Purpose: Amphetamine (AMPH) increases locomotor activities in animals, and the locomotor response to AMPH is further modulated by caloric deficits such as food deprivation and restriction. The increment in locomotor activity regulated by AMPH-caloric deficit concomitance can be further modulated by varying feeding schedules (e.g., acute and chronic food deprivation and acute feeding after chronic food deprivation). However, the effects of different feeding schedules on AMPH-induced locomotor activity are yet to be explicated. Here, we have explored the stimulatory responses of acutely administered D-amphetamine in locomotion under systematically varying feeding states (fed/sated and food deprivation) and schedules (chronic and acute) in zebrafish larvae.
Method: We exposed wild-type and transgenic [Tg(mnx1:GCaMP5)] zebrafish larvae to 0.7 µM concentration of AMPH and measured swimming activity and spinal motor neuron activity in vivo in real time. The analysis involved time-elapsed and cumulative manner pre- and post-AMPH treatment in four different caloric states including acute and chronic schedules of feeding and hunger. Both locomotor and motor neuron activities were compared in all four states in both fish lines.
Findings: Our results show that locomotion and motor neuron activity increased in both chronic and acute food deprivation post-AMPH treatment cumulatively. A steady increase in locomotion was observed in acute food deprivation compared to an immediate abrupt increase in chronic food-deprivation state. The ad libitum-fed larvae exhibited a moderate increase both in locomotion and motor neuron activity. Conversely to all other caloric states, food-sated (acute feeding after chronic food deprivation) larvae moved moderately less and exhibited a mild decrease in motor neuron activity after AMPH treatment.
Conclusion: These results reveal the importance of cohesive effects of feeding schedule and AMPH treatment by revealing the changes in stimulatory characteristics of AMPH on locomotion and motor neuron activity in acute and chronic feeding states.
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http://dx.doi.org/10.1002/brb3.70173 | DOI Listing |
Alzheimers Dement
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Stem Cells & Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
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Shenzhen Bay Laboratory, Shenzhen, Guandong, China.
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German Center for Neurodegenerative Diseases (DZNE), Munich, Bavaria, Germany.
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View Article and Find Full Text PDFAlzheimers Dement
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Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: Emerging evidence support the notion that loss of splicing repression by TDP-43, an RNA binding protein that was first implicated in ALS-FTD, underlies their pathogenesis. Previously, we showed that delivery of an AAV9 vector at early postnatal day expressing a fusion protein, termed CTR comprised of the N-terminal region of TDP-43 and an unrelated splicing repressor termed RAVER1 complemented the loss of TDP-43 in mice lacking TDP-43 in spinal motor neurons (ChAT-IRES-Cre;tardbp mice). To translate this potential therapeutic strategy to the clinic, it will be important to demonstrate benefit of such AAV delivery of CTR to motor neurons in adult mice.
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