptozotocin (ICV-STZ) in mice...
July 27, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27467732/ketamine-protects-gamma-oscillations-by-inhibiting-hippocampal-ltd
#17
Lanting Huang, Xiu-Juan Yang, Ying Huang, Eve Y Sun, Mu Sun
NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks...
2016: PloS One
https://www.readbyqxmd.com/read/27445731/multiple-drug-treatments-that-increase-camp-signaling-restore-long-term-memory-and-aberrant-signaling-in-fragile-x-syndrome-models
#18
Catherine H Choi, Brian P Schoenfeld, Aaron J Bell, Joseph Hinchey, Cory Rosenfelt, Michael J Gertner, Sean R Campbell, Danielle Emerson, Paul Hinchey, Maria Kollaros, Neal J Ferrick, Daniel B Chambers, Steven Langer, Steven Sust, Aatika Malik, Allison M Terlizzi, David A Liebelt, David Ferreiro, Ali Sharma, Eric Koenigsberg, Richard J Choi, Natalia Louneva, Steven E Arnold, Robert E Featherstone, Steven J Siegel, R Suzanne Zukin, Thomas V McDonald, Francois V Bolduc, Thomas A Jongens, Sean M J McBride
Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27445088/neuroprotection-against-glutamate-induced-excitotoxicity-and-induction-of-neurite-outgrowth-by-t-006-a-novel-multifunctional-derivative-of-tetramethylpyrazine-in-neuronal-cell-models
#19
Daping Xu, Haiyun Chen, Shinghung Mak, Shengquan Hu, Karl W K Tsim, Yuanjia Hu, Yewei Sun, Gaoxiao Zhang, Yuqiang Wang, Zaijun Zhang, Yifan Han
Alzheimer's disease is a progressive neurodegenerative disorder, characterized by irreversible impairment of memory and cognitive function. The exact causes of Alzheimer's disease still remain unclear and current single target drugs could only offer limited therapeutic effect to the patients. We have previously reported that T-006, a promising anti-Alzheimer's compound derived from Chinese medicinal component tetramethylpyrazine, might protect neurons through inhibiting the overproduction of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS)...
October 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27305963/e-pharmacophore-based-virtual-screening-to-identify-gsk-3%C3%AE-inhibitors
#20
Pradeep Natarajan, Vani Priyadarshini, Dibyabhaba Pradhan, Munikumar Manne, Sandeep Swargam, Hema Kanipakam, Vengamma Bhuma, Umamaheswari Amineni
Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase which has attracted significant attention during recent years in drug design studies. The deregulation of GSK-3β increased the loss of hippocampal neurons by triggering apoptosis-mediating production of neurofibrillary tangles and alleviates memory deficits in Alzheimer's disease (AD). Given its role in the formation of neurofibrillary tangles leading to AD, it has been a major therapeutic target for intervention in AD, hence was targeted in the present study...
October 2016: Journal of Receptor and Signal Transduction Research
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