Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats

Abstract

Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats’ motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline.

A Systematic Review of the Dietary Choline Impact on Cognition from a Psychobiological Approach: Insights from Animal Studies

“…Finally, prenatal and postnatal choline supplementation has been reported to attenuate the vulnerability to the adult insult induced by the NMDA receptor antagonist MK-801 which is used to model schizophrenia-like cognitive impairments. A perinatal supplementation period (ED10-PND2) prevented the object recognition memory deficits induced by low doses of MK-801 administered after the familiarization session during the 3 h delay before the retention tests session [33]. Likewise, periadolescent (PND 25-50) choline supplementation prevented the object recognition memory impairment induced by MK-801 administration in the offspring of rats subjected to gestational stress [44].…”

“…The studies we have investigated have applied a bulk of procedures for assessing cognition and emotion in combination with other processes, such as motor performance [33,50] and social interaction in rodents [37,40]. Although it is difficult to dissociate the processes involved in a given procedure and the same task might be modified in order to explore different processes, there are specialized behavioral tests such as the rotarod intended for evaluation of motor coordination and balance [73], the open-field [74], the elevated plus maze [75] and the forced swim test [76] for emotionality/anxiety and the three-chamber test for social interaction.…”

“…Although it is difficult to dissociate the processes involved in a given procedure and the same task might be modified in order to explore different processes, there are specialized behavioral tests such as the rotarod intended for evaluation of motor coordination and balance [73], the open-field [74], the elevated plus maze [75] and the forced swim test [76] for emotionality/anxiety and the three-chamber test for social interaction. Amongst the studies revised, although the rotarod has only been applied by Pacelli et al [50] and the three-chamber test has only been used in a mice model of autism [37], the use of tests assessing emotionality or anxiety such as the open field or the elevated plus maze has been more frequently applied [37] and in nearly all the cases combined with cognitive tasks [28,33,46,56,61].…”

“…The main procedural difference between the groups lies in the retention period applied. Whilst de Brugada and collaborators were interested in long-term recognition memory and they applied 24-48 h delays between the familiarization and testing sessions [29,31,34,41], Kennedy et al [32,40] used 1 and 6 h, and Glenn's group used shorter delays ranging from 3 h [33] to 20 min [44].…”

1MeTIQ and olanzapine, despite their neurochemical impact, did not ameliorate performance in fear conditioning and social interaction tests in an MK-801 rat model of schizophrenia

“…MK-801 is an NMDA receptor antagonist and is commonly used in animal models to mimic schizophrenialike behaviors [9]. MK-801 is reported to disturb working memory, memory consolidation, social interaction, contextual fear conditioning and prepulse inhibition [10][11][12][13][14][15].…”