Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats Following Intra-generational Protein Malnutrition

Abstract

Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed.

Neonatal Lipopolysaccharide Infection Causes Demyelination and Behavioral Deficits in Adult and Senile Rat Brain

“…The histological data validating the loss of myelin by neonatal LPS exposure very well exemplifies the decline in motor behavior. The rotarod task [22,33,34] , the notched balance beam test [35], and the grip strength test [21,36] have been useful in study of motor impairments following CNS injury. We have also assessed the impact of demyelination on the motor activity of rats using grip strength and rotarod test.…”

“…Grip Strength Test Forelimb neuromuscular strength of control and LPS-treated animals ( n = 12) was assessed by using Grip strength meter (Columbus, OH, USA) as described by Naik et al [21] . The animal was handled with its tail and placed carefully over the pull bar assembly/metallic grid (76 × 250 mm) of the instrument and allowed to hold the grid through its forelimbs.…”

Effects of maternal low‐protein diet on parameters of locomotor activity in a rat model of cerebral palsy

“…Clinical and experimental studies have established that undernutrition damages the neurodevelopment, physical growth parameters and brain structure (Akitake et al, 2015;Naik et al, 2015). Both CP and undernutrition may affect the maintenance of muscle mass (Marcuzzo et al, 2008;Toscano et al, 2008).…”

Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring

“…Maternal protein energy malnutrition (PEM) is known to induce cognitive impairment as well as deficits in learning and memory in the adult progeny [88]. In rodents, prenatal exposure to maternal LP diets induces structural deficits in brain architecture caused by alterations in neuronal proliferation and differentiation, awry dendritic arborizations, differences in myelination, and impairments in synaptogenesis [4] that translate into long-term indelible adverse effects on cognition and behavioral abnormalities [71, 89].…”

“…Prenatal PEM results in cognitive and behavioral inflexibility as well as inadaptability in adult rats as assessed by conditioned taste aversion (CTA), performance of differential reinforcement of low rates (DRL) operational tasks, and reversal learning in a T-maze [5]. Postnatal PEM also causes somatosensory and motor deficits in rats when subjected a standard battery of paradigms that include determination of righting reflex, cliff avoidance test, negative geotaxis, and forelimb grip-strength tests [88]. In light of the aforementioned effects of prenatal PEM on behavior as well as somatosensory and motor deficits, there is significant evidence that prenatal PEM causes fluxes in levels of the neurotransmitters and the functioning of the neurotransmitter systems [107].…”